ETHANOL
ETHANOL
CASRN: 64-17-5
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~AAAoVaqOB:1
Human Health Effects:
Evidence for Carcinogenicity:
A4; Not classifiable as a
human carcinogen.
Human Toxicity Excerpts:
At 20-99 mg ethyl alcohol/100
ml blood: Impaired sensory function: 1. Reduced visual acuity (flicker-fusion
test). 2. Decr sense of smell and taste. 3. Elevated threshold for pain: a. Decr
sensitivity of cornea of eye. b. Decr sensitivity to local heating of skin. B.
Muscular incoordination: 1. Spontaneous and induced nystagmus. 2. Decr
steadiness while standing (Romberg test). 3. Impaired performance on tests of
skill (Ring test, finger-to-finger test, target practice, typing). 4. Impairment
of ability to drive an automobile. C. Changes in mood, personality, and
behavior: 1. Dizziness. 2. Reduced sense of fatigue. 3. Mild euphoria. 4. Self
satisfaction. 5. Release of inhibitions. 6. Loud, profuse speech. D. Impaired
mental activity: 1. Subtraction test. 2. Reading comprehension tests.
At 100-199 mg ethyl
alcohol/100 ml/dl/ blood: A. Staggering gait. B. Marked impairment on mental
tests. C. Marked impairment of driving ability. D. Lengthened reaction time. At
200-299 mg/100 ml/dl/: A. Nausea and vomiting. B. Diplopia. C. Marked ataxia. D.
Extreme clumsiness. At 300-399 mg/100 ml/dl/: A. Hypothermia. Cold, clammy skin.
B. Loss of ability to speak. C. Amnesia. D. Anesthesia. E. Heavy breathing.
The threshold level that
impairs skill in automobile driving is about 35 mg/100 ml/dl/ ethyl alcohol in
blood. Blood levels greater than 400 mg/100 ml/dl/ produce deep coma and
possibly death. If the coma persists for 8 to 10 hr, shock and circulatory
collapse may develop.
In severe acute intoxication
pt is stuporous or comatose. Skin is cold & clammy, body temp is low,
respirations ... slow & noisy, pupils may be normal or dilated ... heart
rate accelerated. If this condition persists ... 8 or 10 hr, hypostatic
pneumonia or incr intracranial pressure may ensue.
... A splash on human eye
causes immediate burning and stinging discomfort with reflex closure of the
lids.
Alcohol vapor exposure at
sufficiently high concn may cause prompt stinging and watering of the eyes, but
there appear to be no reports of eye injury from industrial exposure to alcohol
vapors. Human volunteers exposed to alcohol vapor have observed at concn of 0.7
to 1% vapor in air the smell of alcohol was at first almost unbearable, although
unpleasant later, and that the eyes began to burn with incr intensity after
several min. ... A vapor concn of 0.25% had no notable effect on the eyes.
... 4 cases of chronic
alcoholic patients who developed oscillopsia (illusory movement of the
environment) with downbeat nystagmus, associated with ataxia of gait and
cerebellar atrophy /were reported/.
... FETAL ALCOHOL SYNDROME ...
THE ABNORMALITY CONSISTS IN CNS DYSFUNCTION (SUCH AS LOW IQ AND MICROCEPHALY),
SLOWNESS IN GROWTH, A CHARACTERISTIC CLUSTER OF FACIAL ABNORMALITIES (SUCH AS
SHORT PALPEBRAL FISSURES, HYPOPLASTIC UPPER LIP, AND SHORT NOSE), AND A VARIABLE
SET OF MAJOR AND MINOR MALFORMATIONS. THESE FEATURES MAY BE DUE, AT LEAST IN
PART, TO A DIRECT ACTION OF ETHANOL TO INHIBIT EMBRYONIC CELLULAR PROLIFERATION
EARLY IN GESTATION. ... CHILDREN WITH THE FETAL ALCOHOL SYNDROME HAVE A GREATLY
INCR SUSCEPTIBILITY TO BOTH LIFE THREATENING AND MINOR INFECTIOUS DISEASES. SUCH
CHILDREN HAVE EXTENSIVE IMPAIRMENT OF THEIR IMMUNE SYSTEM ... .
SURAL NERVES OF PT WITH
DIFFERENT SIGNS OF ALCOHOLIC NEUROPATHY WERE STUDIED BY ELECTRON MICROSCOPY.
MYELINATED & UNMYELINATED FIBERS SHOWED DEGENERATIVE CHANGES OF THE
WALLERIAN TYPE. IMBALANCE IN DEGENERATIVE & REGENERATIVE PROCESSES SEEM TO
BE THE BASIS OF CHRONIC PARTIAL DENERVATION.
... HEMATOLOGIC EFFECTS ...
ALCOHOL INTERFERES WITH SEVERAL ASPECTS OF FOLATE METABOLISM AND TRANSPORT, AS
WELL AS WITH ITS NORMAL PATTERN OF STORAGE AND RELEASE FROM THE LIVER. ... OTHER
EFFECTS, SUCH AS THROMBOCYTOPENIA AND VACUOLIZATION OF PRECURSORS OF RED &
WHITE CELLS ... THERE IS ALSO A DEPRESSION OF LEUKOCYTE MIGRATION INTO INFLAMED
AREAS WHICH MAY PARTLY ACCOUNT FOR POOR RESISTANCE OF ALCOHOLICS TO INFECTION.
Alcohol ingestion impairs
glottic reflexes, and alcoholics are predisposed to pneumonias and lung
abscesses from aspiration of oropharyngeal bacteria. Alcohol intoxication also
incr the frequency of sleep apnea and may result in respiratory failure from
oversedation.
Acute alcohol ingestion can
lead to alterations of either mechanical function or electrophysiologic
properties of the heart, whereas chronic consumption can lead to progressive
cardiac dysfunction and congestive cardiomyopathy.
Alcohol in modest doses has
the potential of producing atrial or ventricular arrhythmias. Although many of
the pt have underlying heart disease, there are reports of pt with no evident
heart disease where acute alcohol ingestion has caused arrhythmias. This
sequence of events, (ie, cause and effect), has been referred to as the
"holiday heart" syndrome.
Pathologic effects of ethanol
on hematopoietic tissue can result directly from alcohol ingestion or from
secondary nutritional deficiencies or hepatic disease. The clinician will often
confront an array of overlapping syndromes in the alcoholic pt which involve
abnormalities of erythrocytes, leukocytes, and platelets.
The acute and chronic effects
of ethanol on pancreatic structure and function are discussed. Acute necrotizing,
acute edematous, acute relapsing, chronic relapsing, and painless pancreatitis
have an established association with ethanol abuse.
A case control study involving
interviews with the next of kin or close friends of 120 black males who recently
died of esophageal cancer and 250 similarly aged black males who died of other
causes was undertaken to discover reasons for the exceptionally high mortality
from this cancer in Washington, DC. The major factor responsible for the excess
was alcoholic beverage consumption, with an estimated 81% of the esophageal
cancers attributed to its use; high use of alcoholic beverages was also found
among the controls. The relative risk (RR) of esophageal cancer assoc with use
of alcoholic beverages was 6.4 (95% confidence interval= 2.5, 16.4). The RR incr
with amt of ethanol consumed and was highest among drinkers of hard liquor,
although the risk was also elevated among consumers of wine and/or beer only.
/Alcoholic beverages/
Intestinal permeability was
investigated with a (51)chromium-EDTA (edetic acid) absorption test in 36
non-intoxicated alcoholic pt without liver cirrhosis or overt clinical evidence
of malabsorption or malnutrition. Pt abstaining from alcohol for less than 4
days almost invariably had higher intestinal permeability than controls, and in
many the abnormality persisted for up to 2 wk after cessation of drinking. The
site of altered permeability was the small bowel. The incr intestinal
permeability to toxic "non-absorbable" cmpd of less than 5000 mol wt
may account for some of the extraintestinal tissue damage common in alcoholic
pt.
Although there is a dose
response relationship between alcohol consumption and liver damage, less than
one-third of alcoholics develop alcoholic liver disease (ALD). This individual
susceptibility to the development of alcoholic liver disease may be explained by
genetic and environmental factors. Of the genetic factors, female sex is clearly
a significant risk factor, HLA status is probably important but further studies
are needed, abnormalities in alcohol metabolism have not been shown to be of
primary pathogenic importance and the plethora of immunological disturbances
reported appear to be mere epiphenomena. Of the environmental factors, no
consistent evidence attests to the significance of hepatitis B viral infection
in the susceptibility to developing alcoholic liver disease.
Mortality from alcohol
poisoning was studied by age, sex, marital status and occupation in Finland in
1978-1982. Of 1204 fatal alcohol poisonings, 76 were due to methanol,
isopropanol, ethylene glycol, or combinations of these, the rest being due to
ethanol. Males predominated: the percentage of females was 11%. Mortality was
highest among persons aged 45-54 years. The risk of fatal poisoning differed by
marital status and was inversely related to socio-economic level. Thus, among
males aged 30-59 years, the age adjusted risk of death among divorced pensioners
was 15 times that of married men in upper stratum occupations. If all males were
at risk equal to that for married upper stratum men, the annual number of fatal
alcohol poisonings among males would decrease by 67%.
Eighteen asymptomatic post
menopausal women volunteered to ingest 2 ml of 100 proof vodka per kg of body
weight in orange juice on one night and a placebo on another. Overnight sleep
monitoring was performed immediately thereafter. Alcohol ingestion caused
reduction in total sleep time from 329 to 281 min and a decrease in rapid eye
movement sleep. There was no difference from placebo in the number of episodes
of apnea or hypopnea, or in the frequency, length, or severity of oxygen
desaturation. In contrast to the effects of alcohol ingestion in men, the
effects on breathing and oxygenation are minimal during the sleep of women, if
this amount of alcohol is ingested.
... ALCOHOL WITHDRAWAL IN PT
WITH SEVERE PHYSICAL DEPENDENCE ... THREE SOMEWHAT DISTINCT WITHDRAWAL STATES
THE TREMULOUS SYNDROME, ALCOHOL RELATED SEIZURE DISORDERS, AND DELIRIUM TREMORS
... MUCH OVERLAPPING ... TREMULOUSNESS, WHICH APPEARS WITHIN A FEW HOURS AFTER
THE LAST DRINK, IS OFTEN ACCOMPANIED BY NAUSEA, WEAKNESS, ANXIETY, AND SWEATING.
PURPOSIVE BEHAVIOR DIRECTED TOWARD OBTAINING ALCOHOL OR A SUITABLE SUBSTITUTE IS
PROMINENT. THERE MAY BE CRAMPS & VOMITING. HYPERREFLEXIA IS PROMINENT.
TREMORS MAY BE MILD OR SO MARKED THAT PT MAY BE UNABLE TO LIFT A GLASS. SUBJECT
MAY BEGIN TO "SEE THINGS," AT FIRST ONLY WHEN THE EYES ARE CLOSED BUT
LATER EVEN WHILE THE EYES ARE OPEN. INSIGHT IS AT FIRST RETAINED, AND SUBJECT
REMAINS ORIENTED. ... TONIC-CLONIC SEIZURES CAN OCCUR, BUT THEY ARE LESS COMMON
IN ALCOHOL WITHDRAWAL THAN IN BARBITURATE WITHDRAWAL. THE SPONTANEOUS EEG SHOWS
MILD BUT DEFINITE DYSRHYTHMIAS ... TREMULOUS STATE REACHES PEAK INTENSITY WITHIN
24 TO 48 HR, & SEIZURES ARE MOST LIKELY TO OCCUR WITHIN FIRST 24 HR AFTER
CESSATION OF DRINKING. IF THE SYNDROME PROGRESSES FURTHER, INSIGHT IS LOST;
SUBJECT BECOMES WEAKER, MORE CONFUSED, DISORIENTED, AND AGITATED. ... AT THIS
STAGE, WHICH APPEARS AROUND THE THIRD DAY OF WITHDRAWAL, PICTURE IS THAT OF
TREMULOUS DELIRIUM ... HYPERTHERMIA IS COMMON, & EXHAUSTION AND
CARDIOVASCULAR COLLAPSE MAY OCCUR. ... IF PT DOES NOT DIE, RECOVERY USUALLY
OCCURS WITHIN 5 TO 7 DAYS, WITHOUT TREATMENT.
HEAVY DRINKER-HEAVY SMOKER HAS
ABOUT 15 TIMES THE RISK OF THE NONSMOKER, NONDRINKER /OF DYING OF CANCER OF THE
ORAL CAVITY/.
The effect of embryonic
exposure to maternal drugs during cardiogenesis has been widely studied and the
evidence suggests that maternal use of ethanol ... may increase the risk of
congenital heart disease.
The metabolic effects of
ethanol are due to a direct action of ethanol or its metabolites. Ethanol causes
hyperglycemia or hypoglycemia depending on whether glycogen stores are adequate,
inhibits protein synthesis and results in a fatty liver with elevations in serum
triglyceride levels. Increases in high density lipoprotein cholesterol after
ethanol ingestion may explain the lower risk of myocardial infarction and death
from coronary disease after moderate drinking. Increases in serum lactate,
resulting from the increased NADH/NAD+ ratio, and hyperurecemia, most likely the
result of an increase in the turnover of adenine nucleotides, are common
transient effects of ethanol ingestion. Causes of vitamin deficiencies in
alcoholism are decreased dietary intake, decreased intestinal absorption, and
alterations in vitamin metabolism. Ethanol decreases thiamine absorption and
decreases the enterohepatic circulation of folate. Acetaldehyde increases the
degradation of pyridoxal 5'-phosphate by displacing it from its binding protein
and making it susceptible to hydrolysis by membrane bound alkaline phosphatase.
Ethanol decreases hepatic vitamin A concn and its conversion to active retinal,
and modifies retinal metabolism of vitamin D.
Amt that causes severe
alcoholic intoxication (300 mg % /in blood/) does ... cause change in cerebral
blood flow, metab, & vascular resistance. ... Cerebral oxygen uptake is much
reduced.
... Cirrhosis of liver that
occurs in 8% of chronic alcoholics in contrast to 1% of abstainers &
temporate drinkers may be, @ least in part, due to malnutrition ... .
In an experimental human study
the effect of toluene and ethanol (alone or in combination) on psychophysiologic
functions was studied in 12 men (22-44 yr of age). Each subject served as his
own control. Ethanol was ingested at a dose equivalent to 15 mmol ethanol/kg
body weight. Maximum blood levels of ethanol varied between 12-25 mmol/ml with a
mean value of 16 mmol/ml (0.09%). Ethanol intake impaired performance on 2 of 4
tests and significantly increased heart rate during performance testing (2-6
beats/min, 0.05>p>0.01). No interaction between ethanol and toluene was
observed.
MODERATE AMT OF ALCOHOL IN MAN
MAY STIMULATE OR DEPRESS RESPIRATION; VENTILATORY RESPONSE TO CARBON DIOXIDE IS
... ALWAYS DEPRESSED. LARGE AMT ( ... BLOOD CONCN OF 400 MG/DL OR MORE) PRODUCE
DANGEROUS OR LETHAL DEPRESSION OF RESP /USUALLY FATAL/.
An analysis of the baseline
data of the Paris Prospective Study 2 (3,348 middle-aged men) was done to assess
the independent associations between the fatty acids of cholesterol esters and
the main coronary heart disease risk factors. The association of alcohol
consumption, a strong correlate of some fatty acids, was also examined. The
alcohol consumption used in this study is a weighted sum of the different types
of alcoholic beverages consumed by a subject during a typical week and is
expressed in milliliters of alcohol per day. Palmitoleic acid was strongly
associated with alcohol consumption (an increase of one standard deviation of
the fatty acid with a mean increase of 15.6 ml/day alcohol consumption) and
blood pressure. /Alcoholic beverages/
Bone mineral density and
various biochemical and hormonal values were measured in 28 patients currently
drinking ethanol (drinkers), 12 patients claiming not to have consumed any
ethanol for at least 6 mo (abstainers), and 35 non-alcoholic control subjects
without clinical or biochemical evidence of liver disease. Iliac crest biopsies
were taken under local anesthesia in the patients and under general anesthesia
in the control subjects. Forearm bone mineral densities, spinal bone mineral
densities, and iliac crest cancellous bone areas were significantly lower in the
alcoholic patients compared with control subjects, but these values did not
differ between the drinkers and the abstainers. The drinkers had significantly
less osteoblastic activity than the abstainers, as assessed by dynamic bone
histomorphometry. No differences were seen relating to histologic parameters of
bone resorption, although the alcoholic patients who had lower serum free
testosterone concentrations than the control subjects also had higher urinary
hydroxyproline excretion rates.
The content of ethanol in the
blood, tissues, and body fluid was measured at autopsy of a 25 yr old female who
died from a suicidal overdose of imipramine, acetaminophen, codeine,
diphenhydramine, and ethanol. The quantity of alcohol imbibed was not known.
Blood samples were taken from at least 10 arterial and venous sites, and other
samples were taken from 24 tissues, cerebrospinal fluid, vitreous humor and
bile. Ethanol showed a narrow concentration range (151-175 mg/100 ml) in
postmortem blood.
The influence of alcohol
consumption and hepatic fibrosis on red blood cell membrane fatty acid
composition and susceptibility to lipid peroxidation were investigated.
Erythrocytes from chronic alcoholics with and without liver cirrhosis were
analyzed. Erythrocytes from alcoholics without liver cirrhosis contained an
increased proportion of saturated fatty acids over controls The cells contained
less linoleic acid than controls, but exhibited a normal degree of lipid
peroxidation upon oxidant stress induced by hydrogen peroxide. Erythrocytes from
alcoholics with liver cirrhosis contained less arachidonic acid than controls,
and were less susceptible to lipid peroxidation than controls.
A431 cells (ATTC), derived
from human epidermoid carcinoma of the vulva, were grown to 80% confluence,
using 4 ml of Dulbecco's minimum essential media supplemented with 1000 U/ml
penicillin, 100 ug/ml streptomycin and 10% fetal calf serum. Binding media
containing no ethanol, 25 mM ethanol or 100 mM ethanol were added to the
appropriate dish and each dish was incubated 20 min at 37 C. Each dish was then
brought to 1.6 nM epidermal growth factor and allowed to incubate at 37 C for 5
min. Three washes with ice cold Hank's plus 0.1% bovine serum albumin was
followed by 3 addnl washes with Hank's minus bovine serum alburium to remove any
remaining calf serum. The 1 N sodium hydroxide soln was counted in a gamma
counter. Lowry protein detns were done and statistics were calculated using the
Student's t-test. For each concn of ethanol tested, the rate of binding was 13
ng of epidermal growth factor/mg protein; showing that ethanol did not alter the
ability of A431 cells to bind epidermal growth factor to its membrane receptor.
/Alcoholic beverages/
Twelve human social drinkers
participated in a practice session plus four exptl sessions, each under a
different ethanol dose and given in counterbalanced order. The task entailed
forewarned, aimed transitive movements of the hand and arm, and entailed lifting
a stylus from a central resting point and moving it to the left or right to
contact a flanking target strip. A warning signal (light and tone) preceded the
response signal by a period of 4 sec. Separate measures of reaction time (ie,
time to lift stylus from central point) and MT (ie, subsequent time before
contact with flanking strip) were obtained, as were measures of decision
accuracy (ie, direction of response) and movement precision (ie, proportion of
responses making contact with the target strip). In one condition
(stimulus/response compatible), the correct response direction corresponded with
stimulus location, whereas in a second condition (stimulus/response
incompatible) the direction was opposite. Ethanol doses were 0 (placebo), 0.45
(low), 0.80 (medium) and 1.05 (high) g/kg lean body wt, mixed in a constant
volume with orange juice and consumed over a half hr period. Additional
maintenance doses of 0.12 g/kg were given at subsequent half hr intervals.
Ethanol and stimulus/response compatibility both affected RT, but there was no
suggestion of an interaction between the two variables. RTs were lengthened 31
msec by stimulus/response incompatibility, whereas at the highest dose, ethanol
increased reaction time by about 30 msec. Simultaneously recorded
movement-related brain potential disclosed decreased involvement of frontal and
posterior brain areas.
The effect of alcohol
(ethanol) abuse on muscarinic, cholinergic, and benzodiazepine receptors were
studied in the hippocampus of histologically normal human brains obtained at
autopsy in a general hospital population. Muscarinic, cholinergic synaptic
receptor density determined with tritiated quinuclidinyl benzilate was decr by
30% in homogenates of the hippocampus of 25 alcohol abusers compared with 25
matched nonalcoholic controls. Densities of benzodiazepine receptors determined
with (3)H flunitrazepam were also decr by approximately 30% in alcohol abusers.
The affinities of both receptor types were not affected by alcohol abuse. Age
and death to autopsy time interval had no significant effects on either wet
tissue protein concentrations, yields of protein after centrifugation, or
receptor binding. The contributions of age and time interval were each <2% of
the total variance of protein concn and receptor binding. When patients were
excluded or incl who had received cholinergic, anticholinergic, or
benzodiazepine medications before death, no significant effects on the final
results were observed. Pneumonia (associated with acute hypoxia) and chronic
obstructive pulmonary disease (associated with chronic hypoxia) were
approximately equally distributed between the two groups and had no significant
effects on the results.
Three polygraphic recordings
of afternoon sleep related to the duration of one sleep cycle (90 min) were
performed in 14 healthy adult volunteers (7 men and 7 women). Two reference
polygraphic recordings were made on two consecutive days (before ingestion of
alcohol) and only the second of these was retained. The third polygraphic
recording was taken on day 3, 50 min after the start of a single slow oral
ingestion of the equivalent of 0.25 g 95% ethanol/kg body wt. Alcohol was
ingested as 40 proof whiskey, and the vol administered ranged from 34.5 to 66
ml. Analysis of polygraphic traces was carried out according to the criteria of
Rechtschaffen and Kales, and results were presented using the parameters adopted
by Gross et al. A single low dose of alcohol leading to a low mean blood alcohol
level (<30 mg/100 ml, range to 29 mg/100 ml), perturbed sleep in the normal
nonalcohol dependent adult. The total duration of sleep, the percentage of delta
sleep, and the duration (and percentage) of rapid eye movement sleep were decr.
The number, duration, percentages of intrasleep awakenings, and the number of
stage changes were incr.
The relationship of alcohol
(ethanol) use to diet was examined in 2272 male and 2337 female adults aged 45
yr and older who provided a quantitative diet history during 1977-1979. Mean
values for each dietary variable, adjusted for smoking, ethnicity, income, and
education, were compared in each sex between abstainers and drinkers and by
tertile of ethanol intake. Linear relationships with extent of drinking were
also sought. Drinkers were found to be less obese than abstainers. Consumption
of carbohydrate, vitamins, calcium, fruits, fruit juices, and raw vegetables was
greater among abstainers whereas consumption of fat (particularly
polyunsaturated fatty acids), cholesterol, zinc, meat, pickled vegetables, and
dried fish was greater among drinkers.
Two hundred and seventeen
visitors to a county show (age 16 to 73) were taught to use the unit system for
estimates of alcohol (ethanol) consumption. All were tested on it until they
successfully answered three simple questions about its use. Altogether 150 had
heard of units of alcohol before, and 63 had counted their drinks in units. One
hundred and four subjects were asked to examine the usual retail containers for
3 wines, 3 lagers, and 3 beers. The wines contained 0.05%, 7%, and 13% alcohol
by vol; the lagers contained 0.9%, 3.4%, and 8.6%; and the beers contained 1%,
3.5%, and 10.9%. With one exception this was stated on the container, the strong
lager being labeled only with its original gravity (1076 to 1082). Each subject
was asked to estimate the number of units in one 150 ml glass of each wine and
in one pint (0.57 l) of each lager and beer. The remaining 113 subjects
underwent an identical procedure with larger amount of alcohol; the results were
comparable. Sample glasses were used to illustrate the amounts in both cases. In
the group of 104 subjects, between 80 and 88 correctly estimated the number of
units in the standard strength drinks. Fewer correctly estimate the strength of
the low alcohol drinks. Fewer still correctly estimated the strength of the
extra strong drinks: mostly this was greatly underestimated, with 53
underestimating the strength of the wine, 103 the lager, and 93 the beer. After
being told of the relative strengths of the drinks, 198 subjects agreed that it
would be a good idea for bottles and cans of alcoholic drink to display their
alcohol content in units.
A pretested questionnaire was
admin to 205 middle aged and elderly acute ischemic stroke patients and 410
outpatient controls matched by age, sex, race, and method of hospital payment.
The frequency of hypertension (p < 0.001), transient ischemic attacks (p=
0.051) mean weekly alcohol consumption (p= 0.0286), and mean pack yr cigarette
exposure (p= 0.0168) were higher among stroke index cases than controls. Mean
weekly alcohol consumption was 173.47 g among stroke cases, and 119.92 g for
controls. For weekly alcohol consumption, there was a highly significant dose
response effect. 60.2% of stroke cases and 75.8% of controls consumed 0
ethanol/wk. 10.0% and 6.4% consumed 1 to 99 g; 14.9% and 9.6% consumed 100-299
g; and 14.9% and 8.1% consumed > 300 g, respectively. Analyses to assess the
possibility of mutual confounding effects of independent variables, found
hypertension and smoking to be independent risk factors for ischemic stroke,
while alcohol consumption was not. Separate analyses by sex yielded similar
results.
The relationship of oral
cancer risk to types of alcoholic beverage consumed was investigated using data
from a hospital based case control study (1976 to 1983) on 511 male and 226
female cancer cases, and 1057 male and 453 female controls. Drinkers were
classified oral as consumers of predominantly beer, wine, or hard liquor (ie
more than 50% of their whiskey equivalents of alcohol derived from a specific
beverage). The number of predominantly wine drinkers was too small to permit
analysis. Logistic regression was used to obtain estimates of oral cancer
associate with each predominant beverage, with adjustment for other risk factors
and confounding variables, including smoking, age, yr of education, and
religion. In males, the odds ratio for predominantly beer drinkers increased
with incr level of intake, reaching 4.87 (95% confidence interval: 2.51 to 9.46)
in drinkers of 7+ oz of whiskey equivalents/day. The odds ratio for
predominantly hard liquor drinkers showed a similar incr, reaching 5.74 (95%
confidence interval: 2.94 to 11.22) in predominantly hard liquor drinkers
consuming 7+ oz of whiskey equivalents/day. In females, all 3 levels of drinkers
(1 to 3.9 oz/day, 4 to 6.9 oz/day and 7+ oz/day) had significantly elevated odds
ratios, but there was no clear gradient.
A case control study
comprising 216 cases of pancreatic cancer and 279 controls was conducted to
investigate the relationship of pancreatic cancer with the consumption of
alcoholic beverages. Cases and controls were stratified by sex and 10 yr age
groups in the analysis. Cases drank significantly more beer than controls (p=
0.005). The relative risk associated with recent regular consumption of more
than 7 pints of beer/wk, compared to nondrinkers, was 3.17 with a 95% confidence
interval (1.16, 8.64). Regular consumption of 7 pints/wk in the past was
associated with an estimated relative risk of 2.33, 95% confidence interval
(0.92, 5.96). No significant difference was found between cases and controls in
consumption of either wine or spirits and no differences between the sexes were
observed. Smoking was a clear risk factor, but cases and controls were very
similar with respect to tea and coffee drinking habits. The relative risks by
the amount of alcohol consumed has a significant positive trend with past
consumption (chi square= 3.88, df= 1, p= 0.05), but for recent consumption, the
evidence was not significant (chi square= 3.00, df= 1, p= 0.08). The effect of
alcohol appeared to be largely confined to the smokers, where the change in the
relative risk (measured on a logarithmic scale) was 0.02 per unit of alcohol (p=
0.03). No significant trend with amount of alcohol consumed was found in non
smokers.
The association between
alcohol consumption and risk of benign proliferative epithelial disorders (BPED)
of the breast was examined in a case control study conducted in Australia. The
study involved 383 cases with biopsy confirmed benign proliferative epithelial
disorders, 192 controls whose biopsy did not show epithelial proliferation, and
383 unbiopsied community controls individually matched (1:1) to cases on age and
area of residence. When cases were compared with community controls, the
unadjusted relative risk of benign proliferative epithelial disorders for
drinkers versus nondrinkers was 0.9 (95% CI= 0.6-1.3), and the corresponding
relative risk derived from comparing cases with biopsy controls was 1.0 (95% CI
=0.6 - 1.4). These estimates did not change after adjustment for potential
confounding. Variation in risk of benign proliferative epithelial disorders
across levels defined in terms of daily total alcohol intake, and in terms of
daily alcohol intake from individual beverages, was mostly insubstantial and not
dose dependent. With community controls as the comparison group, risks for women
who drank less than 1/4 of a glass, between 1/4 and 1 glass, and more than 1
glass of alcohol per day were 0.9 (95% CI= 0.6 - 1.3), 1.0 (95% CI= 0.7 - 1.5),
and 0.7 (95% CI= 0.5 - 1.1) respectively, compared to a risk of unity for
nondrinkers. Corresponding relative risks for cases versus biopsy controls were
0.8 (95% CI= 0.5-1.3), 0.9 (95% CI= 0.6-1.5), and 1.0 (95% CI= 0.6-1.7). Also,
there was little variation in risk with age at first drink, or by current
drinking status, and risk of benign proliferative epithelial disorders in
association with alcohol consumption did not incr with severity of cytologic
atypia.
The validity of self reported
daily alcohol consumption was established by correlating concentration of
ethanol in daily urine samples with number of reported standard alcoholic
drinks. The relationship was linear between 4 and 10 reported drinks. Ethanol
was detected in concentrations of less than 1.0 millimolar in 105 of the 287
urine samples from nondrinking days and at higher concentrations in 31 samples.
Only 53% of the samples from reported days of abstinence were negative for
ethanol. Only 94 of the 287 abstinent days were preceded by an abstinent day,
and no ethanol was detected in the urine from 65% of those days, small
quantities (0.05 to 0.999 millimolar) were detected in 31% of those days, higher
concentrations were detected in only 4%. In addition to inaccurate reporting,
other factors affected the correlation: the time between consumption of the
reported drinks and urine sampling and the time span over which the drinks were
consumed. By sampling 50% or fewer of the 84 days of a study for each subject,
values of the correlation coefficients or the rank positions of subjects did not
significantly change, but the 95% confidence intervals for the correlation
coefficients did increase.
Four female subjects (21 to 39
years) were asked to discriminate between a stationary light signal and one that
changed position in the center of a dark visual field before and during alcohol
administration. These tests were designed to evaluate two processes involved in
visual movement discrimination: visual sensitivity and decision making. Testing
was conducted on a total of 15 days during a 5 week period. The dose of alcohol
was 0.66 ml or 95% USP ethanol per kg body weight. Blood alcohol levels were
determined 12 times during each session. Average peak blood alcohol levels
ranged from 0.065% to 0.105%. The mean minutes to peak ranged from 20.5 + or -
9.3 to 50.3 + or - 8.6. Differences in performance of subjects before and after
alcohol consumption were evaluated within the framework of a psychophysical
model that characterized the problem of movement discrimination, producing
independent estimates of visual sensitivity and decisional aspects of
performance. Each subject made large and statistically reliable shifts in
decisional criteria during the alcohol testing sessions even when visual
sensitivity had adapted to alcohol intake effects.
Thirty eight subjects in the
Colorado Alcohol Research on Twins and Adoptees study were retested between 3
and 39 months after their initial testing. Subjects were given a dose of ethanol
(0.8 g/kg) calculated to bring their blood alcohol level to near 100 mg/dl, but
no topping doses were given in the retests to maintain blood alcohol levels near
peak for 3 hours as was done in the first test. Repeatability (test to retest
correlation) was near zero for alcohol clearance rate, 0.36 for time to peak
blood alcohol level, and 0.50 for peak blood alcohol level. Repeatabilities of
prealcohol baseline scores were 0.55 (median) for the shortened battery of
physiological, motor coordination, perceptual speed and reaction time measures.
Repeatabilities were near zero for sensitivity scores and low (median, 0.02) for
acute tolerance scores and perceived intoxication (median 0.27).
Topographic maps of brain
electrical activity from scalp EEG electrodes were obtained from health adult
female volunteers using a brain electrical activity mapping system. Each women
received both ethanol (0.7 g/kg oral) and placebo in a counterbalanced order
under double blind conditions at an interval of 1 to 6 days. Subjective reports
of intoxication were obtained continuously via an instrumental joystick device.
Subjects reported when they detected ethanol and qualitatively pleasant or
unpleasant effects. All subjects reliably discriminated ethanol from placebo.
Pronounced increases in EEG alpha activity occurred during ethanol induced
intoxication in all subjects. The distribution of the high amplitude, fast
frequency EEG alpha activity extended further frontally to the central sulcus
and temporally during ethanol intoxication than during control sessions or after
placebo administration. One woman with a positive family history of alcoholism
experienced only a mild degree of intoxication. This behavioral response was
accompanied by a slight decrease or no change in both slow and fast frequency
alpha activity.
2002 randomly selected
pregnant Australian women were recruited over a 3 yr period for a questionnaire
survey covering demographic, lifestyle, health, dietary, and obstetric factors.
58% of the women were in their first trimester, 33% in their 2nd trimester, 8%
in their third trimester at recruitment. Only 19 refused participation. When a
stratified subsample of 665 women were followed, there were 42 miscarriages, 72
stillbirths, and 6 neonatal deaths. The subsample, selected on the basis of
prepregnancy alcohol consumption, was followed through pregnancy. Data were
collected on obstetric course and infant outcome. Results showed that beer,
wine, and spirits drinkers differed significantly in maternal characteristics,
nutrition, and other important variables such as smoking. Women who miscarried
drank significantly higher volumes of beer (absolute ethanol intake from beer= 7
ml per day) than those with live births (3 ml) or stillbirths (3 ml). Beer
drinkers were less likely to reduce their consumption in pregnancy than other
drinkers if they also smoked more than 20 cigarettes per day.
Peripheral blood lymphocytes
from 12 alcoholic patients in good nutritional status and without heavy liver
damage and 15 healthy controls were used for studying the effects of chronic
ethanol on lymphocyte membrane alpha 1-glycoprotein and immune response to
various stimulating agents, including phytohemagglutinin, Ca ionophore A23187,
and autologous non-T-cells in (autologous mixed lymphocyte reaction). Compared
to controls, a significant impairment in AMLR was observed, but no difference
was seen in the response to the other stimulating agents. While the percentage
of alpha 1-glycoprotein bearing T-lymphocytes was significantly lower in
alcoholics (14.4 + or - 8.6) than in controls (31.9 + or - 8.1; no differences
were present in lymphocytes expressing other membrane glycoproteins, including
CD5, CD4, and CD8.
Data from the Luebeck Blood
Pressure Study, a cross-sectional study on a random sample (n = 3,100) of the 30
to 69 yr old population of Luebeck, were analyzed with regard to alcohol
consumption and blood pressure. Men who consumed >40 g/day alcohol had 5-6 mm
Hg higher mean systolic and 4-5 mm Hg higher mean diastolic blood pressure than
nondrinkers; there was a J-shaped relationship between alcohol consumption and
systolic blood pressure. About 7% of hypertension among the men was due to
alcohol consumption of >40 g/day. Among women, there was a strong interaction
between age and alcohol consumption. For women <45 yr old, the alcohol blood
pressure relationship was not pronounced. But for women >45, a strong
interaction between alcohol consumption and smoking was found. Compared to
female nonsmokers, there were steep increases in the adjusted mean diastolic
(5.2 mm Hg) and systolic (9.6 mm Hg) blood pressure of female smokers who
consumed >20 g/day alcohol.
ETHANOL & CERTAIN SHORT
CHAIN ARYL (BENZYL) & ALIPHATIC (PROPYL, BUTYL) ALCOHOLS PRODUCED UP TO 10
FOLD INCR IN CYCLIC AMP CONCN IN PURIFIED HUMAN PERIPHERAL BLOOD LYMPHOCYTES.
ETHANOL CONCN AS LOW AS 80 MG/DL PRODUCED SIGNIFICANT ELEVATIONS IN LYMPHOCYTE
CYCLIC AMP.
Symptomatology (acute
intoxication): 1. Early emotional lability: exhilaration, boastfulness,
talkativeness, remorse, and belligerency. 2. Impaired motor coordination: slowed
reaction time, slurred speech, ataxia. 3. Sensory disturbances: diplopia,
vertigo. 4. Flushing of face, rapid pulse, sweating. 5. Nausea and vomiting.
Eventual incontinence of urine and feces. 6. Drowsiness, stupor and finally
coma, with impaired or absent tendon reflexes. Convulsive episodes may indicate
hypoglycemia. 7. Pupils dilated or normal. 8. Peripheral vascular collapse
(shock): hypotension, tachycardia, cold pale skin, hypothermia. 9. Slow
stertorous respirations. 10. Death from respiratory or circulatory failure or
from aspiration pneumonitis. 11. During convalescence: postalcoholic headache
and gastritis; infections (for example, pneumonia, septicemia); alcoholic
psychoses (for example, delirium tremens).
Acute alcohol admin has been
shown to modify the ERG in ... human beings.
Fetal alcohol syndrome is the
name given to a collection of characteristic malformations that have been found
in the infants and children of mothers who drank alcohol during pregnancy.
Series of cases of eye abnormalities have been reported. ... Most common has
been horizontal shortness of the palpebral fissure due principally to an
abnormally large distance between the medial canthi. Also common are ptosis and
strabismus, either convergent or divergent. High myopia, amblyopia, and pale
optic discs have also been reported. These ocular abnormalities typically have
been associated with facial anomalies, subnormal wt, delayed growth, and mental
retardation.
In ... human males ... acute
exposure to alcohol primarily affects testicular synthesis and secretion of
testosterone. ... Ethanol and acetaldehyde inhibit enzymes involved in gonadal
testerone synthesis. ... Levels of estrogenic steroids incr as a result of
altered hepatic metabolism and clearance of androgens. Women ... do not appear
to be as sensitive to the direct gonadal effects of alcohol and may be less
vulnerable to antifertility effects with chronic alcohol abuse.
Seven pt undergoing long term
hemodialysis became addicted to vapor of denatured alcohol. Withdrawal symptoms
occurred in 2 pt who tried unsuccessfully to stop the practice. ... The handling
of motor vehicles was impaired by 100 mg/100 ml of alcohol in the blood, stupor
might result from 300 mg/100 ml, and resp failure and sometimes death from 400
mg or more per 100 ml. The fatal dose was about 1 l of 50% vol/vol spirit
ingested over a short period. In conjunction with other drugs, low concn of
alcohol might provoke significant toxic effects.
Analysis of 76 pt under 40 yr
of age with ischemic infarction, indicated that alcohol intoxication incr the
risk of brain infarction 2 to 3 times for men and 3 to 4 times for women. ...
Alcohol caused brain damage which might be common. ... Intellectual impairment
may be the earliest sign of alcohol abuse. A significant rise in blood-glucose
concn and a significant delay in insulin secretion were observed in 12 healthy
subjects 1 hr after drinking 50 ml of alcohol. ... Data from 83947 mem and women
of various races indicated that regular intake of 3 or more alcoholic drinks
daily was associated with raised blood pressure. ... Cancer of the mouth,
pharynx, and esophygus, and primary cancer of the liver appeared to be
definitely related to heavy consumption of alcohol in USA ... .
Blood alcohol concn (% wt/vol):
0.03-0.12; stage of alcohol influence/intoxication in nontolerant individuals:
euphoria; clinical sign/symptom: mild euphoria, sociability, talkativeness, incr
self-confidence, decr inhibitions, diminution of attention, judgment, and
control, loss of efficiency in fine performance tests /From table/
Blood alcohol concn (% wt/vol):
0.09-0.25 stage of alcohol influence/intoxication in nontolerant individuals:
excitement; clinical sign/symptom: emotional instability, decr inhibitions, loss
of critical judgment, impairment of memory and comprehension, decr sensory
response, incr reaction time, some muscular incoordination /From table/
Blood alcohol concn (% wt/vol):
0.18-0.30; stage of alcohol influence/intoxication in nontolerant individuals:
confusion; clinical sign/symptom: disorientation, mental confusion, dizziness,
exaggerated emotional states (fear, anger, grief), disturbance of sensation (diplopia)
and of perception of color, form, motion, dimensions, decr pain sense, impaired
balance, muscular incoordination, staggering gait, slurred speech /From table/
Blood alcohol concn (% wt/vol):
0.27-0.40; stage of alcohol influence/intoxication in nontolerant individuals:
stupor; clinical sign/symptom: apathy, general inertia, approaching paralysis,
markedly decr response to stimuli, markedly muscular incoordination, inability
to stand or walk, vomiting, incontinence of urine and feces, impaired
consciousness, sleep or stupor /From table/
Blood alcohol concn (% wt/vol):
0.35-0.50; stage of alcohol influence/intoxication in nontolerant individuals:
coma; clinical sign/symptom: complete unconsciousness, coma, anesthesia,
depressed or abolished reflexes, subnormal temp, incontinence of urine and
feces, embarrassment of circulation & respiration, possible death /From
table/
Blood alcohol concn (% wt/vol):
0.45+; stage of alcohol influence/intoxication in nontolerant individuals:
death; clinical sign/symptom: death from resp paralysis /From table/
Low doses result in behavioral
disinhibition. As the dose incr, sexual response is impaired, resulting in
failure of erection in males and reduced vaginal vasodilation and delayed orgasm
in females. Chronic use has been associated with an 8% rate of impotence,
one-half of which was irreversible despite abstinence from alcohol. The chronic
effects are probably the result of both neurological and endocrine effects;
alcohol has been shown to reduce testosterone levels and incr luteinizing
hormone levels. The chronic effects are independent of liver disease.
CUTANEOUS REACTIONS TO ETHANOL
WAS EVALUATED IN A CONTROL GROUP & IN PATIENTS BEFORE & WHILE THEY WERE
RECEIVING DISULFIRAM THERAPY. LOCAL CUTANEOUS ERYTHEMA WAS OBSERVED FROM PATCH
TESTS WITH ETHANOL IN HYDRATED SKIN. SINCE REACTIONS NOTED FROM TOPICALLY
APPLIED ALCOHOLS BEFORE & WHILE THE PATIENTS WERE RECEIVING DISULFIRAM
THERAPY WERE NOT STATISTICALLY DIFFERENT, A LOCALIZED DISULFIRAM-ALCOHOL
REACTION IS UNLIKELY. ERYTHEMA RESULTING FROM TOPICALLY APPLIED ALCOHOLS
OCCURRED IN A DOSE RELATED MANNER & WAS CAUSED BY A DIRECT VASODILATORY
EFFECT ON THE CUTANEOUS MICROVASCULATURE.
THE ACTIVITY Y PURIFIED HUMAN
ERYTHROCYTE ACID PHOSPHATASE (EAPASE) WAS ENHANCED 2.6 FOLD BY ETHANOL. THE
EXTENT OF HUMAN PROSTATIC ACID PHOSPHATASE (PAPASE) ACTIVATION BY ETHANOL WAS
LOWER THAN THAT OF EAPASE. EAPASE & PAPASE ACTIVATION BY ALIPHATIC ALCOHOLS,
INCLUDING ETHANOL, WAS NONCOMPETITIVE.
Results of 2 case control
studies of breast cancer which included questions on exposure to alcohol are
reported. One study included 998 hospital cases (married women, ages 25-59 yr)
and a like number of matched hospital controls while the other included 118
cases (women, ages 45-69 yr) diagnosed during mammographic screening and a like
number of matched normal screenees. Compared to the relative risk of 1.0 in
controls, the relative risks of breast cancer with alcohol consumption were 0.7
to 1.2, which were independent of the levels of alcohol consumed.
The relationship between
dietary habits and prognostic factors for breast cancer was studied in 240 women
(ages 50-65 yr) who had surgery for breast cancer between 1983 and 1986. A
dietary history interview was conducted within the 4 mo following resection of
the primary tumor. Bivariate analyses showed that the proportion of patients
with estrogen receptor rich tumors increased significantly with age (p <
0.05). These patients reported higher absolute values for intake of fiber and
retinol equivalents and lower absolute values for intake of alcohol. Estrogen
receptor rich tumors were more common in patients in the lowest quartile for E%
(percentage of total energy intake) from alcohol.
Exfoliated cells were
collected from the cheek and tongue of 27 men aged 35 to 69 yr. DNA was
extracted from the cells and analyzed by the enhanced (32)P-postlabeling
technique using butanol extraction. A variety of adduct spots were detected but
none was consistently associated with exposure to alcohol (ethanol). Some of the
adducts detected had migration patterns in thin layer chromatography very
similar to the major deoxyguanosine adducts formed by the diol epoxides of
benzo(a)pyrene and 5-methylchrysene. Adduct spots with migration patterns
similar to polynuclear hydrocarbon adducts accounted for only about one third of
the total adduct spots observed. Relative adduct labeling values were determined
for samples from 12 of the 27 men. Relative adduct labeling values ranged from
1.6X10-6 to 7.7X10-11 adducts/nucleotide. The relative adduct labeling values
for adducts from the cheek or tongue were not significantly different. Adduct
levels in drinkers (median relative adduct labeling of 9.1X10-10, n= 17) were
significantly lower (p < 0.001) than adduct levels in non-drinkers (median
relative adduct labeling of 3.7X10-8, n= 43). 4 of the subjects in this study
have subsequently developed squamous cell carcinoma of the oral cavity. 3 of 4
consumed at least the equivalent of one ounce of hard liquor per day.
(32)P-Postlabeling analysis of DNA from the oral cavity of these subjects did
not demonstrate unique patterns or relative adduct labeling values.
In study 1, 92 subjects (12 to
42 yr old) with fetal alcohol syndrome (n = 58) or fetal alcohol effects (n =
34) were admin an IQ test, a test of academic achievement, a test of auditory
receptive ability, and a test of adaptive and maladaptive behavior. Not all test
data were available on all pt. Over a 10 yr period, the IQ scores of pt with
fetal alcohol syndrome remained quite stable. IQ scores of adolescents and
adults with fetal alcohol syndrome or fetal alcohol effects were 70 + or - 17).
Pt with fetal alcohol syndrome had a significantly lower IQ than those with
fetal alcohol effects (mean IQ of 65 vs 80). With a median age of 15 yr, the 70
pt tested for academic achievement were functioning at the 3rd to 4th grade
levels for word recognition, spelling and arithmetic. 58% of the adults and
adolescents were classified as having significant levels of maladaptive
behavior. In study 2, 500 children were selected for participation in the study
based on maternal reports of alcohol use during pregnancy or prior to pregnancy
recognition. All children whose mothers were heavier ethanol drinkers were
selected, along with a proportion of moderate, light, and infrequent drinkers
and nondrinkers. Outcome (dependent) variables were assessed on days 1 and 2, at
8 and 18 mo, and at 4 and 7 yr of age. Follow-up of the cohort was 86% overall.
Prenatal alcohol exposure was related to significantly lower IQ scores even
though the mean IQ for the cohort was well within the normal range. When 6 to 8
yr olds were tested, both arithmetic and reading deficits were significantly
associated with prenatal alcohol exposure, even though the mean scores were
within the normal range for the age and grade of the subjects. On days 1 and 2
of life, significant neurobehavioral effects of prenatal alcohol exposure was
seen. At 8 mo of age, prenatal alcohol exposure was associated with small
decrements in mental and motor development. Neurobehavioral effects were also
seen at 4 and 7 yr of age.
Women in an antenatal clinic
were screened for alcoholism. Women who were positive, and an equal number of
non-alcoholic women matched on race, smoking, parity, date of recruitment, drug
abuse, prepregnancy wt, and wk gestation at registration formed the study group.
1284 offspring were examined for fetal alcohol syndrome linked anomalies and 359
mother-infant pairs were recruited into a prospective child development cohort.
At 4 yr, 10 mo, 239 mother-child pairs remained in the study. A tally of
neonatal anomalies was used as a marker for fetal alcohol effects. Three
different indicators of alcohol consumption (in-pregnancy, retrospective and
estimated embryonic) were used to evaluate effects of the avg oz of alcohol per
day (AA/day) consumed. Using the in pregnancy average oz alcohol per day data,
the heaviest drinking group (> 0.5 oz alcohol/day) differed significantly
from the abstaining group and from the low average oz alcohol per day groups
(between 0 and 0.1 oz/day) in total fetal anomalies. Five yr later, using the
retrospective index, no effect of ethanol on total fetal anomalies was seen for
the abstention group and the low average oz alcohol per day groups. Notable and
significant incr in total and craniofacial anomalies tallies were obtained at
the 2 highest drinking levels (from 0.5 to > 1.5 oz alcohol/day). With the
estimated embryonic average oz alcohol per day index, as well as the other 2, a
clear breakpoint, or threshold was seen in comparisons of heavy drinking groups
with low average oz alcohol per day groups (2.0 oz/day in the embryonic period).
A study of 400 infants born to
members of a health maintenance organization were investigated to study the
relation of the mother's use of alcohol (ethanol) during breast-feeding to the
infant's development at 1-yr of age. Mental development, as measured by the
Bayley Mental Development Index (MDI), was unrelated to maternal drinking during
breast-feeding. However, motor development, as measured by the Psychomotor
Development Index (PDI), was significantly lower in infants exposed regularly to
alcohol in breast milk (after alcohol exposure during gestation was controlled
for) with a dose-response relation (p for linear trend, 0.006). The infants of
breast-feeding mothers who had at least one drink daily had a mean Psychomotor
Development Index score of 98, whereas the infants exposed to less alcohol in
breast milk had a mean Psychomotor Development Index score of 103 (95%
confidence interval for the difference of the two means, 1.2 to 9.8). The effect
was more pronounced when mothers who supplemented breast-feeding with formula
were excluded from the analysis.
A cohort of 650 women was
interviewed at each trimester of pregnancy about their level of alcohol
(ethanol) intake. The mothers were classified as heavy alcohol users if they had
an avg of > or = 1 drink/day, moderate users for an avg of 3 to 6 drinks/wk,
and light users for an avg of < 2.9 drinks/wk. Data were reported for 595
live single births available for the followup study. A relationship was
demonstrated between prenatal maternal alcohol use and growth and morphologic
abnormalities in the offspring. Low birth wt, decr head circumference and
length, and an incr rate of fetal alcohol effects were all found to be
significantly correlated with exposure to alcohol during the first 2 mo of the
first trimester.
Plasma luteinizing hormone,
follicle stimulating hormone, prolactin, estradiol and progesterone were
measured in 24 normal, adult women before and after iv admin of 100 ug
luteinizing hormone releasing hormone (Factrel) and per os ingestion of an
alcohol (0.694 g ethanol/kg body wt) or placebo soln. 12 subjects were studied
during the early follicular phase of the menstrual cycle and 12 subjects were
studied during the midluteal phase of the menstrual cycle. During each menstrual
cycle phase, 6 subjects received placebo soln and 6 subjects received alcohol
soln admin under double blind conditions. Mean peak blood alcohol levels of 113
to 122 mg/dl were measured 45 to 60 min after initiation of alcohol intake.
During the follicular and the luteal phases of the menstrual cycle there were no
significant differences in luteinizing hormone releasing hormone-stimulated
follicle stimulating hormone or the prolactin response between the alcohol and
placebo conditions. During the midluteal phase of the menstrual cycle, estradiol
increments were also significantly higher after luteinizing hormone-releasing
hormone and alcohol than after luteinizing hormone releasing hormone and placebo
alcohol intake, but progesterone levels did not change. Acute alcohol
intoxication induced a significant incr in plasma estradiol levels after
luteinizing hormone releasing hormone admin during the follicular phase of the
menstrual cycle and augmented the estradiol response to luteinizing
hormone-releasing hormone stimulation during the luteal phase of the menstrual
cycle.
ETHANOL & CERTAIN SHORT
CHAIN ARYL (BENZYL) & ALIPHATIC (PROPYL, BUTYL) ALCOHOLS PRODUCED UP TO 10
FOLD INCR IN CYCLIC AMP CONCN IN PURIFIED HUMAN PERIPHERAL BLOOD LYMPHOCYTES.
ETHANOL CONCN AS LOW AS 80 MG/DL PRODUCED SIGNIFICANT ELEVATIONS IN LYMPHOCYTE
CYCLIC AMP.
Most epidemiologic studies of
the relationship between alcohol consumption and breast cancer risk over the
past decade have shown that persons who consume a moderate amount of alcohol are
at 40-100% greater risk of breast cancer than those who do not consume alcohol.
Dose-response effects have been observed, but no causal relationship has been
established. This study examined the hypothesis that alcohol consumption affects
levels of reproductive hormones. A controlled diet study lasting for six
consecutive menstrual cycles was conducted. Participants were randomly assigned
to two groups, and a crossover design was used. During the last thee menstrual
cycles, alcohol consumption of the two groups was reversed. Thirty-four
premenopausal women, aged 21-40 yr, with a history of regular menstrual cycles,
consumed 30 g of ethanol (equivalent to approximately two avg drinks) per day
for three menstrual cycles and no alcohol for the other three. All food and
alcohol consumed were provided by the study. Caloric intake was monitored to
ensure that each woman would maintain body weight at approximately the baseline
level. Hormone assays were performed on pooled plasma or 24 hr urine specimens
collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and
mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each
diet. Alcohol consumption was associated with statistically significant
increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate
levels were 7.0% higher in the follicular phase (p= .05). In the peri-ovulatory
phase, there were increases of 21.2% (p= .01) in plasma estrone levels, 27.5%
(p= .01) in plasma estradiol levels, and 31.9% (p= .009) in urinary estradiol
levels. In the luteal phase, urinary estrone levels rose 15.2% (p= .05),
estradiol levels incr 21.6% (p= .02), and estriol levels rose 29.1% (p= .03). No
changes were found in the percent of bioavailable estradiol, defined by the sum
of percent free estradiol and percent albumin-bound estradiol. However, incr
total estradiol levels in the peri-ovulatory phase suggest elevated absolute
amounts of bioavailable estradiol. This study has shown incr in total estrogen
levels and the amount of bioavailable estrogens in association with alcohol
consumption in premenopausal women. ...
Drug Warnings:
BRIEFLY APPLIED TO THE SKIN,
70% ALCOHOL DOES NO DAMAGE, BUT IT IS IRRITATING IF LEFT ON FOR LONG PERIODS OF
TIME. AS THE RESULT OF REMOVAL OF CUTANEOUS LIPIDS, FREQUENT USE CAUSES DRY SKIN
AND SCALINESS. IRRITATION IS SOMETIMES CAUSED BY DENATURANTS IN ETHANOL. APPLIED
TO WOUNDS OR RAW SURFACES, ETHANOL NOT ONLY INCR INJURY BUT ALSO FORMS A
COAGULUM UNDER WHICH BACTERIA MAY SUBSEQUENTLY THRIVE. IT IS THUS NOT USED TO
DISINFECT OPEN WOUNDS.
Ethanol potentiates the
central nervous system effects of numerous sedative and depressant drugs. ... It
should not be used by patients taking certain prescription drugs ... .
Maternal Medication usually
Compatible with Breast-Feeding: alcohol (ethanol): Reported Sign or Symptom in
Infant or Effect on Lactation: With large amounts drowsiness, diaphoresis, deep
sleep, weakness, decrease in linear growth, abnormal weight gain; maternal
ingestion of 1 g/kg daily decreases milk ejection reflex. /from Table 6/
Medical Surveillance:
Look for chronic irritation of
mucous membranes and signs of chronic alcoholism in regular physical exam. Ethyl
alcohol can readily be determined in blood, urine, and expired air.
The determination of ethanol
in blood, breath or urine sampled during or just after the work period can
provide a useful index to exposure. ... The blood alcohol concn should not
exceed 200-300 mg/l in exposed workers. Pre-exposure specimens should be taken
to rule out nonoccupational sources of ethanol.
Employees should be screened
for history of certain medical conditions ... /skin, liver, kidney, eye, or
chronic respiratory diseases central and peripheral nervous systems/ which might
place the employee at increased risk from butyl alcohol exposure. ... Any
employee developing the ... conditions should be referred for further medical
exam.
Probable Routes of Human Exposure:
Humans will be exposed to
ethanol by ingestion of foods, flavorings, beverages, and pharmaceuticals (SRC).
Workers will be exposed to ethanol in occupational settings associated with its
manufacture, use as a solvent or use in synthesis(1), or when released as a
product of fermentation, decomposition or combustion (including cigarette
smoke)(2).
Inhalation of vapor and
percutaneous absorption ... eye and skin contact.
NIOSH (NOHS Survey 1972-1974)
has statistically estimated that 3,240,470 workers are exposed to ethanol in the
USA(1). Finnish furniture factory, 1975-84, 394 samples, 70% pos, 32 ppm avg of
pos(2).
There is probably greater
exposure to ethanol than to any other solvent with the exception of water. Not
only is it used as a solvent in industry, but it is heavily consumed by large
numbers of people as a component of potentially intoxicating beverages. As a
result of the petroleum shortage, plans call for diluting gasoline with ethanol
to form a combustible product termed "gasohol". At that point it is
likely that ... /there will be/ universal exposure to ethanol.
Animal Toxicity Studies:
Evidence for Carcinogenicity:
A4; Not classifiable as a
human carcinogen.
Non-Human Toxicity Excerpts:
ANIMALS EXPOSED TO ETHYL
ALCOHOL IN AIR MAY MANIFEST THE FOLLOWING SIGNS OF INTOXICATION: SLIGHT
IRRITATION OF THE MUCOUS MEMBRANES, EXCITATION FOLLOWED BY ATAXIA, DROWSINESS,
PROSTRATION ... /CNS DEPRESSION/, TWITCHING, GENERAL PARALYSIS, DYSPNEA, AND
OCCASIONALLY DEATH ASSOCIATED WITH RESPIRATORY FAILURE.
IN LAB ANIMALS ...
ANTICONVULSANT ACTION IS FOLLOWED BY PERIOD OF HYPEREXCITABILITY THAT LASTS FROM
12 HR (AFTER SINGLE DOSE) TO SEVERAL DAYS (AFTER CESSATION OF CHRONIC ADMIN).
DIRECT DEPRESSION OF HEART BY
ALCOHOL HAS BEEN OBSERVED FOLLOWING ITS ACUTE ADMIN TO EXPERIMENTAL ANIMALS;
BOTH MYOCARDIAL CONTRACTILITY AND WORKING EFFICIENCY MAY BE ADVERSELY AFFECTED
BY A BLOOD CONCN AS LOW AS 100 MG/DL. ELECTRON MICROSCOPIC OBSERVATIONS REVEAL
CHARACTERISTIC INTRACELLULAR LESIONS IN THE MYOCARDIUM, ASSOC WITH CONGESTIVE
HEART FAILURE; PROGNOSIS FOR RETURN OF MUSCLE FUNCTION IS GUARDED.
CHRONIC ETHANOL INGESTION IN
MALE RATS INCR CYTOCHROME P450 CONTENT & ACTIVITY OF MICROSOMAL
BENZO(A)PYRENE HYDROXYLASE IN THE UPPER INTESTINAL MUCOSA. INTESTINAL MICROSOMES
FROM ETHANOL FED RATS ALSO EXHIBITED ENHANCED CAPACITY TO ACTIVATE
BENZO(A)PYRENE TO A MUTAGEN.
ADMIN OF ETHANOL (500 ML/DAY
IN FEED) TO PREGNANT DOGS FOR 20 WK FROM 1ST DAY OF PREGNANCY INDUCED SLIGHT,
BUT MORPHOL AND BIOCHEM DISCERNABLE, CHANGES IN THE CNS OF THE PUPS. THESE
CHANGES INCL NEURONAL DAMAGE WITHIN THE FRONTAL & HIPPOCAMPAL CORTEX &
PURKINJE CELL LAYER, & DECR IN LEVEL OF CHOLESTEROL ESTERS AS COMPARED TO
CONTROL PUPS.
FEMALE RATS WERE PAIR-FED
USING ISOCALORIC CONTROL OR 6.6% (VOL/VOL) ETHANOL LIQ DIETS FOR 1 MO PRIOR TO
CONCEPTION & THROUGHOUT GESTATION. ETHANOL PUPS SHOWED PREMATURE ONSET &
SLOW-DOWN OF ACTIVE MYELINATION.
24-HR LC50 VALUE FOR RAINBOW
TROUT IN FLOW-THROUGH BIOASSAY SYSTEM @ 10 DEG C WAS 11200 MG/L. ETHANOL AT
ABOUT O.26 OF THE FINGERLING LC50, AFFECTED CARDIOVASCULAR/RESP SYSTEMS IN
ADULTS. SLIGHT VENTILATION RATE & BUCCAL PRESSURE AMPLITUDE DEPRESSION
OCCURRED IN INITIAL STAGES OF 24 HR EXPOSURE. Q-T INTERVAL DECREASED.
Treatment of CD-1 mice with 7
g/kg ethanol ip on one of gestational days 7, 8, 9, 10, or 11 significantly incr
the percentage of malformed fetuses and decr fetal wt.
Ethanol ... is capable of
breaking the physiological gastric mucosal barrier and may cause ultrastructural
injury to the epithelial cells within several minutes of exposure. Ethanol at
any pH, ... is lipid soluble and diffuses rapidly into surface epithelial cells.
... First, the nuclear chromatin becomes clumped and the density of the
cytoplasmic ground substance decreases, followed by the mitochondria becoming
swollen and the apical cell membrane distorted. Finally, the apical cell
membrane ruptures and the cell disintegrates. Throughout this sequence, the
tight junctions between cells appear morphologically intact.
The direct effects of ethanol
on cardiac contractility are controversial, probably because of methodological
reasons in relation to the choice of appropriate experimental models. The direct
effects of 1, 2, 5 and 10 g/l ethanol on mycardial performance and metabolism in
the isolated perfused working guinea pig heart was studied. In the normal heart
ethanol induced a dose dependent, fully reversible depression of cardiac
contractility without significant changes of heart rate or cardiac metabolism.
In the post anoxic failing heart this effect was more pronounced. Ethanol had no
arrhythmogenic effect even at high concentrations. It had no measurable effect
on anoxic induced alterations or post anoxic recovery after a period of 20 min
of anoxic perfusion. Anoxic induced lactate production was decreased in hearts
pretreated with 10 g/l ethanol. The direct negative inotropic effect and the
lack of chronotropic effect of ethanol was studied. They suggest the lack of
effect on excitability. The mechanism of the negative inotropic effect does not
seem to be metabolically related since cardiac O2 consumption and lactate
production remain unaltered.
Ethanol (0.6 g/100 g) was
administered orally to rats by means of an intragastric tube. This caused an
accumulation of secretory vesicles laden with very low density lipoprotein (VLDL)
particles which were seen 90 min after administration and later disappeared.
Lysosomes and Golgi complex secretory vesicle (GCSV) fractions were isolated.
The proteolytic and lipolytic activities of these fractions were measured in
order to assess their possible role in the elimination of the initially retained
secretory material. There was no change in proteolysis either in lysosomes or in
the GCSV-fraction from ethanol-intoxicated rats when measured by the release of
degradation products during incubation. Similarly, the activities of acid
hydrolases were unaffected by acute ethanol intoxication. On the other hand,
lipolysis increased by some 50-100% in the GCSV fraction, whereas the lysosomes
displayed unchanged lipolytic levels compared with controls. Ultrastructurally,
the GCSV-fraction from ethanol-intoxicated rat livers showed signs of
disintegrated VLDL particles. It is concluded that acute ethanol intoxication
causes an increase in lipolysis but not in proteolysis in the operationally
defined GCSV fraction. Since triacylglycerol lipase activities did not change in
the GCSV fraction, increased amounts of substrate seem to cause the enhanced
lipolysis observed.
Luteinizing hormone (LH)
secretory patterns were characterized in adult male and female rats exposed to
ethanol during the last week of fetal life. Gonadectomized fetal alcohol exposed
(FAE) males and females had significantly reduced plasma LH titers as compared
with those of pair fed (PF) controls. The phasic afternoon LH secretory response
to estrogen and progesterone priming was also significantly reduced in FAE
females. These differences do not appear to be a result of altered pituitary
sensitivity to luteinizing hormone releasing hormone (LHRH), since the infusion
of LHRH resulted in an equal response in PF and FAE females. Subsequent
characterization of the episodic pattern of LH secretion in FAE males revealed
significantly reduced mean LH level, as well as, a decreased pulse amplitude and
frequency when compared to PF males. Taken together, these data indicate that
some of the central mechanisms controlling pituitary LH secretion are altered by
prenatal exposure to alcohol.
In response to single ethanol
administration orally, the catecholamine secretion from the adrenal medulla is
enhanced as evaluated by urinary catecholamine excretion in rats. The threshold
dose of 87 mmol/kg also produced a transient increase of blood sugar concn.
Experiments with chronic ethanol treated rats showed that the increase of
urinary catecholamine excretion following 87 mmol/kg disappeared occasionally,
whereas the increase following repeated administration of 130 mmol/kg is
permanent. Morphologic evaluation revealed enlargement of the adrenal medulla,
changes of cells and nuclei as well as a distinct reduction of chromaffin
reaction.
Pregnant Wistar rats
(15/group) were exposed in inhalation chambers to 0, 10,000, or 16,000 ppm
ethanol for 7 hr/day on gestation days 1-20. Groups of male Wistar rats
(18/group) were exposed for 7 hr/day for six weeks. Exposed males were mated
individually with unexposed virgin females for 5 days after completion of
exposures. After parturition, pups from both maternally- and paternally-exposed
groups were fostered to untreated females. Neither female or male rats exposed
to 10,000 or 16,000 ppm ethanol showed any adverse effects. Offspring number
(average of 14 pups/litter) was not affected at either concentration of ethanol.
Behavioral testing revealed no differences from controls after maternal exposure
to ethanol.
Twelve pregnant Sprague-Dawley
rats were treated with a 12.5% v/v solution of ethanol in saline (0.015 ml/g
body weight) administered ip on gestational days 6 thru 12. Control animals (12
rats) received an ip injection of saline. A third group of 22 rats were used as
untreated controls. Embryos were removed on day 12 of gestation and studied. Of
the 150 alcohol treated embryos, four embryos showed a delay in the development
of cardiac primordia: instead of a differentiated heart, they had a beating
"S" shaped cardiac tube. A distorted head shape and central nervous
system defects were also present in some of the embryos. No alterations occurred
in either the yolk sac circulatory system or the allantois in embryos of this
group when compared to controls.
Pregnant Hartley guinea pigs
averaging 57 days of gestation (3rd trimester) were given four 1 g/kg body
weight doses of ethanol (ETH) administered orally at 1 hr intervals. Animals
were sacrificed between 0.5-26 hr after treatment and the pharmacokinetics of
ETH and acetaldehyde(AC) were determined. There was a bidirectional placental
transfer of ETH between maternal fetal compartments with a peak concentration in
blood and brain at 4.5 hr after administration and ETH accumulation in the
amniotic fluid. AC concentration was at least 1000 fold less than the respective
ETH concentration. Fetalethality was observed during the 9-26 interval after
administration of ETH (55% at 23 hr). At this time interval, the AC
concentration in maternal blood and fetal brain were 4 to 5 fold higher in the
animals with dead fetuses when compared with animals with live litters.
The effects of glutathione (GSH)
depletion on enhancing ethanol induced hepatotoxicity was investigated by
measuring the serum concentrations of glutamic-pyruvic-transaminase (GPT) and
sorbitol dehydrogenase (SDH) in rats. Male Wistar rats (7-8/group) were treated
with phorone (250 mg/kg in 10 ml/kg olive oil ip) to deplete hepatic GSH, and 2
hr later with ethanol (1.6 g/kg iv). Controls received olive oil instead of
phorone and saline instead of ethanol. In saline treated animals the GPT and SDH
concentrations remained nearly constant during the test period (up to 25 hr),
and no differences were seen between phorone pretreated rats and controls. In
the normal rats treated with ethanol, there was a small but statistically
significant increase in the GPT and SDH values 4 hr after treatment. However, in
the phorone pretreated rats that also received ethanol, there was a several-fold
statistically significant increase in both enzyme activities at 4 hr ; increases
in enzyme activities were also seen at 2 hr (SDH), 3 hr (both enzymes), and 25
hr (GPT) after treatment.
Blood ethanol concn and
reactive capacity of 10 young (8 months) and 5 old (24 months) male Fischer 344
rats were compared at 5, 10, 20, 45, 65, and 90 min following admin of ethanol (EtOH).
Time dependent effects of intragastric intubation (3 g/kg) and ip injection (1.5
g/kg) of EtOH (20% w/v) were determined. Subsequent of IG delivery, blood
ethanol concn rose most rapidly within the first 20 min, but did not reach peak
levels until 90 min for both young (240 mg/dl) and old rats (250 mg/dl).
Following ip injections, blood ethanol concn escalated within 5 min to 250 mg/dl
in the young, to 175 mg/dl in the old, and declined gradually to a stabilized
value of 150 mg/dl (young) and 130 mg/dl (old). The old rats never achieved the
high blood ethanol concn seen in the young. Reactive capacity, a measure of
auditory/visual reaction time, was inversely related to blood ethanol concn. As
blood ethanol concn (ip) declined, performance improved at a similar rate in
both age groups, although the old rats' performance was more impaired than that
of the young. However, when ethanol was delivered by IG so that blood ethanol
concn remained high for long periods of time, reactive capacity was far less
impaired compared with ip delivery in which comparable blood ethanol concn were
present for only a few minutes.
Twenty three 6-8 wk old male
and female mice of various strains (Swiss, Balb/c, DBA/2, CBA, C57B1/6, and
B6D2F1) received a topical application of a 95% solution of ethanol on both
sides of the right ear on days 0 and 2, and a scapular sc injection of 0.05 ml
of complete Freunds adjuvant on day 2. On day 9, left ear thickness was measured
immediately before topical application of 95% ethanol (the maximal nonirritating
concn), on both sides of the ear, and again 24 hr later (day 10). No
statistically significant incr in ear thickness was seen. In another test
procedure, anesthetized male (n=9) and female (n=10) Swiss mice received a sc
injection of 0.05 ml of ethanol in complete Freunds adjuvant into the scapular
region, together with a topical application of ethanol on the shaved abdomen. On
days 3, 5, 7, 10, 12, and 14 they received a topical application on the shaved
abdomen and a second scapular sc injection of 0.05 ml complete Freunds adjuvant
on day 7. On day 26, left ear thickness was measured immediately before a
topical application of ethanol on both sides of the ear. Left ear thickness was
again measured on days 27 (24 hr after challenge) and 28 (48 hr later). No
significant incr in ear thickness was seen.
Adult male Sprague Dawley rats
were implanted with indwelling gastric cannula one wk prior to expt.
Intragastric infusion of 4 g/kg ethanol into naive rats resulted in a rapid and
substantial incr of release the stress hormones adrenocorticotropic hormone,
corticosterone, epinephrine, and norepinephrine stress hormones. The mean SEM of
the percent incr over basal levels (at 100) for adrenocorticotropic hormone was
572, 329, and 391 for 7.5, 15, and 60 min after ethanol admin, respectively; and
for corticosterone values were 229, 202 and 368. For epinephrine, the incr after
15, 30, and 60 min was 550, 773, and 105, while that for norepinephrine was 229,
212, and 179, respectively. In another expt, rats were pretreated with either
ganglion blocker (pentolinium, 5 mg/kg body wt) 5 min before ethanol admin, or
were bilaterally adrenodemedullectomized two wk prior to the ethanol infusion.
Neither procedure, which effectively eliminated the ethanol induced surge of
catecholamines, resulted in a significant attenuation of the ethanol secretion
of adrenocorticotropic hormone or corticosterone.
The effect of ethanol (10, 25,
50, 100, 200, and 400 mM) on muscarine stimulated release of
(3)H-norepinephrine, (3)H-NE was studied using the rat pheochromocytoma cell
line, PC12. At concn of 25 mM and above, ethanol produced a dose dependent
inhibition of muscarine stimulated release of (3)H-NE (86.1-36.9% of control).
The inhibition of muscarine stimulated transmitter release occurred in the
absence of any effect of ethanol on (3)H-NE uptake, metabolism, or on muscarinic
binding to the cells. However, ethanol produced an inhibition of muscarine
stimulated elevation of intracellular free Ca(+2) which corresponded with the
inhibition of transmitter release. At concn greater than 100 mM, ethanol
produced both a stimulation of the release of (3)H-NE as well as an incr in
intracellular free Ca(+2)> At 100 mM ethanol the incr in free Ca(+2) was
73.2% of control, and at 400 mM it was 50.8%. Ethanol (400 mM) causes approx a
20% incr in the basal rate of (3)H-NE release, accompanied by an elevation of
the basal level of intracellular free Ca(+2) from 114 nM to 149 nM. The incr in
basal transmitter release and intracellular free Ca(+2) occurred independent of
the inhibition by ethanol of muscarine stimulated elevation in intracellular
free CA(+2) or transmitter secretion.
C57BL mice were fed ethanol in
a liquid diet for seven days and were withdrawn for various intervals. Chronic
ethanol ingestion, leading to functional tolerance and physical dependence,
significantly decreased the number of cerebellar antagonist binding sites, while
the affinity was not affected. In cerebellar membranes, the proportion of high-
and low-affinity ISO binding forms of BAR was not altered after chronic ethanol
ingestion. The affinity for ISO of the high affinity ISO binding form of the
receptor was significantly decreased.
Groups of NIH Swiss mice (n=
7) were admin 0, 10, or 20, mg/kg of one of three 5-hydroxytryptophan uptake
inhibitors (fluoxetine), citalopram, or (fluvoxamine) or a noradrenaline uptake
inhibitor (desipramine) ip 90 min prior to testing, followed by an ip injection
of either 0 or 2.4 g/kg ethanol in distilled water vehicle 30 min prior to
testing in the holeboard, followed by the elevated plusmaze test of anxiety.
Ethanol increased activity in both tests, decreased both the number and duration
of head dips in the holeboard, and increased both the percentage time and
percentage entries on to the open arm of the plusmaze. None of the inhibitors
significantly altered any of the behavioral measures. The only consistent
interaction was seen with fluoxetine which reduced ethanol's anxiolytic effects
at the 20 mg/kg dose without altering ethanol's effects on exploration or
locomotion.
The influence of alcohol
consumption and hepatic fibrosis on red blood cell membrane fatty acid
composition and susceptibility to lipid peroxidation were studied using male
Sprague Dawley rats. Cells from seven rats chronically treated with ethanol (20%
ethanol in tap water for 14 wk (11 g ethanol/kg body wt)) or from 15 rats
treated with thioacetamide (0.5 g/1 in tap water for 14 wk), an inducer of
hepatic fibrosis, were analyzed. Red cells from the ethanol treated rats had
minor changes in fatty acid composition compared with controls (n= 7). There was
a slight decrease in the proportion of arachidonic acid and a slightly decreased
susceptibility of the cells to lipid of peroxidation. Cells from rats with
hepatic fibrosis had an increased proportion of linoleic acid and a decreased
proportion of arachidonic acid compared to controls (n= 15). These cells were
less susceptible to lipid peroxidation.
The substitution of drinking
water in 26 male Wistar rats for a 10% ethanol solution for 4 wk in blood= 0.78
+ or - 0.13 mM/l resulted in a decr of blood urea and citrulline synthesis in
liver mitochondria; a slight inhibition in state 3 and state 4 respiration
either with glutamate malate as substrates or succinate as substrate; no change
in adversive diphosphate:oxygen ratio with succinate but slight incr with
glutamate malate; a reduction of the cytochrome oxidase activity and cytochromes
a + cytochrome a3 content; a 42% incr in the succinate dehydrogenase activity
and a small but constant incr in the Vmax (no change in the Km) of the adenine
nucleotide translocase activity in liver mitochondria.
The effect of ethanol (0.5
g/kg, iv) at different concn (30, 60, and 90%) was studied in male cats using
radioactive microspheres on systemic hemodynamics and regional circulation.
Ethanol produced a significant fall in systolic, diastolic and mean blood
pressure. A significant reduction in heart rate, left ventricular work, cardiac
output and total peripheral resistance was also observed. No change occurred in
stroke volume. A significant decr in blood flow to left ventricle, right
ventricle and interventricular septum was observed, but the vascular resistance
of these regions was unaltered. Brain blood flow was not affected by various
concn of ethanol. The vascular resistance significantly decr in spinal cord,
medulla, pons, midbrain, hypothalamus, thalamus, caudate nucleus, cerebellum and
cortex. The avg brain blood flow (ml/min/100 g) was 35.63 in control, 37.17 in
30%, 35.56 in 60% and 35.05 in 90% ethanol treated cats. Spleen, liver,
pancreas, gastrointestinal tract, skin, muscle and bone did not show any
significant change in the blood flow, while vascular resistance decr
significantly in these organs. Kidneys and eyes showed decr blood flow and no
change in vascular resistance following ethanol treatment. The blood passing
through the arteriovenous shunts was significantly decr by ethanol.
Subcutaneous injection of
neonatal gray opossums with 2 mg ethanol on day 2 and day 4 of life in the right
or left hindquarter resulted in defects of the associated limb in 44% of the
animals. The abnormalities, as recorded on day 21, were gait abnormalities, foot
clubbing, moderately reduced limb size, fuse digits, missing digits, and in one
case, a partially missing limb. Saline solution was administered to the control
group, of which 16% had defects such as gait abnormalities, foot clubbing, and
moderately reduced limb size. The opossums at birth were equivalent in
development to a human fetus at 8 weeks and therefore useful for studying
teratogenicity.
Ethanol (7.5 g/kg) was
administered to neonatal rats in four consecutive feedings spaced two hours
apart on either postnatal day 4, 5, or 6, via gastrostomy feeding tubes.
Controls consisted of rats suckled in the normal manner and gastrostomy group
fed formula. Ethanol exposures resulted in high peak blood alcohol concn (mean
peak blood alcohol concn of 380, 439, and 460 mg/dl on days 4, 5, and 6,
respectively). Whole brain weights as measured on the tenth postnatal day were
greatest in the naturally suckled animals, slightly less in the gastrostomy
controls, and significantly reduced in the ethanol fed rats. Ratios of whole
brain to body weight were 3.703 in the suckle control, 3.423 in the gastrostomy
control, 3.301 in day 4 ethanol group, 3.100 in day 5 ethanol group, and 3.102
in day 6 ethanol group. The cerebellum was affected more than the forebrain or
brain stem, and cerebellar growth was more stunted by alcohol exposure on day 4
or 5 than on day 6. Small but significant delays in body growth occurred 1 to 2
days after the alcohol exposure for each group.
Groups of female mice were
admin 5.8 g/kg (95% alcohol in saline intragastrically in a single intubation
(0.3 mg/10 g body wt) on day 10 plus 4 hr of pregnancy. This dose of ethanol
produced a blood ethanol concn of approx 450 mg % 60 min after injection.
Control group animals were intubated with saline made isocaloric to the ethanol
dose by addition of sucrose. On day 19 of gestation, fetal urogenital systems
were examined by injection of indigo carmine into the bladder. 53 control and
116 ethanol treated fetuses were examined. Ethanol resulted in a significant
decr in fetal wt. Malformed limbs, mostly in the form of fused digits (25 in
all) were also seen in the ethanol treated animals but not in the controls.
There was a significant increased incidence of hydronephrosis and hydroureter.
In addition, there was a significant incr in reflux in the ethanol treated
fetuses. The incidence of reflux appeared to be related to the severity of the
hydronephrosis observed, though cases of hydronephrosis without reflux and
reflux without hydronephrosis were found. Reflux occurred in only 7.1% of
ethanol treated mice with a mild degree of hydronephrosis but in 46.1% of the
mice with an extreme degree of hydronephrosis.
The effects of physical
addiction to ethanol, withdrawal from ethanol addiction, and the genetic
predisposition for drinking ethanol on the transport of enkephalins and
Tyr-MIF-1 (Tyr-Pro-Leu-Gly-amide) across the blood brain barrier were studied in
different strains of mice. In chronic oral ethanol exposure, 120 male ICR mice
were fed 5% ethanol by vol via the diet for 10 days and half of the group was
changed to sucrose mixture to constitute the withdrawal group. Male mice were
genetically selected for predisposition to ethanol using strains C57BL/6J,
C58/J, and DBA/2J (25 to 30 mice per strain). In acute ethanol exposure, mice
received either 0.9% sodium chloride or 2.5 g/kg of ethanol ip in a vol of about
0.2 ml (20% ethanol) and transport was determined 0, 10 30, 45, 60, 90, or 120
min later. In other mice, the effect of incl ethanol in the ICV injections at
concn of 0, 0.01, 0.05, 0.2, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 10, 15, 20
and 50% by vol was determined. During chronic exposure mice ingested an avg of
25 g/kg of ethanol/day. No statistically significant differences occurred among
control mice with inhibitor, ethanol treated mice, or ethanol treated mice with
inhibitor, indicating that ethanol primarily reduced the inhibitable portion of
transport. Brain weights were different for genetically predisposed mice, as
were half time disappearance rates and transport rates. Ethanol given in acute
ip doses did not produce any differences in values for A or M of the transport
equation or transport rate. In mice receiving ICV ethanol, values for A and the
transport rate were statistically different from 0% at the 50% concn.
The effect of cause associated
with gastric infusion of ethanol on the free choice consumption of ethanol by
male Sprague Dawley rats was assessed. Rats received a response independent
conditioning experience with a distinctive drinking environment. Group RM-EtOH
(n= 8) were given ethanol in a distinctive room and Group EtOH (n= 8) were given
ethanol in their home cage after they had been returned from the distinctive
room). Controls either received saline infusions either at the same time as
Group RM-EtOH in the distinctive room or as Group EtOH (n= 4) in the home cage.
On conditioning days 1 to 4, 2 g/kg ethanol was admin, and on days 5 to 10, 4
g/kg was admin. After training, rats were allowed daily free access to both an
ethanol soln and tap water. In Expt 1, infusion of 20% ethanol reduced ethanol
consumption on a choice test between 10% ethanol and tap water, compared with
saline. The highest level of consumption was in controls, then Rm-EtOH, then
EtOH. In Expt 2 the procedures were the same, except 2 g/kg ethanol was used, in
a more palatable soln (0.1% saccharin + 10% ethanol) and was compared with
consumption of tap water. Prior infusion with ethanol enhanced the consumption
of the sweetened ethanol only when drug associated cues were present (group
Rm-EtOH). In Expt 3, rats first received 10 24 hr periods of exposure to the
sweetened 10% ethanol soln in their home cages. By the fourth exposure, animals
had reached a stable level of consumption of about 40 ml of ethanol soln per
day. Procedures were the same as the previous 2 expt. Levels of ethanol
consumption were considerably higher than in Expt 1 and 2.
Two groups of 6 male Wistar
rats were pair matched on a wt basis and fed a liquid diet containing either 18%
of total calories as ethanol or pair fed isovolumetric amounts of the same diet
in which the ethanol was substituted by isocaloric glucose (controls). After 3
to 7 days, the proportion of ethanol calories was increased to 36% with
isocaloric incr of glucose in controls. Rats were sacrificed at 4 to 5 wk.
Chronic ethanol consumption reduced the capacity for type II (anaerobic, fast
twitch) fiber rich skeletal muscles to synthesize protein as reflected by a decr
RNA/protein ratio. Type I (aerobic, slow twitch) fiber rich muscles were
unaffected. A significant 12 to 190% reduction of skeletal muscle wt was seen,
but ethanol feeding had no significant effect on cardiac output. The percentage
of cardiac output to type I and type II fiber rich muscles, bone and tissue of
the gastrointestinal tract was unaffected by ethanol consumption. Similarly,
ethanol feeding had no effect on blood flow when it was calculated on the basis
of tissue wt (ml/min/g).
The effect of ethanol
(0.01-1%, v/v, or approx 1.74 to 174 mM) on single channel currents activated by
N-methyl-D-aspartate (NMDA) in cultured hippocampal cells from Sprague Dawley
rats were studied, using the outside out patch clamp technique. At low concn
(1.74 to 8.65 mM) an incr in the probability of opening (p sub open) of the NMDA
activated channel currents was seen without change in the mean channel open
time. At higher concn (86.5 to 174 mM), a decr in p sub open (to 50% of
controls) was seen with a concomitant decr in the mean open time.
Male Sprague Dawley rats
(160-80 g) were pair fed liquid diets containing 36% calories as ethanol or an
isocaloric mixture with maltose dextrin substituted for ethanol. Animals
received progressive incr in ethanol during the first wk of feeding and were
maintained on a reverse light dark cycle. Expt were started in overnight fasted
animals, and all studies were performed between 6 and 8 wk of feeding unless
otherwise noted. No incr of biliary hepatic glutathione (GSH) efflux in vivo was
found in chronic ethanol fed hepatocytes. Hepatocytes from pair fed and ethanol
fed rats were treated to obtain a wide range of cellular GSH concn. The
relationship between cytosolic GSH and the rate of efflux was modeled by the
Hill equation, revealing a similar sub max, 0.22 + or - 0.013 vs 0.20 + or -
0.014 nmol/min per 10+6 cells for ethanol fed and pair fed cells, respectively,
whereas the Km was significantly decr (25.3 + or - 2.3 vs 33.5 + or - 1.4 nmol/10+6
cells) in ethanol fed cells. The difference in Km was larger when the data were
corrected for the increased water content in ethanol fed cells. There was a
direct correlation between mitochondria and cytosolic GSH, revealing that
mitochondria from ethanol fed cells have less GSH at all cytosolic GSH values.
The rate of resynthesis in depleted ethanol fed cells in the presence of
methionine and serine was similar to control cells and gamma-glutamylcysteine
synthetase remained unaffected by chronic ethanol. Levels of cytosolic and
mitochondrial total GSH and the rate of GSH efflux were determined in pair fed
and ethanol fed cells from rats at 2 and wk of treatment. At 2 wk, a selective
50% decr in mitochondrial GSH was observed (p < 0.01), without an effect on
cytosolic total GSH or efflux. By 4 wk, the mitochondrial total GSH fell
further, while a fall in cytosolic total GSH and increased efflux were evident
in the ethanol fed group.
Cardiac membrane tissue from
left ventricles of male rabbits was used to characterize the effects of ethanol
on the activators of adenylate cyclase complex that act through the receptor
site, the stimulatory guanine nucleotide binding regulatory protein, or the
catalytic unit. Ethanol had no effect on adenylate cyclase activity stimulated
by Mn +2, a selective activator of the catalytic unit, whereas high
concentrations of ethanol (>425 mM) inhibited both basal and isoproterenol
stimulated adenylate cyclase. In contrast, in the presence of nonhydrolyzable
GTP analogs, ethanol potentiated substantial increases in adenylate cyclase
activity. In the presence of these GTP analogs, ethanol increased the Vmax
without altering the affinity of adenylate cyclase for ATP. Ethanol also
increased adenylate cyclase activity (4.5 fold) in membranes in which the
guanine nucleotide binding regulatory protein had been preactivated with
isoproterenol plus a nonhydrolyzable GTP analog. Beta adrenoreceptor density in
rabbit heart membranes was 9.8 + or - 2.1 fmol/mg membrane protein with ethanol
and 10.4 + or - 1.7 fmol/mg protein without ethanol. The ability of cholera
toxin and NAD+ to augment adenylate cyclase activity through an effect on
guanine nucleotide binding regulatory protein was attenuated by increasing
concentrations of ethanol.
A brief exposure of recently
ovulated mouse oocytes to a dilute solution (7%) of ethanol in vitro for 1, 3,
or 5 min induced a uniform high incidence of parthenogenetic activation. The
majority of parthenogenones developed a single haploid pronucleui after the
extrusion of a second polar body. The proportionate incidence of this
parthenogenetic class was significantly reduced as the duration of ethanol
exposure increased from 1 min to 5 min. There was a concomitant increase in the
incidence of parthenogenones that developed two haploid pronuclei following
failure of extrusion of the second polar body. The ethanol induced single
pronuclear haploid parthenogenones at metaphase of the first cleavage division
were aneuploid. The incidence of aneuploidy was directly related to the duration
of ethanol exposure (15.1% at 1 min, 15.5% at 3 min, and 25.7% at 5 min). G-band
analysis of the aneuploid metaphases revealed that the chromosomes were not
randomly involved in the malsegregation events.
Three female Macaque monkeys
were trained to self administer alcohol intravenously during four daily sessions
at noon, 4 PM, 8PM and midnight. Each session lasted 1 hour or until 20 alcohol
injections of (0.12 g/kg) had been administered. In one amenorrheic alcohol
dependent monkey, prolactin levels increased from 16.5 to 63 ng/ml during
chronic, high dose alcohol self administration (3.4 g/kg/day);
immunocytochemical examination of the anterior pituitary showed apparent
hyperplasia of the lactotrophs. Four amenorrheic cycles (85 to 194 days) from
two other alcohol female monkeys that self administered an average of 2.97 to
4.4 g/kg/day of alcohol were also studied. Each monkey became amenorrheic during
the first menstrual cycle that alcohol was available. One monkey developed
galactorrhea during a 97 day amenorrheic cycle when alcohol self administration
averaged 3.35 g/kg/day. Although prolactin levels were intermittently elevated
above 20 ng/ml, average levels during these amenorrheic cycles (14.7 + or - 1.8
to 19.6 + or - 1.5 ng/ml) did not differ significantly from prolactin levels
during normal ovulatory menstrual cycles when no alcohol was available (19.7 +
or - 0.36 ng/ml). Daily alcohol dose and prolactin levels were negatively
correlated. High dose alcohol self administration was often associated with low
normal prolactin levels, but a relative fall in alcohol dose was usually
associated with elevated prolactin levels. Luteinizing hormone levels were
significantly lower during amenorrheic cycles (16.9 + or - 1.2 to 24 + or - 1.4
ng/ml) than during nonalcohol control cycles (28 + or - 1.2 to 3 + or - 2.2 ng/ml).
The effects of ethanol and
sulfhydryls on gastric mucosa were studied by dosing male rats with 1 ml of 50%
ethanol by esophageal intubation. One hour after ethanol administration the
animals were sacrificed and the gastric wall prepared for examination.
Pretreatment with subcutaneous diethylmaleate (1 ml/kg), cysteamine (100 mg/kg)
and 16,16-dimethyl prostaglandin E2 (10 ug/kg) significantly inhibited lesion
formation. Pretreatment with N-ethylmaleimide (10 mg/kg) aggravated the lesions.
Ethanol did not change the action of the other chemicals on glutathione levels
in mucosa. N-Ethylmaleimide significantly enhanced the vascular permeability in
the presence or absence of ethanol whereas the other agents significantly
enhanced only the increased vascular permeability caused by ethanol. At doses
which prevented ethanol induced mucosal injury, diethylmaleate, cysteamine and
16,16-dimethyl prostaglandin E2 potently inhibited gastric motility, whereas N-ethylmaleimide
had no effect on motility.
The effects of ethanol in
thyroid disease were studied in three groups of female rats. Group I was given
L-thyroxine as subcutaneous pellets to induce hyperthyroidism, Group II was
given propylthiouracil as subcutaneous pellets to induce hypothyroidism, Group
III served as controls. Rats then received slow intravenous infusions of ethanol
until they lost their righting reflex. The hypnotic dose of ethanol was
increased significantly in the hyperthyroid rats (3.26 + or - 0.20 g/kg) and
decreased in hypothyroidism (2.32 + or - 0.31 g/kg) (control 2.82 + or - 0.15).
Ethanol concentrations in serum, brain, and cerebrospinal fluid at onset of
effects were generally not affected by thyroid dysfunction except for a small
increase of serum ethanol concentration in the hyperthyroid rats.
The effects of prenatal and
postnatal exposure to ethanol on luteinizing hormone releasing hormone and
luteinizing hormone were investigated in female rats and their offspring. Group
1 rats (control, no ethanol) were fed a liquid diet during gestation and
lactation. Group 2 rats were fed ethanol in a liquid diet during gestation and
the control diet during lactation. Group 3 rats were fed the control diet during
gestation and ethanol in a liquid diet during lactation. Group 4 rats were fed
the diet containing ethanol during both gestation and lactation. Female
offspring were decapitated at 30 to 40 days. Hypothalamic luteinizing hormone
releasing hormone contents in all the ethanol exposed groups (0.13 to 0.29 ng/hypothalamus)
were less than that of the controls (0.80 and 1.05 ng/hypothalamus). Plasma
luteinizing hormone concentrations of all ethanol exposed groups were less than
those of controls (24.2 and 29.6 ng/ml): 18.9 an 17.8 ng/ml in animals from
group 2 mothers (ethanol during gestation only), 5.7 and 6.8 ng/ml in animals
from group 3 mothers (ethanol during lactation only) and 10.7 and 8.5 ng/ml in
animals from group 4 mothers (ethanol during both gestation and lactation).
Blood glucose and rectal
temperatures were monitored in genetically obese mice (C57 BL/6J ob/ob) prior to
and following intragastric ethanol administration (12 mg/g body weight) in an
attempt to relate the hypothermic response to ethanol to extracellular glucose
concentration. Lean litter mates served as controls. Room temperature was
controlled at 21.5 + or - 0.2 C, and animals were placed on a neutral surface,
protected from drafts. In obese mice, ethanol administration was associated with
hyperglycemia and hypothermia; however, the hypothermia was independent of blood
glucose levels and of age.
Chinese hamster ovary cells
exposed to 4% ethanol did not acquire any apparent chromosomal aberrations.
However, posttreatment with ethanol potentiated the chromosomal aberrations
induced by ultraviolet light, methyl methanesulfonate, mitomycin C or bleomycin.
Chromatid exchanges were predominantly increased in cultures treated first with
the ultraviolet light, methyl methanesulfonate, or mitomycin C and then with
ethanol, whereas chromosome breaks and chromatid exchange were the major types
of aberrations increased in the cultures treated with bleomycin and ethanol.
Cerebellar granule cells from
excised cerebella of 8 day old Sprague Dawley rats were incubated with
N-methyl-D-aspartate (10, 50, or 100 uM) in the presence of (0, 25, 50, or 100
mM) ethanol. Measurements of calcium uptake and cyclic guanosine monophosphate
production demonstrated that ethanol preferentially inhibited N-methyl-D-aspartate
receptor gated cation channel function. Concn of ethanol as low as 10 mM
inhibited N-methyl-D-aspartate stimulated Ca(+2) uptake by > 30%. Ethanol
also inhibited N-methyl-D-aspartate stimulated (Ca(+2)) dependent) cyclic
guanosine monophosphate accumulation in a similar, dose dependent manner. The
IC50 values for ethanol were 42.7 mM at 10 uM, 74.4 mM at 50 uM, and 156.7 mM at
100 uM N-methyl-D-aspartate. With 100 uM kainate, 100 mM ethanol did not
significantly inhibit the cyclic guanosine monophosphate response: 16.0 + or -
9.4% inhibition (n= 4).
Groups of 6 adult male Sprague
Dawley rats were admin saline or ethanol in saline ip daily for 7 days and
killed 24 hr after the last dose. The doses of ethanol were 0.5, 1.0, and 3.0
ml/kg. Other groups of 6 rats were admin saline or ethanol (3 ml/kg ip) for 7
days. Carbon tetrachloride in corn oil (1.0 ml carbon tetrachloride/kg as a 50%
solution in corn oil, ip) was admin on day 8, and measurements of butanol
oxidase were made 24 hr later. 2-Butanol was incubated with microsomal lung and
liver preparations from rats, and methyl ethyl ketone production was measured by
gas chromatography. The rate was 6 to 8 times lower in lung than in liver. Admin
of the two low doses of ethanol did not alter activity in the liver but was
inhibitory in the lung. The high dose of 3.0 ml/kg caused a 41% inhibition in
the liver and a 51% inhibition in the lung. The effects of ethanol and carbon
tetrachloride were not additive.
Preimplantation two cell stage
mouse embryos, obtained from superovulated CF-1 mice, were exposed to ethanol
through the culture medium for 60 min followed by a 105 hr incubation period.
Scoring was based on a system which recognized eight different stages of
development, zero for dead cells of the two and four cell stage to 7 for
hatching blastocyst. Control and ethanol exposed embryos survived equally well
in ethanol concentrations as high as 800 ng/100 ml medium, the highest
concentration tested.
The apparent pharmacological
regulation of ethanol ingestion by rats was examined under the effects of wt
restriction and enhanced palatability, two variables that have been shown to
incr ethanol (alcohol) consumption when the alcohol is continuously available.
Incr the palatability of the ethanol solution by the addition of a 0.25%
saccharin solution enhanced consumption substantially such that the blood
alcohol levels achieved in male Wistar rats were more than twice those of rats
which had drunk unadulterated alcohol. Wt restriction to 80% of free feeding wt
of male Wistar rats did not incr alcohol consumption under these conditions.
The effects of ethanol on the
incidence and histology of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine
were investigated in Wistar rats. Rats received alternate-day ip injections of
2.5 ml/kg body wt of 20% ethanol in 0.9% sodium chloride solution after 20 wk of
oral treatment with N-methyl-N'-nitro-N-nitrosoguanidine. Prolonged
administration of ethanol resulted in a significant incr in the incidence and
number of gastric cancers of the glandular stomach in wk 52. However, it had no
influence on the histological types of the gastric cancers. Furthermore, it
caused a significant incr in the labelling index of the epithelial cells of the
antrum in wk 52.
Length changes in dendritic
networks of cerebellar Purkinje cells were studied in aging Fischer 344 rats
after chronic ethanol treatment. Results showed that no significant metric
changes in lengths of dendritic segments were detectable immediately following
24 wk of ethanol treatment. However, significant changes were observed after 8
wk of recovery from the ethanol treatment. The differences in lengths were
restricted to terminal segments that were paired at the peripheral tips of the
bifurcating networks. Unpaired terminal segments and internal segments did not
show significant changes during the recovery period.
Effects of prenatal alcohol
exposure during the last week of gestation on immune function and levels of
brain corticotropin releasing factor (CRF) and ACTH were studied in Sprague-Dawley
rats. Immune response was measured by T-lymphocyte proliferation in response to
the T-cell mitogen concanavalin A in spleen and thymus cells of 21 day old male
rats that had been exposed to alcohol in utero. The T-lymphocyte proliferative
response was 8 fold less in spleen and twofold less in thymus cells from fetal
alcohol exposed (FAE) animals as compared to controls. Thymus wt was
significantly lower at birth in fetal alcohol exposed males but significantly
higher at age 21 days, compared to controls. Both hypothalamic corticotropin
releasing factor and pituitary ACTH contents were significantly decreased in
fetal alcohol exposed males on postnatal day 1, but hypothalamic ACTH content
was significantly elevated compared to controls.
Neonatal Camborough piglets
were put under nitrous oxide anesthesia. In the first exptl series, piglets were
given either ethanol (1.4 g/kg) in 5% dextrose in water infusion over 50 min via
the femoral vein or an equal volume of vehicle only. In the second series, all
piglets also received a 15 min iv infusion of 50 mg/kg 4-methylpyrazole 15 min
before ethanol or vehicle infusion. Two hours after ethanol admin, blood
pressure decr from 76 + or - 4 to 71 + or - 4 mm Hg and heart rate increased
from 194 + or - 10 to 227 + or - 8 beats/min. By 5 hr, blood pressure dropped to
67.5 + or - 4 mm Hg and heart rate increased to 239 + or - 8 beats/min. In
piglets pretreated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor,
there was a transient incr in blood pressure and a decr in heart rate
immediately after the end of the ethanol infusion. However, the hemodynamic
alterations observed 2 hr after ethanol treatment alone were prevented with
4-methylpyrazole. The mean ethanol metabolic rate derived from plasma data was
94 + or - 9 mg/l/hr.
The influence of ethanol on
the activities of 3-hydroxy-3-methylglutaryl CoA reductase (HMG-CoA-reductase)
and squalene-hopene-cyclase (SC) in hopanoid biosynthesis of Zymomonas mobilis
subsp mobilis (ATCC 29191). By use of (14)C and (3)H-labelled substrates, the
enzymes were detected with activities of 1.6 pmol/(min x mg protein)
HMG-CoA-reductase and 2.3 pmol/(min x mg protein) for squalene-hopene-cyclase.
Cells grown in the presence of 6% (v/v) ethanol did not show higher activities
of these enzymes than cells grown in the presence of 1% (v/v) ethanol. Alcohol
dependent induction of HMG-CoA-reductase in Z mobilis was examined by
cultivation of cells at different ethanol concn and measurement of the
corresponding enzyme activity. Cells grown in batch or continuous cultures at
47-74 g/l ethanol showed an even lower HMG-CoA-reductase activity than cells
grown with 20 g/l glucose (producing ethanol concn < 1% v/v) without
externally added ethanol. Squalene-hopene-cyclase activity was the same in crude
extracts of Z mobilis cells grown in 2.5% or 8.5% ethanol. A significant incr of
enzyme activity was caused by addition of ethanol to the assay. An ethanol concn
of 60 g/l (7.6 v/v) led to enzyme activities of up to 5.8 pmol/(min x mg
protein).
A CORRELATION BETWEEN HYPNOTIC
POTENCY OF ALIPHATIC ALC & ABILITIES TO DISRUPT STRUCTURE OF NEURONAL
MEMBRANE IN VITRO WAS ESTABLISHED. SIGNIFICANT REDN IN ORDER PARAMETER WERE
OBSERVED @ NERVE BLOCKING CONCN. THE FOLLOWING ALCOHOLS WERE INVESTIGATED:
ETHANOL, PROPANOL, 2-PROPANOL, BUTANOL, 2-BUTANOL, 2-METHYL-1-PROPANOL,
2-METHYL-2-PROPANOL. DISORDERING POTENCY OF EACH ALCOHOL WAS CLOSELY RELATED TO
ITS MEMBRANE SOLUBILITY, BASED ON OIL/WATER PARTITION COEFFICIENT.
RATS WHICH INGESTED A 2 MOLAR
SOLN OF ETHANOL FOR 2 MO SHOWED MALLORY'S ALCOHOLIC HYALINE BODIES IN THE LIVER
& ALSO DECR IN FAT, GLYCOGEN, & RNA OF THE LIVER.
IN THE RAT ... THE ORDER OF
INCREASING LETHALITY BY SINGLE DOSE ORAL ADMIN IS AS FOLLOWS: ETHYL, ISOPROPYL
AND SEC-BUTYL, N-BUTYL, TERT-BUTYL, ISOBUTYL, & AMYL ALCOHOLS.
... About 50% inhibition of
ammonia oxidation in Nitrosomonas at 4100 mg/l
Guinea pig: inhalation: no
signs of intoxication: 6400 ppm, 8 hr; 3000 ppm, 64X4 hr; Rat: inhalation: no
signs of intoxication: 10,750 ppm, 0.5 hr; 3260 ppm, 6 hr
A drop full-strength on rabbit
eyes causes reversible injury graded only 3 on a scale of 10 after 24 hr.
Application of 70% alcohol to rabbit corneas injures and temporarily loosens the
corneal epithelium, but the recovery is complete. ... repeated applications (7
drops) of 40 to 80% alcohol to rabbit eyes over an unspecified but presumably
longer time caused loss of corneal epithelium and endothelium, followed by
hemorrhages in the conjunctiva, and infiltration and vascularizarion of the
corneal stroma.
Acute alcohol admin has been
shown to modify the ERG in rabbits, monkeys ... .
... The equivalent of 0.3 ml
of ethanol /was injected/ into the chick air sac at 23 hr of incubation and
produced neural tube and cerebral vesicle deformities along with some mesodermal
defects. ... /1.0 to 2.0 g of ethanol per kg was injected to/ pregnant rats iv
at 6 and 7 days of gestation ... and ... embryolethality but no defects in the
surviving fetuses /were found/. ... Pregnant mice /were fed/ before and during
pregnancy with a ... diet containing 15 to 30% ethanol derived calories. At the
higher concn resorptions occurred frequently. Neural defects and cardiac
malformations were found in a significant number of offspring. ... incr
susceptibility to audiogenic seizures /was found/ in offspring of mice given
alcohol. Learning is impaired in rats exposed during intrauterine life.
... The effects of binge
drinking /were studied/ in three monkeys. ... 2.5 or 4.1 g/kg /was given/ by
gavage once weekly from 40 days gestation to term. One nd facial exposed to the
highest dose had neurologic, developmental a anomalies. ... One of the other two
exposed to the lower dose had similar but less severe findings.
Porcine pulmonary artery
endothelial cells were cultured on micropore filters and the effect of ethanol
on albumin transfer across cultured endothelial monolayers was studied. Chronic
ethanol exposure resulted in a marked increase in albumin transfer compared with
control cultures, and this difference in albumin transfer increased with
increasing cell age. In contrast to its effects on endothelial barrier function,
chronic ethanol exposure had little effect on endothelial cell growth
characteristics. Even though thymidine incorporation into cell DNA was
significantly less at passage 50 in ethanol treated cells compared with control
cultures, the overall DNA and protein synthesis rate and the cell total DNA and
protein content were not markedly affected by chronic ethanol exposure.
24 adult mongrel dogs were fed
a diet (5 days per wk) mixed with 3 g/kg ethanol (ETOH) for 3 mo (group 1, n =
12) and 9 mo (group 2, n = 12); 12 dogs were fed a regular diet with no alcohol.
Blood alcohol levels 2 to 3 hr after food consumption were 116 + or - 10 mg/100
ml. On the experimental day, both ETOH treated and ETOH free dogs were divided
into two subgroups, one for hemorrhagic shock (mean arterial pressure of 30 mm
Hg for 2 hr) and one for observation during anesthesia. Chronic ethanolism
altered cardiocirculatory function (increased mean arterial pressure (p <
0.05), arterial lactate, and hematocrit (p < 0.05) and decr cardiac output (p
< 0.05), stroke work, and pancreatic blood flow (p < 0.05)) regardless of
the length of time ETOH was consumed. Hemorrhagic shock impaired cardiovascular
performance regardless of ETOH consumption. However, coronary blood flow,
myocardial oxygen delivery, extraction, and consumption were significantly
higher (p < 0.05) in the ETOH treated compared with ETOH free dogs after 2 hr
of shock. Cardiocirculatory dysfunction after fluid resuscitation from shock in
the ETOH group was not related to inadequate coronary perfusion, metabolic
acidosis, or cardiac hypertrophy. Examination of myocardial tissue by light
microscopy showed no significant difference in myocyte size in any group
regardless of chronic ethanol consumption. Hypercontraction lesions occurred in
all shocked hearts, both intoxicated and nonintoxicated. There were not
myocardial lesions in any nonhemorrhaged dog. There was increased total
myocardial tissue calcium content in the ETOH group.
Young male Wistar rats (80 to
100 g body weight) were fed a nutritionally adequate liquid diet containing
ethanol as 36% of total energy. Controls were fed the same diet in which ethanol
was substituted by isoenergetic glucose. At the end of 6 wk, rats were killed
and hearts were fractionated into sarcoplasmic, myofibrillar and stromal protein
fractions by differential solubilization. The total myofibrillar protein content
was significantly (p < 0.01) reduced by chronic ethanol feeding, though the
contents of other fractions were relatively unaltered. The fractional and
absolute rates of myofibrillar protein synthesis were significantly increased (p
< 0.05), but the synthesis rates of sarcoplasmic and stromal protein
fractions were unaffected by ethanol feeding. There was a statistically
significant increase in the ratio of myofibrillar/stromal synthesis rates (p
< 0.025) and a statistically significant decr in the ratio of sarcoplasmic/myofibrillar
synthesis rates (p < 0.05). There was also significant incr in the ratio of
myofibrillar/stromal absolute rates of protein synthesis.
Pregnant Sprague Dawley rats
were placed into the following treatment groups: control (water and lab chow ad
lib), 17% ethanol-derived calories (in liquid diet, 3.3% vol/vol), 35% ethanol
derived calories (6.7% vol/vol), 17% pair fed, and 35% pair fed. Pair fed
controls were fed the same volume of an isocaloric diet as was consumed by their
respective ethanol treated groups, with maltose dextrin to replace ethanol. The
pregnant female rats on the 17% ethanol diet consumed an avg of 10.8 g of
ethanol/kg body wt/day and maintained a relatively constant blood alcohol concn
of 40 mg% throughout gestation. 35% ethanol rats consumed an avg of 16.8 g
ethanol/kg. Their blood ethanol rose steadily during gestation reaching a
maximum of 170 mg% on the morning of day 18 of gestation. At birth, litters were
culled to 6 and cross fostered to untreated surrogate mothers. Radial arm maze
testing was initiated at 60 days of age and continued until the test criterion
was satisfied (2 adjacent error free trials). One half of the rats in the 35%
ethanol group did not reach criterion. The remainder of the 35% ethanol group
and the 17% ethanol rats attained criterion but required twice as many trials as
their respective pair fed controls. This difference was statistically
significant for the 35% ethanol group (p < 0.05). The total number of errors
committed prior to reaching the test criterion was elevated in both ethanol
treated groups compared to their pair fed controls, but the avg time required to
complete the maze per trial was reduced. Upon reaching criterion, there was very
little difference in maze running times between pair fed control and ethanol
treated groups.
Pregnant Sprague Dawley rats
were placed into the following treatment groups: control (water and lab chow ad
lib), pair fed, 10% ethanol derived calories, 20% ethanol derived calories, and
35% ethanol derived calories. The pair fed, 10% ethanol, 20% ethanol and 35%
ethanol groups were fed a liquid diet containing either 0%, 2%, 4%, or 6.7% vol/vol
ethanol, respectively. All the treatment groups received the same volume of an
isocaloric diet that was consumed by the 35% ethanol derived calories group.
Rats consumed an avg of 5.0, 10.0, and 16.8 g of ethanol/kg/day in the 10%,
20%,and 35% ethanol diets, respectively. Litters of alcohol treated mothers were
smaller, had more still births and had a higher number of pups which died within
2 days of birth (6.6%, 11.5%, and 30%, versus 4.7% for pair fed, p < 0.05)
than did the liters from the control mothers. At birth, litters were culled to
six and cross fostered to untreated surrogate mothers. There was a significant
effect of treatment on the body wt of pups at birth (p > 0.01). Pups in the
35% group were 4.13 g as compared to 6.27 g for the pair fed group. Pups were
sacrificed at 30 days of age and brains dissected into 8 regions. Each brain
region was homogenized and divided into soluble and membrane bound fractions by
centrifugation and digestion with deoxycholic acid. Treatment of the mothers
caused an incr in gamma-glutamyl transpeptidase activity associated with the
membrane bound fraction in the brains of newborn pups only at the 20% and 35%
ethanol levels. This incr was seen in all areas of brain examined (cerebellum,
pons-medulla, hypothalamus, midbrain, striatum, hippocampus, cortex, and frontal
cortex). In the midbrain and hypothalamus the activity was increased in a dose
dependent manner. The incr in gamma-glutamyl transpeptidase activity in some
areas of brain is maintained at least until the animals are 30 days old. Alcohol
treatment had no effect on the activity associated with the soluble form of
enzyme.
Long-Evans and Sprague-Dawley
male rats were given liquid alcohol diets containing 35%, 17.5%, or 0% ethanol
derived calories (EDC). The latter two groups were pair fed to the higher
alcohol diet group. A fourth group received lab chow and water ad libitum to
assess the role of paternal undernutrition associated with alcohol consumption.
After 3 or 4 wk of diet consumption, these males were bred to females of the
same strain. Pregnant females were divided into similarly treated alcohol groups
and were fed these diets beginning on gestation day 8, thus creating a factorial
study with strain, paternal, and maternal alcohol consumption as main factors.
Paternal alcohol consumption was associated with decr litter size, decr
testosterone levels, and a strain-related effect on offspring activity.
Offspring activity decr for those sired by 35% and 17.5% ethanol derived
calories Long Evans fathers. Activity also decr for offspring sired by 17.5%
ethanol derived calories Sprague Dawley fathers but incr for those sired by 35%
ethanol derived calories fathers. Paternal alcohol consumption did not affect
postnatal mortality or passive avoidance learning of offspring. Maternal alcohol
consumption was associated with lower birth wt, lower offspring wt at weaning,
incr postnatal mortality, and poorer passive avoidance learning. However,
offspring activity was not affected. In a separate study, levels of alcohol in
the testes were found to be somewhat, but not significantly, lower than blood
alcohol levels. DNA taken from sperm of Long Evans males consuming alcohol,
migrated farther under pulsed field electrophoresis than DNA from control
fathers, suggestive of an alcohol-related effect on sperm DNA.
To determine whether prenatal
exposure to ethanol alters the response of the beta-endorphin system to stress,
the effect of two types of stressful stimuli, ether and cold, was examined in
the offspring of rats which during pregnancy were: fed with an ethanol
containing diet (36% total calories of ethanol); pair-fed with an isocaloric
sucrose diet; and fed ad libitum with standard lab chow (basic control group).
The effect of stress on the content of beta-endorphin in the serum, pituitary
gland and hypothalamus, as well as on the serum corticosterone and hypothalamic
corticotropin-releasing factor (CRF) content was examined. Exposure to either
stress on day 14 elicited no response by the beta-endorphin system of the
ethanol exposed offspring. In contrast, the 22-day-old offspring of the ethanol
treated rats exhibited greater elevations in serum beta-endorphin and
corticosterone levels, following stress, than the offspring of the pair-fed and
basic control groups. The elevations of serum beta-endorphin levels following
stress were associated with small decr in the pituitary beta-endorphin and
hypothalamic CRF contents.
Marine diatoms (Skeletonema
costatum (Grev.) Cleve, 10,000 cells/ml) were exposed to a series of 5 or more
concn of ethanol for 5 days (replicated 3 times). 11,619 mg/l ethanol caused a
50% reduction in the number of cells per ml, and 10,943 mg/l caused a 50%
reduction in total cell volume. The no observed effect level (NOEL) was 5400
mg/l for total cell count and 3240 mg/l for total cell volume.
Hypothalami (from male
Sprague- Dawley rats) maintained in short term culture was exposed to ethanol.
After 90 min of preincubation, a 30-min incubation was conducted in low
potassium medium without ethanol. Next, depolarizing high potassium Krebs
Ringer's Phosphate buffer was used containing either no ethanol (n = 19) or
ethanol at concn of 50 mg% (n = 6), 100 mg% (n = 14), 200 mg% (n = 8) or 400 mg%
(n = 17). After 30 min the media was removed and analyzed for luteinizing
hormone-releasing hormone. In separate expt, either no ethanol or one high dose
of ethanol (400 mg%) was added to the initial, low potassium media. At the concn
tested, ethanol failed to inhibit luteinizing hormone-releasing hormone release
in vitro.
The acute (1 hr) effects of ip
injections of 4 concn (10%, 30%, 45% and 60%) of a single dose (0.5 g/kg) of
ethanol were investigated in groups of 10 unanesthetized male Wistar rats in an
open circuit calorimeter. After baseline measurement in the test chamber and ip
injection, rats were tested for an additional 60 min in the chamber. Every rat
received ethanol and saline at 4-day intervals. Ethanol increased energy
expenditure, with the greatest effect being produced by the two lowest concn.
However even the 45 and 60% concn had an effect on energy expenditure when time
after the injection was considered. In contrast, ethanol decr the respiratory
quotient, with the greatest effect being produced by the two highest concn. The
respiratory quotient of the control rats, after a small initial drop, quickly
stabilized and remained very constant over time, whereas those of the ethanol
treated rats declined progressively. Also, values for the 45% and 60% group were
significantly lower than that following the 10% and 30% injections. Ethanol had
only small and variable effects on motor activity. Treatment was significant
only at the 60% concn.
Groups of 6 rats were fed
alcohol (ethanol) for 6, 12 and 18 mo, while age matched controls were pair fed
sucrose. Additional groups were alcohol fed for 6 and 12 mo and then withdrawn
for 6 mo. The avg daily alcohol intake was 9 + or - 1.3 g/kg body wt, and no
significant differences were found in the mean body wt of alcohol fed rats and
controls. The numerical densities of the CA3 pyramidal cells and of the mossy
fiber-CA3 synapses of the hippocampal formation were calculated applying the
dissector method to adjacent sections of the CA3 pyramidal cell layer and the
stratum lucidum respectively. Results showed a progressive loss of pyramidal
cells in alcohol treated and withdrawal groups and a significant decr of mossy
fiber-CA3 synapses after 18 mo of alcohol feeding. A significant reduction was
found when the group alcohol fed for 12 mo and withdrawn for 6 mo was compared
with the 18 mo control group. No differences were detected when the group
alcohol fed for 6 mo and withdrawn for 6 mo was compared with age matched
controls. The percentage of mossy fiber plasmalemma occupied by postsynaptic
densities was significantly increased in the alcohol fed groups when compared
with respective controls. These data show that mossy fiber-CA3 synapses display
plastic and degenerative changes after chronic alcohol consumption and
withdrawal.
Groups (n = 6) of male Sprague
Dawley rats were given 10% ethanol (0.0, 1.0, 1.5, or 2.0 g/kg, ip, 15 min
before testing) for 2 sessions of baseline and 18 sessions of acquisition in a
radial maze. Each session consisted of 3 10-min trials of 8 rewards each.
Emptied food wells were immediately rebaited so that an entry into any arm
produced a reward of 2 food pellets. Ethanol produced a dose dependent reduction
in the variability of arm choice, of angle of turn between arms, and of goal
directed behavior. Correlations between these measures suggested they were not
independent.
To define further the
influence of ethanol on membranes, its effects on sodium ion (Na+) pump function
were studied in monolayer cultures of fetal rat hepatocytes. The effects of
ethanol (2 and 4 mg/ml) on total potassium ion (K+) influx, ouabain-sensitive K+
influx, Na+ pump density (from specific (3)H-ouabain binding), pump turnover
rates and intracellular Na+ were measured following exposure of the cells to
ethanol for 1-24 hr. In parallel studies, the effects of ethanol (2 mg/ml) on
cell water content and membrane fluidity were measured. Ethanol had no immediate
effect on K+ influx, but after 1 hr ethanol in concn of 2 and 4 mg/ml decr the
total K+ influx (uM/100 billion cells/sec) from a control of 8.5 + or - 0.64 to
4.46 + or - 0.50 and 4.09 + or - 0.26 respectively (N = 6 for each experiment).
This represented the max effect of ethanol since after 6 and 24 hr of ethanol
treatment the K+ influx had incr towards control levels but remained
significantly below that in control cells even at 24 hr. The decr in K+ influx
reflected a decr in mean ouabain-sensitive K+ influx from a control of 5.87 to
3.24 and 2.70 (uM/100 billion cells/sec) after a 1-hr treatment with 2 and 4 mg
ethanol/ml medium, respectively. Ethanol (2 mg/ml) treatment for 1 hr decr Na+
pump density (x 100,000 molecules ouabain per cell) from a control of 2.80 + or
- 0.30 to 1.70 + or - 0.11 (p < 0.001). At 6 and 24 hr (3)H-ouabain binding
showed a pattern similar to that seen with the K+ influx, tending to return to
pretreatment levels. There was no change in individual pump turnover rates in
the presence of ethanol. Following exposure to ethanol, cellular Na+ content
steadily incr over the first 6 hr and then returned to control levels. When
corrected for parallel changes in cell vol, intracellular Na+ concn incr by 17%
(p < 0.01) after 1 hr and thereafter remained at this higher level throughout
the 24 hr period. Measurements of membrane fluidity showed that it was incr
markedly by ethanol at a concn of 2 mg/ml and that the effect bore a close
temporal relationship to the changes in active K+ influx and Na+ pump density.
In a first expt, 11-day old
pups received intragastric ethanol admin (1.5 g/kg). At different postabsorptive
intervals, footshock was presented (0 to 30, 30 to 60, 60 to 90, or 90 to 120
min; n = 12 to 13 per group). An explicitly unpaired control group which
experienced footshock prior to the state of intoxication was also employed. All
animals were subsequently tested in terms of alcohol intake and ethanol
locational odor preferences. Pups which suffered shock 1 to 30 or 30 to 60 min
after ethanol intragastric admin exhibited lower ethanol intake scores than
those recorded for the remaining groups. Mice which experienced shock 30 to 60
min after being inoculated with alcohol, also exhibited lower ethanol olfactory
preference scores than those registered in the remaining groups. In a second
expt, groups of 9 to 11 pups were exposed to footshock during the postabsorptive
interval. 24 hr later, pups experienced ambient ethanol odor paired with soft
(cotton) or rough (sandpaper) texture surfaces. Differential texture aversions
were registered in exptl animals when compared with controls which suffered the
state of intoxication explicitly unpaired with footshock, or unpaired
presentations of ethanol odor and the tactile stimuli under consideration.
Ethanol produced a decr in the value of a given texture when the 2 stimuli were
paired.
Neonatal rats were exposed to
6.6 g/kg of alcohol (ethanol) each day between postnatal days 4 and 10 while
artificial rearing procedures were used, in a manner which produced high peak
and low trough blood alcohol concn each day. Gastrostomy controls were reared
artificially with maltose/dextrin isocalorically substituted for alcohol in the
milk formula, and suckle controls were reared normally by dams. The pups were
sacrificed on day 10 and tissue sections (2 um thick were obtained in the
sagittal plane through the cerebellum and in the horizontal plane through the
hippocampal formation. Overall area measures were obtained for the hippocampus
proper, area dentata, and cerebellum, along with areas of the cell layers of
these regions. In the hippocampal formation, cell counts were made of the
pyramidal cells of the hippocampus proper, the multiple cell types of the hilus,
and the granule cells of the granular layer, granule cells of the external
granular layer, and mitotic cells of the external granular layer were obtained
from lobules I, V, VII, VIII, and IX. Alcohol selectively reduced areas and
neuronal numbers in the cerebellum but had no significant effects on neuronal
numbers in the hippocampal formation. Purkinje cells exhibited the greatest
percent reductions, and cerebellar granule cells were significantly reduced in
the granular layer but not in the external granular layer. All lobules showed
these effects, but lobule I was significantly more affected than the other four
lobules that were analyzed.
The specific activities of
testicular postmeiotic enzyme markers such as sorbitol dehydrogenase (SDH),
lactate dehydrogenase (LDH), and alpha-glycerophosphate dehydrogenase (GDH) that
incr with age were used as a biochemical measure of testicular development in
CFW mice treated with ethanol (3% vol/vol) via liquid diets from ages 20 to 55
days of life. Chronic ethanol treatment resulted in decr activities of sorbitol
dehydrogenase and lactate dehydrogenase at ages 40 and 44 days, and of
glycerophosphate dehydrogenase at ages 34, 40,and 44 days. These decr were
consistent with an arrest in the developmental incr in sorbitol dehydrogenase,
lactate dehydrogenase, and glycerophosphate dehydrogenase at ages 31 + or - 0.6,
31 + or - 2.6, and 25 + or - 0.5 days, respectively. After 29 days of ethanol
treatment (age 50 days), testicular wt, epididymal sperm content, and sperm
motility were reduced, relative to controls, by 37, 83, and 60%, respectively (p
< 0.05). Light microscopic evaluation of testes revealed disorganization of
spermatogenesis, germ cell degeneration, decr tubular luminal diameter, and
vacuolation of Sertoli cells in ethanol-treated mice at age 50 days. Electron
microscopic analysis showed that germ cell degeneration was not restricted to a
specific cell type. Stage IX-XI tubules were observed in which spermatids had
been retained and underwent phagocytosis within the Sertoli cell. Sertoli cells
showed evidence of atypical nuclear invaginations. Sertoli cells underwent
degenerative changes and were sloughed into the rete testis.
Twenty three 6-8 wk old male
and female mice of various strains (Swiss, Balb/c, DBA/2, CBA, C57B1/6, and
B6D2F1) received a topical application of a 95% solution of ethanol on both
sides of the right ear on days 0 and 2, and a scapular sc injection of 0.05 ml
of complete Freunds adjuvant on day 2. On day 9, left ear thickness was measured
immediately before topical application of 95% ethanol (the maximal nonirritating
concn), on both sides of the ear, and again 24 hr later (day 10). No
statistically significant incr in ear thickness was seen. In another test
procedure, anesthetized male (n= 9) and female (n= 10) Swiss mice received a sc
injection of 0.05 ml of ethanol in complete Freunds adjuvant into the scapular
region, together with a topical application of ethanol on the shaved abdomen. On
days 3, 5, 7, 10, 12, and 14 they received a topical application on the shaved
abdomen and a second scapular sc injection of 0.05 ml complete Freunds adjuvant
on day 7. On day 26, left ear thickness was measured immediately before a
topical application of ethanol on both sides of the ear. Left ear thickness was
again measured on days 27 (24 hr after challenge) and 28 (48 hr later). No
significant incr in ear thickness was seen.
Non-Human Toxicity Values:
LD50 Rat oral 13.7 ml/kg
LD50 Rabbit oral 12.5 ml/kg
Ecotoxicity Values:
LC50 PALAEMONETES > 250
MG/L/96 HR @ 21 DEG C, MATURE /STATIC BIOASSAY/
LC50 SALMO GAIRDNERII (RAINBOW
TROUT) 13000 MG/L/96 HR @ 12 DEG C (95% CONFIDENCE LIMIT 12000-16000 MG/L), WT
0.8 G /STATIC BIOASSAY/
LC50 Pimephales promelas
(fathead minnows) 15.3 g/l/96 hr (95% confidence limit 14.0-16.6 g/l); age 30
days old, water hardness 47.3 mg/l (CaCO3), temp 24.3 deg C, pH 7.60, dissolved
oxygen 6.8 mg/l, alkalinity 43.7 mg/l (CaCO3); tank vol: 6.3 l; additions: 3.81
vol/day /Flow-through bioassay/
EC50 Pimephales promelas
(fathead minnows) 12.9 g/l/96 hr; age 30 days old, water hardness 47.3 mg/l
(CaCO3), temp 24.3 deg C, pH 7.60, dissolved oxygen 6.8 mg/l, alkalinity 43.7
mg/l (CaCO3); tank vol: 6.3 l; additions: 3.81 vol/day /Flow-through bioassay/
LC50 Pimephales promelas
(fathead minnows) 14.2 g/l/96 hr (95% confidence limit 13.4-15.1 g/l); age 30
days old, water hardness 47.5 mg/l (CaCO3), temp 24.0 deg C, pH 7.56, dissolved
oxygen 6.6 mg/l, alkalinity 40.9 mg/l (CaCO3); tank vol: 6.3 l; additions: 4.5
vol/day /Flow-through bioassay/
Toxicity Threshold (Cell
Multiplication Inhibition Test) Scenedesmus quadricauda (green algae) 5000 mg/l
Toxicity Threshold (Cell
Multiplication Inhibition Test) Microcystis aeruginosa (algae) 1450 mg/l
Toxicity Threshold (Cell
Multiplication Inhibition Test): Uronema parduczi Chatton-Lwoff (protozoa) 6120
mg/l
Toxicity Threshold (Cell
Multiplication Inhibition Test) Entosiphon sulcatum (protozoa) 65 mg/l
Toxicity Threshold (Cell
Multiplication Inhibition Test) Pseudomonas putida (bacteria) 6500 mg/l
Ongoing Test Status:
The NTP Toxicology Research
and Testing Program releases a Management Status Report on a quarterly basis.
This report gives the status of chemicals studied, under study, or proposed for
study by NTP. The 07/11/2001 issue indicates that the laboratory study report in
preparation of the two year study for ethanol is in progress. Route: dosed-water
feed; Species: mice.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
NINETY TO 98% OF ALCOHOL THAT
ENTERS THE BODY IS COMPLETELY OXIDIZED. ... AMT ... OXIDIZED PER UNIT OF TIME IS
ROUGHLY PROPORTIONAL TO BODY WT & PROBABLY TO LIVER WT. IN ADULT, AVG RATE
AT WHICH ALCOHOL CAN BE METABOLIZED IS ABOUT 30 ML IN 3 HR. ... MAXIMAL DAILY
METABOLISM OF ALCOHOL IS ABOUT 450 ML /IN MAN/. ... INITIAL OXIDATION OF ALCOHOL
OCCURS CHIEFLY IN LIVER ... PRIMARY STEP IS OXIDATION ... TO ACETALDEHYDE BY
ALCOHOL DEHYDROGENASE ...
Male rats were given four
consecutive hourly doses of ethanol at 1 g/kg to study the effects of ethanol on
urinary excretion of folates. At 5 hours tritium labeled folic acid was
administered and urine samples collected for 1 hour. At 6 hours rats were
sacrificed with collection of plasma, liver, and kidney samples. A significant
increase in the urinary excretion of endogenous folates occurred in ethanol
treated rats at both the 4 to 5 hour and 5 to 6 hour periods, but no significant
increase in tritium labeled derivatives was noted in ethanol treated rats. The
predominant tritium labeled folic acid metabolites in urine were
5-formimimotetrahydrofolic acid and the formyl tetrahydrofolates whereas the
major endogenous form was 5-methyltetrahydrofolic acid. Ethanol administration
significantly increased the excretion of the methyl derivative, with minor
effects on the other folate forms. The amount of endogenous folate present with
each of the tissues (plasma, kidney, and liver) was not altered by ethanol
treatment except for a significant increase in plasma folate in ethanol treated
rats at 5 hours. The amount of tritium labeled folate derivatives within each of
these tissues did not show any differences between ethanol and control
treatments. In plasma, the major folate form was 5-methyltetrahydrofolic acid
with a small amount of 5 and 10-formyltetrahydrofolic acid; the tritium labeled
forms were predominantly 5-methyltetrahydrofolic acid and folic acid. In the
kidney the predominant endogenous folate was 5-methyltetrahydrofolic acid (about
80% of total) with smaller amounts of the formyl and tetrahydrofolic acid
derivatives; the major tritium labeled folate derivatives were
5-methyltetrahydrofolic acid and folic acid. In liver, endogenous folate levels
were much higher than in kidney. Of the endogenousfolates in liver,
5-methyltetrahydrofolic acid represented the largest portion (about 50%) but
tetrahydrofolic acid and the formyl derivatives also were present in large
amounts; the major tritium labeled derivative was folic acid (60 to 80%).
METABOLISM OF ETHANOL,
PROPANOL, ISOPROPANOL, BUTANOL, ISOBUTANOL, SEC-BUTANOL, & TERT-BUTANOL WAS
STUDIED AFTER ORAL ADMIN IN RABBITS. BLOOD PH WAS ON THE ACID SIDE WITH PROPANOL,
BUTANOL, & ISOBUTANOL, AND ON THE ALKALINE SIDE WITH ISOPROPANOL & SEC-BUTANOL,
BUT NO CHANGE WAS OBSERVED WITH ETHANOL & TERT-BUTANOL. BUTANOL &
ISOBUTANOL HAD THE LOWEST RATE OF URINARY EXCRETION. ACETALDEHYDE AND ACETIC
ACID WERE DETECTED AS THE URINARY METABOLITES OF ETHANOL AND PROAPNOL, WHEREAS
ISOBUTYRALDEHYDE & ISOVALERIC ACID WERE THE METABOLITES OF ISOBUTANOL.
The alcohol dehydrogenase
pathway probably is the major pathway of ethanol oxidation in the body.
Conversion of ethanol to acetaldehyde by alcohol dehydrogenase is the rate
limiting step. Both alcohol and aldehyde dehydrogenase require NAD, which
reduces the hepatic NAD/NADH ratio. The shift in this ratio changes the cytosol
redox potential and causes profound metabolic abnormalities in chronic
alcoholics. The final step is conversion of acetate to acetyl CoA and then
carbon dioxide and water via the Krebs cycle.
Results of research in
alcoholism show great inter-individual, as well as racial, variability in
metabolism of alcohol and acetaldehyde. The hypothesis is put forward that the
individual and racial differences in alcohol metab are based on the genetically
determined variability of the participating enzymes, alcohol dehydrogenase and
aldehyde dehydrogenase. In Orientals lacking the mitochondrial low Km aldehyde
dehydrogenase, acetaldehyde accumulates and produces symptoms of intoxication.
Blood concn of ethanol and
acetaldehyde were determined in suckling Wistar rats after a single oral ethanol
gavage. These results were compared with the hepatic activities of alcohol and
aldehyde dehydrogenase. After intragastric administration of 3 g/kg body wt of
ethanol, ethanol concn were much higher in suckling rats than in adult animals,
especially at 90, 120, and 180 min after its administration. In addition,
acetaldehyde concn were undetectable in suckling rats as opposed to adult rats,
in whom micromolar concn were detected. Analysis of hepatic alcohol
dehydrogenase activity revealed that it was very low at birth and it incr
progressively with time attaining adult levels after 20 days of life. The
alcohol dehydrogenase activity present in the liver of suckling rats presented
similar Km values and sensitivity to pyrazole as adult rat liver. At birth,
hepatic aldehyde dehydrogenase activity was low and it incr reaching adult
levels during the suckling period. Adult levels for the component of low Km were
attained earlier than for the component of high Km. The low affinity hepatic
aldehyde dehydrogenase component in the newborn was different from that in the
adult as assessed by kinetic studies and by its sensitivity to disulfiram.
Brain samples from rats
genetically selected for high or low voluntary alcohol (ethanol) intake (AA and
ANA strains) or for differences in alcohol induced motor incoordination (AT and
ANT strains) were analyzed by histochemistry for aldehyde dehydrogenase (EC
1.2.1.3) activity in various CNS structures. All strains exhibited the highest
aldehyde dehydrogenase activities in neurons of the mesencephalic tract of
trigeminal nerve nucleus and in spinal cord motoneurons, while the lowest
activities were observed in the somatosensory cortex. Although the general
distribution pattern of aldehyde dehydrogenase activity was similar in the
genetically selected strains, some potentially important differences were
observed. AA rats with high voluntary alcohol consumption had lower aldehyde
dehydrogenase activity (with acetaldehyde as substrate) in the neuropil of the
olfactory tubercle but higher activity (with benzaldehyde as substrate) in the
spinal cord motoneurons, Purkinje cells and capillary endothelium of the
cerebellum as compared to the corresponding structures from the alcohol avoiding
ANA rats. Alcohol resistant AT rats had higher aldehyde dehydrogenase activity,
with benzaldehyde, in most CNS structures than did the alcohol sensitive ANT's,
significantly so in the lamina II of the somatosensory cortex and the neurons of
the lateral hypothalamic area. This relationship was also found with
acetaldehyde as substrate in the neurons of the hypothalamic arcuate nuclei and
in cerebellar capillaries, but the ANT's had the higher activity in the neurons
of the cerebral cortex V lamina.
The activities of aldehyde
dehydrogenase and alcohol dehydrogenase were measured in term placentas of 13
alcoholic women (avg ethanol consumption > 50 g/day) and 16 matched controls.
With acetaldehyde 8 mM/l as substrate, the aldehyde dehydrogenase activity was
29.1 + or - 12.2 and 34.4 + or - 15.3 mU/g of wet wt (mean + or - SD) for
alcoholics and controls, respectively. With 50 uM of acetaldehyde, aldehyde
dehydrogenase activity was undetectable in both groups. No alcohol dehydrogenase
activity could be detected in the placentas. The wt of placentas and newborns
were significantly lower in the alcoholic group (placentas: 526 + or - 116 vs.
653 + or - 77 g, newborns 2,878 + or - 417 vs. 3,595 + or - 346 g).
Ethanol (2 g/kg) was
administered via a liquid diet (36% ethanol) to fed Sprague-Dawley rats
concomitantly with nutrients and to fasted rats without nutrients. When
nutrients were intubated concomitantly with ethanol there was significant
first-pass or presystemic ethanol metabolism by both the gastrointestinal mucosa
and the liver. When ethanol was intubated without other nutrients first-pass
metabolism was not detectable in fasted rats at this high ethanol dose.
Absorption, Distribution & Excretion:
ALCOHOL IS RAPIDLY ABSORBED
FROM STOMACH, SMALL INTESTINE, & COLON. VAPORIZED ALCOHOL CAN BE ABSORBED
THROUGH LUNG ... AND FROM SUBCUTANEOUS SITES ... ABSORPTION OF ALCOHOL THROUGH
HUMAN SKIN IS NEGLIGIBLE. ... ALCOHOL IS FAIRLY UNIFORMLY DISTRIBUTED THROUGHOUT
ALL TISSUES & ALL FLUIDS OF THE BODY. PLASMA CONCN IS SOMEWHAT HIGHER THAN
THAT IN ERYTHROCYTES. PLACENTA IS PERMEABLE TO ALCOHOL; THUS, ALCOHOL GAINS FREE
ACCESS TO FETAL CIRCULATION ... AMT OF ALCOHOL IN BRAIN OF PERSONS DYING OF
ALCOHOLIC INTOXICATION VARIES FROM 300 TO 600 MG/100 G /OF TISSUE/. ALCOHOL IS
ALSO PRESENT IN CEREBROSPINAL FLUID, @ CONCN LOWER THAN THAT IN BLOOD WHEN THE
BLOOD CONCN IS RISING AND HIGHER WHEN THE BLOOD CONCN IS FALLING.
NORMALLY ABOUT 2% OF INGESTED
ALCOHOL ESCAPES OXIDATION ... WHEN LARGE DOSES OF ALCOHOL HAVE BEEN CONSUMED
THIS VALUE MAY BE AS HIGH AS 10%. ALTHOUGH SMALL AMT OF ALCOHOL CAN BE DETECTED
IN VARIOUS SECRETIONS, MOST OF THE ALCOHOL THAT ESCAPES OXIDATION IS EXCRETED
THROUGH THE KIDNEYS & LUNGS. ... THE CONCN IN THE URINE IS SLIGHTLY GREATER
THAN, AND THE CONCN IN THE ALVEOLAR AIR ONLY 0.05%, THAT OF THE BLOOD.
The distribution of alcohol
between alveolar air and blood depends on its speed of diffusion, and its vapor
pressure at the prevailing temp & concn of alcohol in the lung capillaries.
Empirical determinations have yielded rather different values for this
distribution ratio, but a commonly accepted value is 1:2100.
Venous blood (orbital sinus)
and brain ethanol levels were measured in long sleep and short sleep mice within
the first 30 min following ethanol administration (2.5 to 6.0 g/kg). Ethanol was
administered ip or intragastrically. For both lines of mice and for every dose,
brain ethanol concentrations were significantly greater (as much as 100 mg/dl)
than blood ethanol levels for the first 6 min, and peak blood and brain ethanol
levels were reached 4 to 6 min after dosing. Approx 6 to 10 min (depending on
dose and line of mouse) was required for blood and brain concn to reach
equilibrium. At the time of loss of the righting response brain ethanol levels
were significantly higher than blood ethanol levels. These results indicate that
within the first 6 min after administration of ethanol, blood ethanol level is
not suitable for the assessment of brain ethanol content.
The method of Pohorecky and
Brick was modified for determination of ethanol concn in rebreathed air of rats.
Female Sprague Dawley rats were injected with different doses (1 to 2 g/kg) of
ethanol and both arterial blood and rebreathed air samples were collected at
various time intervals (15 to 120 min) after administration. A good correlation
(r= 0.96) was found between ethanol concn in arterial blood and in rebreathed
air; the blood/breath conversion factor was 3241 + or - 55. Rats that were
trained to discriminate between ip administered ethanol (1.2 g/kg) and the
saline vehicle (12 mg/kg) were given different doses (0.5, 0.9 and 1.2 g/kg) of
ethanol and were examined at various time intervals (1, 7.5, 15, 30, 60, 120 and
240 min) after administrations on certain test days. The results indicate a good
correlation (r= 0.65) between the discriminative stimulus effects of ethanol and
the concn measured in rebreathed air. The behavioral effects as well as the
concn of ethanol in rebreathed air have a fast onset. The peak occurred 7.5 min
after injection, and both the stimulus effects and concn of ethanol were time
and dose dependent.
Delipidized stratum corneum
was prepared from male human dorsal skin from skin banks. Previously weighed
stratum corneum, delipidized stratum corneum, and hydrogels (prepared from
polytetramethylene oxide and 2-hydroxyethylmethacrylate) were equilibrated with
aqueous ethanol solutions of varying volume fractions of ethanol at 32 deg C for
24 hr. There is a broad maximum in the ethanol uptake into stratum corneum from
0.2 to 0.85 volume fraction of ethanol. The maximum ethanol uptake is roughly
equivalent to the dry stratum corneum in wt. At an ethanol volume fraction of
1.0 there is a dramatic decr in ethanol uptake to 99 + or - 7 ug ethanol/mg
stratum corneum. Dehydration and shrinkage of the stratum corneum largely
reduces ethanol uptake in spite of the incr in ethanol driving force. Ethanol
uptake into delipidized stratum corneum exhibits a sharp maximum at an ethanol
volume fraction of 0.7. Using triolein as a simple lipid model, a linear
cosolvency was observed with ethanol:triolein mixtures. There was no optimum for
solubility in triolein. A model is proposed which qualitatively predicts the key
features of ethanol enhanced skin permeation on the basis of these solubility
phenomena and a constant diffusion coefficient.
The rate of ethanol
elimination was studied in two groups of men by means of an Alcotest 7010(TM)
breath analyzer. The exptl group consisted of 15 skid row alcoholics undergoing
detoxification. Their median daily ethanol consumption was 211 (range 26 to 476)
g pure ethanol during the last year. The control group was made up of 12 age
matched healthy social drinkers consuming 9 (range 4 to 23) g/day pure ethanol
during the last year. The median ethanol elimination rate in the elimination
phase was 0.25 (range 0.13 to 0.31) g/l/hr during the detoxification period in
the exptl group. This value was approximately 70% higher than in the control
group (0.14 (0.12 to 0.17) g/l/hr. The alcoholic group had significantly higher
values for gamma glutamyl transferase, alanine amino transferase, aspartate
amino transferase, glutamate dehydrogenase, creatinine kinase, alkaline
phosphatase, and HDL cholesterol, and lower urea, creatinine, and osmolality
values in serum. Erythrocytes were lower and mean corpuscular volume was higher
in the exptl group. Some correlation was found between reported ethanol intake,
and the calculated ethanol elimination rate, as well as gamma glutamyl
transferase, alanine amino transferase, aspartate amino transferase, glutamate
dehydrogenase, mean corpuscular volume and HDL cholesterol.
Urine was analyzed
immediately, 1, 2, 8, and 9 hr after drinking (during 2 hr) 3.75 ml/kg of
beverages containing orange juice, 15 or 40% ethanol, and and 1 g/l of
1-propanol, 2-propanol, 1-butanol, 2-butanol, isobutyl alcohol or a mixture of
1-propanol & isobutyl alcohol. Maximum urine levels /in mg/l/ were found 1
hr after drinking ended: 1-propanol 5.04, 2-propanol 3.36, 1-butanol 0.43,
2-butanol 2.55, isobutyl alcohol ... 1.7-2.03 mg/l. Urine treatment with beta-glucuronidase
before analysis indicated that significant amounts of the alcohols were excreted
as glucuronides, esp isobutyl alcohol. 2-Propanol and 2-butanol were the slowest
to be metabolized. When mixtures of alcohols were given, the concentrations of
isobutyl alcohol glucuronides were high with the mixtures containing 5 and 15%
ethanol, and decreased at 40% ethanol.
The small intestine extracts
about 80% of an oral ethanol dose; the stomach absorbs the remainder. ... In
healthy adults, 80%-90% of absorption occurs within 30-60 min, but food may
delay complete absorption for 4-6 hr.
Alcohol equilibrates rapidly
between blood and milk; milk levels are about 90-95% of simultaneous blood
levels.
Ethanol is present as an
endogenous substance in the blood of man, probably produced in the intestinal
tract, at an avg level of 1.5 mg/l. Resting subjects developed blood concn of
less than 100 mg/l when exposed to vapor concn of 7500-8500 ppm for 3 hr, while
an exercising subject developed a blood level of 450 mg/l under the same
conditions. A single oral dose of 0.5 ml/kg (35 ml/70 kg) of pure ethanol given
to 4 fasting men produced an avg maximal blood concn of about 400 mg/l at 2 hr;
a dose of 1.4 mg/l (98 ml/70 kg) produced a level of 1200 mg/l at 1 hr; and 2.0
ml/kg (140 ml/70 kg), a level of 2000 mg/l at 1 hr. The levels declined at a
mean rate for the 21 subjects of 189 mg/l/hr.
About 95% of a dose undergoes
metabolism and the remainder is excreted unchanged in the breath, urine, sweat
and feces.
Pregnant Hartley guinea pigs
were orally admin either 2 daily doses of 1 g ethanol/kg maternal body wt (n= 7)
or isocaloric sucrose solution (n= 6) on days 1 through 59 of gestation (term=
66 days). The doses, given 2 hr apart, produced a maternal blood ethanol concn
of 27.6 + or - 3.0 mM at 1 hr after the second ethanol dose, as assessed at 55
days of gestation. The activity of alcohol dehydrogenase, low K sub m aldehyde
dehydrogenase, and high K sub m aldehyde dehydrogenase activities in the
maternal liver, fetal liver, and placenta was determined spectrophotometrically
at day 59 of gestation. None of these enzyme levels were statistically different
for the 2 groups. This was also the case for the maternal blood and fetal blood
ethanol and acetaldehyde concn, determined at 2 hr after maternal admin of 1 g
ethanol/kg maternal body wt. There was no exptl evidence of ethanol induced
malnutrition in the mother or growth retardation in the fetus. No statistical
differences in the reproductive data, average daily food consumption, and
maternal and fetal body and organ wt were found. There was a statistically
significant incr (65%, p < 0.05) in the microsomal cytochrome p450 content of
the maternal liver for the ethanol treatment compared with the sucrose
treatment.
6 conscious and instrumented
near-term pregnant ewes (135 to 140 days gestation) were given iv infusion of 3
g ethanol/kg total body wt admin as 6 doses of 0.5 g/kg over 8 hr. Maternal and
fetal blood ethanol concn, determined in 2 animals, were maximal at 8 hr (3.74
and 3.82 mg/ml, respectively) and were virtually identical during the 24 hr
study. Maternal and fetal blood gases (PO2, PCO2, or absolute base excess (ABE))
and acid-base balance (pH) were not significantly altered during and after
ethanol admin compared with preinfusion values. There was also no change in
fetal arterial blood HCO3 -1 or hemoglobin compared with control. Ethanol was
not measurable in maternal and fetal blood 24 hr after the last ethanol dose.
Male human subjects (150,
19-30 yr of age) were given ethanol orally as vodka (0.55, 0.7, or 0.85 g/kg)
followed by a second drink (0.3-0.4 g/kg) 3-4 hr later. After both doses, blood
ethanol levels reached approx 100 mg/dl. Breath samples were taken every 20-30
min and rates of ethanol elimination were determined. In addition to the design
described above, 100 subjects received 0.7 g/kg ethanol in 2 separate visits to
the laboratory. In a third experimental design, ethanol was given iv to 12
subjects at an initial dose of 0.45 g/kg/30 min until breath ethanol levels
reflected blood levels of approx 50 mg/dl. With the single-day experimental
design, the frequency distribution of changes in rates of ethanol elimination
between the first compared with the second administration of ethanol was not
unimodal. Up to 20% of the subjects demonstrated rates more than 40% greater
than basal values in response to ethanol. Based on these findings in humans, a
Swift incr in Alcohol Metabolism (SIAM) was defined as an incr in the rate of
ethanol elimination of at least 40% over the basal rate. Under these conditions,
the frequency of Swift incr in Alcohol Metabolism was dose dependent (studied
with 0.55, 0.7, and 0.85 g/kg); nearly 20% of the subjects demonstrated Swift
incr in Alcohol Metabolism with a dose of ethanol of 0.85g/kg. In the 2-day
experimental design, a Swift incr in Alcohol Metabolism response was also
observed in about 10% of 49 well-fed subjects; however, none of 51 subjects
tested exhibited a Swift incr in Alcohol Metabolism response following an
overnight fast. In addition, a rapid and transient Swift incr in Alcohol
Metabolism reflecting a 60% incr in the rate of ethanol elimination above basal
values was observed when ethanol was given continuously for 5 hr iv.
Groups of 36 adult rats (18
males and 18 females) belonging to either UChA or UChB strains were exposed to
either air (control group) or ethanol vapor (6 to 7 mg/l) during 46 hr in an
inhalation chamber. Each group was further distributed into 4 subgroups
according sex and strain (9 rats per each subgroup). Ethanol blood levels were
measured during day 2 of exposure. 6 hr after exposure, rats from both groups
received 60 mmoles/kg ethanol ip. Blood alcohol level data showed no significant
difference by strain, but a marked difference according to sex. The mean blood
alcohol level of females was 196 + or - 27 mg/dl and that of males was 114 + or
- 22 mg/dl (p < 0.05). No significant difference in latency time (interval
between injection and loss of righting reflex) was observed by treatment, sex or
strain. The difference between /SRP: CNS depression/ time for control and exptl
rats was significant for all groups, ie, 142 vs 42 min for female UChA (p <
0.001); 167 vs 51 for male UChA (p < 0.001); 91 vs 25 for female UChB (p <
0.005); 128 vs 55 for male UChB (p < 0.005). There was a significant
difference of strain in the control group (p < 0.01) and of sex in the exptl
group (p < 0.05). Data concerning blood alcohol at awakening after ip ethanol
show a difference significant only at the 0.05 level, between exptl and control
for males of the UChA strain. Data on the decr of rectal temp reveals no
difference between treated and control rats, with the exception of the UChB
males, which exhibited a slightly lower hypothermia, significant at the 0.05
level.
Groups of 12 selectively bred
high alcohol drinking and low alcohol drinking adult male rats (S8 generation)
were tested over a 4 wk period for the free choice consumption of 10% (v/v)
ethanol in the presence of ad lib food and water. 12 rats from each line were
also given food and water ad lib (controls). Rats of the high alcohol drinking
line (n = 30) consumed 5.6 + or - 0.4 g ethanol/kg/day, and low alcohol drinking
rats (n = 31) averaged 1.0 + or - 0.2 g/kg/day. Compared with the low alcohol
drinking line, the contents of serotonin and/or 5-hydroxyindoleacetic acid were
approx 10 to 20% lower in several brain regions of the high alcohol drinking
line (cerebral cortex, striatum, nucleus accumbens, septal nuclei, hippocampus
and hypothalamus). The levels of dopamine, 3,4-dihydroxyphenylacetic acid and
homovanillic acid were also 10 to 20% lower in the nucleus accumbens and
anterior striatum of the high alcohol drinking animals.
Rates of ethanol elimination
(after iv admin of 0.6 g ethanol/kg) were determined in 4 hypogonadal pt at 1 wk
and again at 8 wk after the admin of 1 dose of 200 mg of testosterone cypionate
(Depo-testosterone). Ethanol elimination was unchanged in 2 pt, slightly decr in
1, and markedly increased in 1 pt at 8 wk as compared to 1 wk after testosterone
admin. In the 3 pt with little or no change in ethanol elimination, initial high
levels of plasma free testosterone, ranging from 445.0 to 3.8 ng/dl did not decr
to abnormally low levels, but ranged between 1.6 and 7.7 ng/dl (normal = 1.20 to
2.10 ng/dl). In the fourth pt, an incr in ethanol elimination from 86.6 to 107.4
mg/kg body wt/hr was associated with a decr in plasma free testosterone from a
high level of 4.7 to 0.8 ng/dl. Admin of testosterone had no effect on peak
ethanol concn after ethanol infusion or on the apparent vol of distribution of
ethanol.
The effects of 3 variations in
meal composition (a solid and a liquid meal consumed together, a liquid meal
consumed alone, and a liquid meal consumed 90 min after a solid meal) on the
rates and patterns of solid and liquid gastric emptying were examined in 13
volunteers. By including alcohol (0.5 g/kg body wt) in the liquid meal, the
relationship between alcohol absorption and gastric emptying was also assessed.
The lag phase and the initial emptying phase of the solid meal were prolonged
when the liquid meal was consumed with the solid meal, compared with when the
liquid meal was consumed 90 min after the solid meal. In this latter situation,
consumption of the liquid meal caused the cessation of emptying of solid food,
and this second lag phase was followed by a slower than initial emptying phase.
Gastric emptying of the liquid meal was slower when solid food was present and
was slowest when liquid was consumed 90 min after the solid meal. Alcohol
absorption was fastest when the liquid meal was consumed alone and slower when
alcohol was consumed with or after the solid meal. For all three meals there was
a close correlation ( r > or = 0.91) between alcohol absorption and liquid
emptying.
A 30-mo old, 13-kg child
reportedly ingested up to 16 oz of a wine containing 20% ethanol. The child was
brought into the emergency department by paramedics, and upon arrival was found
to be comatose and unresponsive to deep stimuli but breathing spontaneously. The
pt remained unconscious and unresponsive for 3 hr after admission. The child was
discovered at about 9 am by his mother. Blood ethanol and blood glucose levels
were 98.78 and 22.14 mmol/l at 10:20 am; 84.45 and 24.31 at 1:40 pm; 52.10 and
23.88 at 6 pm, respectively. At 8:31 the next morning there was no detectable
amount of ethanol in the blood. Recovery was complete without sequelae.
Treatment consisted of prompt gastric decontamination and maintenance of
adequate hydration and euglycemia. Elimination of ethanol was rapid and appeared
to follow first order kinetics instead of the zero order kinetics usually
observed. No significant metabolic or cardiorespiratory derangement occurred.
The distribution of
maternally-derived glucose was determined in selected tissues of fetuses from
ethanol-fed (EF) Sprague Dawley rats and from pair-fed (PF) and ad lib-fed (AF)
controls. The ethanol-fed group was given unrestricted access to liquid diet, in
which 30% of the calories were derived from ethanol. Maternal ethanol ingestion
resulted in reduced fetal brain and liver wt and lower liver and lung glycogen
levels compared to those of the pair-fed or ad lib-fed control groups. In
addition, ethanol-fed fetuses exhibited reduced uptake of maternally-derived
(3)H-2-deoxy-D-glucose (2DG) by placenta and fetal brain. Fetal body, liver,
lung, and brain wt correlated with fetal plasma 3H activity and with the
fetal:maternal plasma 3H ratio, an indicator of the rate of placental glucose
transfer. Brain wt correlated with 2-deoxy-D-glucose content/g tissue wt.
Female Fischer 344 rats, aged
4, 14, and 25 mo, received 4.0 g/kg ethanol by ip injection. Blood alcohol concn
after ethanol injection were 0.42, 0.50, and 0.52% at 2.5 hr, 0.40, 0.40, and
0.39% at 6 hr and < 0.0005 at 16 hr for 4, 14, and 25 month old rats,
respectively. Hepatic glutathione levels were diminished 6 hr after ethanol
injection and there were no age-dependent differences in the depleted levels
(3.2 + or - 0.1, 3.5 + or - 0.2, and 3.0 + or - 0.5 ug glutathione/g liver).
However, glutathione contents in livers of young-adult rats approached control
levels after 16 hr, whereas they remained depressed in older rats. Serum levels
of hepatic enzymes were significantly elevated 6 hr after ethanol admin. The
incr were greater in middle-aged and old rats than in young-adult rats.
Mechanism of Action:
... ALCOHOL ... IS A PRIMARY
AND CONTINUOUS DEPRESSANT OF THE CNS. THE APPARENT STIMULATION RESULTS FROM THE
UNRESTRAINED ACTIVITY OF VARIOUS PARTS OF THE BRAIN THAT HAVE BEEN FREED FROM
INHIBITION AS A RESULT OF THE DEPRESSION OF INHIBITORY CONTROL MECHANISMS.
ALCOHOL DEPRESSES BOTH EXCITATORY AND INHIBITORY POSTSYNAPTIC POTENTIALS, IS
MORE EFFECTIVE IN INHIBITING SYNAPTIC (PARTICULARLY POLYSYNAPTIC) FUNCTION THAN
IMPULSE PROPAGATION, POTENTIATES PRESYNPTIC INHIBITION, AND HAS A VARIETY OF
EFFECTS ON TRANSMITTER SYSTEMS.
Acute alcoholic intoxication
in man is probably not associated with any great change in hepatic function.
Alcohol incr the rate at which isolated liver slices synthesize fat. It also
causes mobilization of fat from peripheral tissue. Fat thus accumulates in the
liver of normal individuals after the ingestion of relatively small amt of
alcohol. Alcohol inhibits the secretion of protein from hepatic cells, and its
prolonged use results in the accumulation of protein. The accumulation of fat
and protein may be benign at first, and the associated hepatic disorders are
reversible on abstinence. ... These processes can become irreversible and
proceed eventually to the characteristic cirrhosis seen in many alcoholics.
Malnutrition and vitamin deficiency may also contribute to the hepatic and
gastrointestinal disorders in man, particularly if alcoholic liver disease is
present.
The ability of a number of
metals and organic chemicals to induce metallothionein synthesis in primary
cultures of rat hepatocytes was tested to determine whether metallothionein
induction in vivo results from a direct effect of the agent on the liver or as a
result of an indirect, physiological response to the agent. Hepatocytes were
exposed to metals (zinc, cadmium, mercury, mangasese, lead, cobalt, nickel, and
vanadium) or org cmpd. Ethanol, urethane, L-2-oxothiazolidine-4-carboxylate, or
dexamethasonel were assayed for metallothionein by the cadmium/mercury
radioassay. Cell viability was monitored by protein synthesis activity and
cellular potassium ion concn. Increases in metallothionein concn were noted for
zinc (22 fold), mercury (6.4 fold), cadmium (4.8 fold), cobalt (2.4 fold),
nickel (22 fold), and dexamethasone (4.5 fold). However, even at max tolerated
concn, manganese, lead, vanadium, ethanol, urethane, and
L-2-oxothiazolidine-4-carboxylate did not increase metallothionein. Thus, zinc,
cadmium, mercury, cobalt, nickel, and dexamethasone induce metallothionein in
vitro and are direct inducers of metallothionein synthesis in hepatic tissue. In
contrast, manganese, lead, ethanol, urethane, and L-2-oxothiazolidine-4-
carboxylate, which did not increase the metallothionein content of hepatocytes,
apparently do so in vivo by an indirect mechanism.
Implantation of permanent
indwelling cannulas, aimed at the lateral cerebral ventricle, were made in male
Charles River mice. The effect of intracerebroventricular dilazep (25, 50 and 75
ug), and its metabolites, 1,4-bis(3-hydroxypropyl)perhydro-1,4-diazepine (15, 31
and 62 ug) and 1-(3-(3,4,5-trimethoxybenzoyloxy)propyl)perhydro-1,4-diazepine
(62 and 125 ug) on 2 g/kg ethanol induced motor incoordination was studied. Mice
were injected with ethanol 2 min after admin of the drug and evaluated for motor
coordination at 15, 30, 45, and 60 min post-ethanol. Dose related potentiation
of ethanol induced motor incoordination was noted with dilazep (p < 0.001)
and its metabolites. The motor coordination was 1, 4, 11, and 27% of normal at
15, 30, 45 and 60 min post-ethanol respectively in 50 mg/kg dilazep group (p
< 0.001). Whereas ip dilazep produced no apparent CNS effects, by the
intracerebroventricular route it caused CNS excitation including tonic clonic
seizures. Adenosine uptake inhibition, Ca2+ entry blockade or direct activation
of adenosine receptors was ruled out as the possible mechanism of seizures
because dipyridazole (50, 100 and 150 ug), verapamil (50, 75, and 100 ug) or
N6-(2-phenylisopropyl)-adenosine admin intracerebroventricularly, while
potentiating ip ethanol induced motor incoordination, did not produce seizures.
The CNS excitation was minimal with
1,4-bis(3-hydroxypropyl)perhydro-1,4-diazepine and none with
1-(3-(3,4,5-trimethoxybenzoyloxy)propyl)perhydro-1,4-diazepine. Theophylline
pretreatment (50 mg/kg) partially blocked potentiation of ethanol induced motor
incoordination by dilazep and 1,4-bis(3-hydroxypropyl)perhydro-1,4-diazepine but
not by 1-(3-(3,4,5-trimethoxybenzoyloxy)propyl)perhydro-1,4-diazepine.
Guinea pig hippocampal
pyramidal cells maintained in vitro were exposed to 50 or 100 mM ethanol.
Ethanol consistently produced a suppression of neuronal firing, causing fewer
spikes to be elicited upon stimulation by a 30 sec long depolarizing current
pulse. No differences were found between cells impaled with either potassium
chloride or potassium methyl sulfate-containing electrodes, between cells
recorded at room or elevated temperatures (30 to 32 deg C), or between slices
obtained from anesthetized or unanesthetized animals. The avg number of spikes
(from neuronal firing) decr to 65% (n= 36) of the control value in ethanol (p
< 0.0005). The ethanol effect was easily reversible, with spike frequencies
recovering to control levels after washing out the drug. Also, the ethanol
effect was blocked by treating the cell with cyclic 3',5'-adenosine
monophosphate (200 mM) or cadmium ions (300 uM). 100 mM ethanol had no effect on
the after-hyperpolarizing current.
Male Sprague Dawley rats were
fed either a control liquid diet, or an isocaloric ethanol liquid diet of the
Lieber type before being used in a study to elucidate the effects of ethanol on
immunocompetent cells. There was a significant dose-related decr in lymphokine
migration inhibitory factors (MIF) activity induced by phytohemagglutinin
related to ethanol ingestion. In concanavalin A stimulated cells an apparent
threshold effects was observed when ethanol was ingested at concn of 2 mg/kg/day
or greater, with essentially all migration inhibitory factors activity abolished
at these doses compared to 0 or 1 g/kg/day ethanol). The hypothesis of ethanol
effects on sex steroid receptor or the receptor-hormone complex translocation to
alter production of thymic stromal protein, hormone like substances was tested
by evaluating thymic stromal estrogen receptors in rats pair-fed either the
Lieber type ethanol or dextrose substituted control diet. Results (calculated
from labelled steroid binding) indicate that the correlation coefficient,
equilibrium association constant (KA) is unchanged between the two groups while
estrogen receptors incr from 51 to 54 fm/ml.
Effects of ethanol on
optokinetic, vestibular and caloric nystagmus were investigated in pigmented
rabbits to determine whether or not it affects a specific site involved in the
induction of various nystagmus. Optokinetic nystagmus was produced by rotation
of the drum housing the rabbits with vertical stripes at an angular velocity of
0.85 deg/sec. Vestibular nystagmus was induced by horizontal rotation at an
angular velocity of 30 deg/sec and caloric nystagmus by infusion of cold water
into the external meatus. Cumulative injection of ethanol into the auricular
vein to doses of 0.1, 0.2, 0.4, and 0.8 g/kg inhibited both vestibular and
caloric nystagmus in a dose-dependent manner.
The effects of ethanol on
serotonin (5-hydroxytryptamine) receptor binding in mouse brain were determined
following 7 days of ethanol ingestion. Groups of 6 male C57BL/6NCR mice were fed
either liquid diet or liquid diet in which ethanol (7% v/v) equicalorically
replaced sucrose. Control diets were adjusted daily to match avg ethanol group
amounts consumed. 5-HT(1A) receptor characteristics were measured utilizing the
agonist (3)H-8-hydroxy-2-(di-n-propylamino)tetralin and 5HT2 receptor binding
studies utilized the antagonist (3H)ketanserin. There was no change in either
5-HT(1A) or 5-HT2 receptor binding properties in any of the brain areas examined
(cortex, hippocampus, striatum, diencephalon/midbrain, and pons/medulla).
To test the hypothesis that
social ethanol consumption causes obesity by a hepatotoxic mechanism, the
relationships between alcohol intake, cigarette smoking, serum gamma-glutamyl
transpeptidase (GGT) and body build were investigated in 816 adult patients, 491
males and 325 females. A large part of the Broca index variance could be
explained by hepatic damage as reflected by the gamma-glutamyl transpeptidase
level. The higher the gamma-glutamyl transpeptidase, the more overweight were
the subjects. Hyperinsulinemia may be the pathogenetic link; insulin is the
strongest known blocker of lipolysis. Almost the total variation of obesity with
gamma-glutamyl transpeptidase, occurred in the range of gamma-glutamyl
transpeptidase up to 25 U/l, which is usually, but nevertheless erroneously,
considered to be the normal range. This effect was independent of sex and age.
Normal gamma-glutamyl transpeptidase is below 10 U/l, which is found on avg in
females aged less than 20 yr. Females tolerate less alcohol than males. Although
gamma-glutamyl transpeptidase is as high in females as in males around age 30,
males drink about three times as much ethanol. For the same Gamma-glutamyl
transpeptidase the Broca index is significantly higher in females than in males.
Gamma-glutamyl transpeptidase generally incr with age; max gamma-glutamyl
transpeptidase is reached in females in the age group 21-40 yr (due to the
change in drinking habits around 1968), declining thereafter; in males at age
50. Obesity per se is not correlated with a high gamma-glutamyl transpeptidase.
In the females there are hormonal factors influencing obesity. Although in the
females gamma-glutamyl transpeptidase decr on avg after age 40, obesity incr
(due to the decr in estrogens). After age 50 ethanol tolerance in males decr;
they reduce their alcohol consumption, and yet the gamma-glutamyl transpeptidase
remains high. Although people who smoke tend also to drink more alcohol, smokers
are significantly leaner than nonsmokers. On avg males smoke about twice as
heavily as females; this contributes to the fact that on avg males are leaner
than females despite their higher alcohol consumption. Due to lower consumption
the influence of ethanol and smoking on body build is smaller in females than in
males.
A rat model of fetal alcohol
syndrome was used by introducing pregnant Sprague-Dawley rats to a liquid diet
containing 35% ethanol derived calories (Ethanol-fed, n = 6), while a second
group was pair fed an isocaloric liquid diet without ethanol (Pair-fed, n = 6).
A third group of pregnant dams received ad libitum lab chow (Control, n = 18).
Daily maternal ethanol consumption averaged 12.7 g/kg body wt. No differences
were observed in litter size among the groups, nor were gross dysmorphological
features noted in any pups. At parturition, pups from the ethanol-fed and
pair-fed groups were crossfostered by control mothers and all groups received
lab chow. During adulthood (110 to 134 days old), male offspring were sacrificed
and hippocampal and prefrontal cortical slices were prelabeled with
(3)H-inositol. Phosphoinositide hydrolysis was determined by measuring the
accumulation of (3)H-inositol phosphates in the presence of LiCl in response to
activation of various excitatory amino acid receptors. In hippocampal slices,
ibotenate- and quisqualate-induced phosphoinositide hydrolysis was reduced in
ethanol-fed compared to pair-fed and control animals. Moreover the inhibitory
effect of N-methyl-D-aspartate on carbachol-induced phosphoinositide hydrolysis,
evident in pair-fed and control animals, was completely abolished in the
hippocampus of ethanol-fed animals. In contrast, in the prefrontal cerebral
cortex, the inhibitory effect of N-methyl-D-aspartate prevailed even in the
ethanol-fed animals.
Electrophysiological studies
were performed to determine whether or not ethanol potentiates the inhibitory
effects of gamma-aminobutyric acid on medial vestibular nucleus neurons
responding to horizontal sinusoidal rotation using alpha-chloralose anesthetized
adult male cats. The medial vestibular nucleus neurons were classified into
types I, II, III and IV neurons according to responses to horizontal rotation of
the animal placed on the turntable in directions ipsilateral and contralateral
to the recording site. Micro-osmotic application of ethanol up to 100 nA did not
affect spontaneous firing or rotation induced incr in firing of type I neurons.
However, inhibitory effects (25% inhibition at < 50 nA) of gamma-aminobutyric
acid up to 50 nA on the rotation-induced incr in firing were potentiated during
simultaneous application of ethanol up to 100 nA. The mean rotation-induced
firing rate in the 15 neurons studied was significantly (p < 0.01) decr to
85.2% of the control value during simultaneous application of ethanol and gamma-aminobutyric
acid, as compared with that by ethanol alone or gamma-aminobutyric acid alone.
This potentiated inhibition was blocked by iontophoretic application of
bicuculline (25 to 150 nA) and picrotoxin (45 to 150 nA).
Interactions:
CONCURRENT INGESTION OF
CHLORAL HYDRATE & ALCOHOL RESULTS IN GREATER CNS DEPRESSION ... CHLORAL
BETAINE, TRICLOFOS, & OTHER /RELATED/ PRODUCTS METABOLIZED TO YIELD
TRICHLOROETHANOL WILL INTERACT WITH ALCOHOL.
CONCURRENT INGESTION OF
MEPROBAMATE & ALCOHOL CAN LEAD TO ENHANCEMENT OF ... CNS DEPRESSANT EFFECTS.
EFFECTS OF AMITRIPTYLINE &
RELATED TRICYCLIC ANTIDEPRESSANTS ON ALCOHOL ARE UNPREDICTABLE.
... ALL BARBITURATES INTENSIFY
DEPRESSANT EFFECTS OF ALCOHOL.
CONCURRENT INGESTION OF
ASPIRIN & ALCOHOL MAY ENHANCE OCCULT BLOOD LOSS & GASTRIC DAMAGE INDUCED
BY ASPIRIN. ... MOST FORMS OF SALICYLATES MAY INTERACT WITH ALCOHOL ... .
... PT TREATED WITH ORAL
HYPOGLYCEMIC AGENTS MAY EXPERIENCE UNPLEASANT SYMPTOMS SIMILAR TO THOSE
EXPERIENCED BY PT WHO TAKE DISULFIRAM AFTER INGESTION OF ALCOHOL. SIMILAR
INTERACTIONS CAN OCCUR WITH METRONIDAZOLE OR CEPHALOSPORINS. ... THE
HYPOGLYCEMIC EFFECT OF INSULIN MAY ALSO BE MARKEDLY INCR. ALCOHOL CAN INTERFERE
WITH THE THERAPEUTIC ACTIONS OF A WIDE VARIETY OF DRUGS BY ALTERING THEIR
METABOLISM. ... ACUTE INGESTION OF ETHANOL REDUCES THE CLEARANCE OF PHENYTOIN
BECAUSE BOTH DRUGS COMPETE FOR THE SAME HEPATIC MICROSOMAL OXIDASE SYSTEM.
ALCOHOL MAY ALSO INTERFERE
WITH THERAPEUTIC ACTIONS OF ... COUMARIN TYPE OF ANTICOAGULANT ... .
16 HEALTHY VOLUNTEERS TOOK
PART IN A CROSSOVER STUDY EXAMINING THE EFFECT OF ETHYL ALCOHOL ON THE RATE OF
SULFAMETHAZINE ACETYLATION. APPARENT HALF-LIFE OF DRUG DECR BY ABOUT 20% AFTER
ETHANOL AND AMT OF DRUG ACETYLATED, MEASURED IN BLOOD & URINE, INCREASED.
IN MICE & RATS,
METHAQUALONE DELAYED DISAPPEARANCE OF ETHANOL IN BLOOD & BRAIN OVER A PERIOD
OF 50 TO 200 MIN AFTER A LOADING DOSE OF 2.0 G/KG, IP OF ETHANOL. METHAQUALONE @
140 AND 200 MG/KG INCR ETHANOL TOXICITY BY 11% AND 28%, RESPECTIVELY. CO-ADMIN
OF ETHANOL USING 6.0, 7.0, AND 8.0 G/KG ALSO REDUCED THE LD50 OF METHAQUALONE BY
19, 24, AND 40%, RESPECTIVELY. CHRONIC ETHANOL ADMIN DECR METHAQUALONE TOXICITY.
COADMIN OF
ALPHA-1-ACETYLMETHADOL @ 18 OR 36 MG/KG POTENTIATED ETHANOL TOXICITY; LD50 DUE
TO ETHANOL WAS LOWERED BY 21 & 36%, RESPECTIVELY. ETHANOL (0.5 & 1 G/KG)
DECR ALPHA-1-ACETYLMETHADOL TOXICITY; LD50 WAS INCR TO 76 AND 64 MG/KG,
RESPECTIVELY, COMPARED WITH 56 MG/KG FOR ALPHA-1-ACETYLMETHADOL ALONE. AT 4 G/KG
ETHANOL, LD50 WAS DECR TO 43.9 MG/KG, SHOWING POTENTIATION OF INTERACTION
TOXICITY.
DIABETIC PT TREATED WITH
PHENFORMIN SHOULD AVOID INGESTION OF ALCOHOLIC BEVERAGES BECAUSE CONCURRENT USE
MAY CAUSE HYPOGLYCEMIC REACTIONS OR LEAD TO LIFE THREATENING LACTIC ACIDOSIS
WITH SHOCK.
In hamsters given ethanol in
drinking water and also given the known pancreatic carcinogen
N-nitrosobis(2-oxopropyl)amine (20 mg/kg, sc) no neoplastic lesions were
observed at the end of the expt, whereas 11 of 14 hamsters given the carcinogen
alone showed neoplastic lesions. Lipase activity was reduced in hamsters given
the carcinogen but was normal in the ethanol + carcinogen treated animals.
A serious, relatively
unrecognized occupational health problem involves the interaction of ethyl
alcohol and chem agents used in industry. Workers who drink alcohol and are
exposed to certain chem agents may experience adverse health effects such as
nausea, dizziness, headache and liver damage. The synergistic interactions of
ethanol with cmpd such as the thiurams, amides, oximes, halogenated hydrocarbons
and metals were reviewed.
The influence of several
neotropic drugs (piracetam, pyritinol, meclofenoxat, methylglucamine orotate (MGO)
and dihydroergotoxine (DHET)) on both the ethanol preference and the enhanced
seizure susceptibility after a single dose of ethanol was studied. Piracetam,
MGO and DHET reduce the ethanol drinking in ethanol preferring mice. The
enhanced seizure susceptibility after a single dose of ethanol was abolished by
piracetam and MGO.
The ascending noradrenergic
pathways from the locus coeruleus were lesioned bilaterally in 10 rats by
intracerebral 6-hydroxydopamine injections. Ten rats were sham operated. All
animals were subjected to a 4 day ethanol intoxication period using intragastric
intubation. Intoxication and withdrawal assessments were performed blindly. The
6-hydroxydopamine lesions did not appear to affect tolerance to ethanol. During
withdrawal, however, lesioned animals showed minor, but statistically
significant changes in scores of certain non-convulsive withdrawal signs, but
incidence and intensity of spontaneous and audiogenic convulsive seizures were
not different between the groups.
A fatal case of multiple drug
abuse in a 36 year old veterinarian involving injection of xylazine and
ingestion of alcohol and clorazepate is presented. Quantitative analysis of
xylazine was by gas liquid chromatography with a nitrogen detector. Xylazine
concentrations (mg/l or mg/kg) were: blood, 0.2; brain, 0.4; kidney, 0.6; liver,
0.9; lung, 1.1; omentum adipose 0.05; and urine, 7.0. Blood ethanol and
nordiazepam concentrations were 380 mg/dl and 2.5 mg/l, respectively.
A pharmacokinetic study was
conducted to determine the effectiveness of lower doses of ethanol in the
treatment of ethylene glycol (EG) poisoning. Four dogs were maintained at serum
ethanol concentrations of 0, 35 and 140 mg/dl prior to EG (iv, 2 ml/kg)
administration. The serum EG concentration-time data showed that the 35 mg/dl
ethanol level provided as effective an inhibition of EG metabolism as did the
140 mg/dl level. The average urinary excretion rate of oxalic aid post EG
administration was reduced to control levels by ethanol. The 35 mg/dl serum
ethanol level reduced the total body clearance of EG from 93.9 to 50.0 ml/hr/kg
and increased the effective half-life from 5.78 to 11.4 hr. Clinical testing was
accomplished by giving the dogs 12 ml EG/kg body weight orally. One hour later,
the dogs were either not treated or treated with a sodium bicarbonate-ethanol
solution to obtain a serum ethanol concn of 50 mg/dl. The clinical test
performed in the ethanol-treated dogs showed little change from normal limits.
Urine calcium oxalate crystals were seldom found. The dogs given EG (12 ml/kg)
but not treated with ethanol were in a coma at 13 hr and showed severe metabolic
acidosis, dehydration, mild hepatocellular disease, and acute renal damage.
Urine calcium oxalate crystals were found in high numbers. The rapid death
associated with EG poisoning appeared to be due to metabolic acidosis in
combination with dehydration.
Because alcoholism has adverse
effects on Zn nutrition and many pregnant women consume less than the
recommended dietary allowances of Zn, it was postulated that Zn deficiency acts
as a co-teratogen with alcohol in the fetal alcohol syndrome. The effects of
alcohol on progeny of pregnant mice fed a Zn deficient diet were compared to
those fed a diet containing adequate Zn. Pregnant CBA mice (n= 66) were fed the
Lieber-DeCarli liquid diet with 0, 15, or 20% ethanol derived calories
containing 0.3 (low) or 8.5 (high) mug Zn/ml. Dams were sacrificed on day 18 of
gestation. Resorptions, malformations, and individual fetal weights were
recorded. Analysis of fetuses included assays for Zn, assessment of soft tissue
malformations, and alizarin red staining for skeletal malformations. Fetal
weights were lower in the groups fed the Zn-deficient diet for each
concentration of alcohol (p < 0.005). The groups fed the combination of low
Zn plus alcohol had 37-52% resorptions, while the animals on the Zn deficient
diet without alcohol or the high Zn diet with alcohol diet had 0-2% resorptions.
Skeletal malformations were related to alcohol concn but not Zn intake, while
external malformations were higher in those maintained on the low Zn ethanol
diet. These results suggest that Zn deficiency potentiated the teratogenic
effects of alcohol and that nutritional intervention for alcoholic women during
pregnancy might reduce the incidence or severity of fetal alcohol syndrome.
The interaction of ethanol
with drugs and xenobiotics is complex because ethanol can affect any of the
following steps; absorption, plasma protein binding, hepatic blood flow,
distribution, hepatic uptake of drugs, and phase I and II hepatic metabolism.
The ingestion of ethanol can lead to malabsorption of drugs. High concn of
ethanol in conjunction with aspirin causes gastric mucosal damage. The principal
effect of acute ethanol ingestion on drug metabolism is inhibition of microsomal
drug metabolism. The synergistic effects of ethanol on central nervous system
depressants can be explained by this mechanism. In contrast, chronic ethanol
consumption increases mixed function oxidation and drug metabolism. The cross
tolerance between ethanol and sedatives in chronic alcoholics may be due to this
effect of alcohol. In addition, increased production of hepatotoxic products
from certain drugs and xenobiotics and an increased activation of procarcinogens
to carcinogens can result from this microsomal induction. The increased
susceptibility to hepatotoxins and the enhanced carcinogenesis in the alcoholic
may be explained by this fact. Other effects of the interaction between drugs
and alcohol are the result of changes in organ susceptibility, best demonstrated
for the central nervous system. Subsequently, the presence of liver disease has
a great effect upon drug metabolism in alcoholics.
Pharmacokinetic interactions
of ethanol with other drugs including its effects upon drug metabolite
disposition, are reviewed in terms of clearance concepts. This approach is
particularly useful in understanding the mechanisms of ethanol drug interactions
(ie in separating the effects of ethanol upon drug clearance, volume of
distribution and plasma protein binding.) The application of clearance concepts
provides the basis for understanding the qualitative differences in ethanol
interactions with low and high hepatic extraction ratio drugs. The effects of
short and long term ethanol consumption upon different types of drug metabolism
(oxidative, acetylation and glucuronidation) have been considered. Lomg term
ethanol consumption may increase the clearance of a drug by induction of
oxidative metabolism whereas short term consumption may decrease the clearance
of such a drug. Clearance by N-acetylation appears to be increased in the
presence of ethanol, while clearance by conjugation to glucuronic acid is
decreased for some drugs by single dose consumption of ethanol.
Hepatocytes isolated from male
Sprague-Dawley rats (Harlan, 200-275 g) were exposed to halogenated and non
halogenated hydrocarbons. Leakage of cellular enzymes and inhibition of
respiration were monitored as indicators of toxicity. Cell suspensions contained
2-3X10+6 cells/ml and were viable for 6 hr as indicated by a < 10% increment
in the fractional release of aspartate aminotransferase (AST) activity. The
hydrocarbons were added to the cell suspension as 20% solutions in ethanol. Only
3% of the AST activity was found in the medium at the beginning of the
experiment, and there was no increase with time in cells treated with ethanol
(n= 4). The relationship of the effects of cellular respiration to alteration in
mitochondrial function was studied using dinitrophenol (DNP), an uncoupler of
oxidative phosphorylation, and succinate, an NADH independent mitochondrial
substrate. Ethanol caused a decrease in the DNP stimulated oxygen consumption
(n= 5-8), but had essentially no effect on the succinate stimulated oxygen
consumption. All parameters of mitochondrial function returned to control levels
within one hr.
The effects of a combined high
glucose diet and ethanol on chronic hexachlorobenzene (HCB) intoxication were
examined using male Wistar rats. Treatments were: (1) glucose diet (63% glucose)
(n= 10), (2) glucose diet plus 17.5 mmol HCB/kg food (n= 20), (3) glucose diet
plus HCB plus 10% ethanol in the drinking water at an average of 0.104 mol
ethanol/kg body weight daily (n= 20), (4) glucose diet plus ethanol (n= 10), (5)
standard (control) diet (63% starch) (n= 30), and (6) standard diet plus HCB (n=
30). The treatment period lasted 60 days. HCB treatment produced clonic
convulsions, tremors, and hyperexcitability with symptoms appearing earlier and
more intensely in rats fed the standard diet. Ethanol itself affected only serum
enzymes, increasing them significantly. The glucose diet and ethanol exerted
contrasting effects so that the combination of glucose diet plus HCB plus
ethanol produced similar results to those obtained with the standard diet plus
HCB.
Drinking habits of rotogravure
printers exposed to toluene were not found to influence performances on
psychological examinations. Drinking habits were considered in grouping the
workers. The test battery consisted of standardized tests for verbal and visual
cognition and memory, perceptual motor speed, and psychomotor abilities. Within
the rotogravure group, workers were divided into subgroups with (A) high toluene
exposure (greater than 120 ppm) with heavy drinking, (B) high exposure with
moderate drinking, (C) low exposure with heavy drinking, and (D) low exposure
without heavy drinking. Mean test performances indicated that drinking habits
did not explain the impairment of visual cognitive abilities. Heavy drinkers
with high toluene exposure had intact performances.
The effects of a selective
5-hydroxytryptophan receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin on
ethanol preference was studied in 34 male Wistar strain rats. The rats had
access to a 6% (vol/vol) ethanol solution and water during baseline and
treatment periods. Based on the baseline recordings, 2 groups of rats were
formed: a high preference group (ethanol intake >50% of total fluid intake)
and a low preference group (ethanol intake <30%). Both groups were treated sc
with 0.125 mg/kg 8-hydroxy-2-(di-n-propylamino) tetralin twice daily for 3 days.
The treatment caused a significant reduction of ethanol consumption in the high
preference group, but no change in the low preference group.
Male and female long sleep and
short sleep mice were pretreated with ethanol at varying doses (0 to 4 g/kg) 7.5
min prior to challenge with an ED80 dose of nicotine (long sleep: 4.25 mg/kg;
short sleep: 6.25 mg/kg). Long sleep mice were more sensitive to the
anticonvulsant effects of ethanol than were short sleep mice. To assess the
effect of ethanol on the nicotine induced behavioral desensitization to nicotine
observed previously in these mice, animals were pretreated with saline,
nonanticonvulsant doses of ethanol (0.25 g/kg, 0.75 /kg or 1.5 g/kg), a
subseizure producing dose of nicotine (2.0 mg/kg) or a combination of these two
drugs 15 or 30 min prior to nicotine challenge. Ethanol enhanced the nicotine
induced behavioral desensitization in both mouse lines; however, this effect was
seen at lower ethanol doses and was more pronounced in long sleep mice. Ethanol
pretreatment did not affect brain nicotine concn in either long sleep or short
sleep mice.
The effect of acute (2.0 g/kg,
intragastrically) and chronic (8.0 to 11.0 g/kg/day for 10 days,
intragastrically) ethanol exposure on beta-endorphin in plasma, hypothalamus and
pituitary, and on catecholamines in hypothalamus and plasma, and on
corticosterone in plasma were examined in male Sprague Dawley rats. Plasma
beta-endorphin, norepinephrine and corticosterone levels were significantly incr
and dopamine was unchanged in acute and chronic ethanol treated rats. Compared
to controls, plasma epinephrine levels were incr in acute ethanol treated rats
but no significant change was observed in chronic ethanol treated rats. Plasma
dopamine was significantly decr following chronic ethanol treatment while no
significant change was observed after acute treatment. In the hypothalamus,
beta-endorphin and dopamine contents were incr and norepinephrine levels were
decr in response to ethanol exposure. Beta-endorphin levels were decr
significantly in the anterior pituitary and the neurointermediate lobe of the
pituitary in ethanol treated animals except in the neurointermediate lobe of the
chronic ethanol treated animals.
Male albino Wistar rats
trained to alternately shuttle between nose poke and lever operanda for
rewarding stimulation to the medial forebrain bundle, were tested following
intragastric intubations of ethanol (18%, 1.35 g/kg), the imidazobenzodiazepine,
Ro 15-4513 (3 mg/kg in 18% ethanol), or vehicle. The duration of the alternation
between operanda was significantly faster when the rats were intubated with
ethanol. Ro 15-4513 treatment reversed ethanol enhanced effects on reinforced
responses (p<0.05).
One group (n= 21) of male
Sprague-Dawley rats (310 to 360 g) were given gastric intubations of ethanol
soln (10% w/v), while others (controls, n= 16) received isocaloric
maltose-dextrin soln (17.5% w/v). Rats were given their soln every 8 hr for 24,
48, or 96 hr, alone or in combination with prazosin (1.0 mg/kg, every 8 hr, per
os). The initial dose of ethanol was 5 g/kg, after which the criteria for
subsequent doses were based on sign of intoxication displayed by individual
animals just prior to the dose being given. Adrenal glands of rats receiving
ethanol were larger (72.0 mg/pair after 48 hr) than those from control animal
(57.4 mg); prazosin did not affect this (74.1 mg). In contrast, concurrent
treatment with prazosin enhanced the loss of medullar catecholamines (by 60% at
24 hr) and noradrenaline (by 24% at 2 days) from hearts of rats given ethanol,
while it had no such effects in controls. Excreted quantities of catecholamines
were markedly increased in rats given ethanol and prazosin. Hearts of animals
given the combined treatment of ethanol and prazosin showed cardiomegaly at 24
hr, when there was an incr of about 20 in proportional heart wt, an incr that
persisted through the remaining 3 days of the study. At 48 hr, hearts of animals
give prazosin and ethanol were heavier than those given ethanol alone. A
significant correlation between catecholamine excretion and development of
cardiac hypertrophy was identified.
Preincubation with 2 M ethanol
inhibited L-alanine uptake, proton efflux and fermentation rates of exponential
phase cultures of Auxotrophic strain Saccharomyces cerevisiae, KD115. Ethanol's
inhibitory effect varied in yeast cells enriched with different fatty acyl
residues. Ethanol's effect gradually decreased with incr unsaturation index. It
was observed that cells enriched with polyunsaturated fatty acids acquired
greater tolerance to ethanol as compared to monounsaturated fatty acids. By
varying the degree of unsaturation of supplemented fatty acids a sequential
insertion of double bonds in yeast membrane lipid was achieved. Incr concn of
ethanol inhibited the efflux of H+ in palmitoleate and oleate enriched cells,
but caused negligible effects of H+ efflux in linoleate and linolenate enriched
cells. Percentage inhibition by ethanol of fermentative activity was reduced
with incr unsaturation. As compared to palmitoleate, oleate and linoleate the
inhibitory effect of ethanol on the fermentation rate of linolenate supplemented
cells was the least.
Male rats (n= 40) were given a
single ip injection of 30 mg azaserine/kg body wt at 19 days of age. The animals
were fed a semipurified diet high in unsaturated fat (HF, 25% corn oil) either
separately (n= 40) or in combination with ethanol (n= 40), which was provided in
drinking water from day 25 onward at a concn of 10% (w/v). A separate group
(control) was maintained on a diet low in unsaturated fat (LF, 5% corn oil).
Rats were killed after 15 mo, and their pancreas, liver and kidneys were
weighed. Dietary fat was found to enhance pancreatic carcinogenesis in rats.
Ethanol slightly enhanced the multiplicity but not the incidence of malignant
tumors (79 vs 86%). With ethanol, a nonsignificant incr in the number of
atypical acinar cell nodules (AACN) with a diameter > mm was seen. In the
high unsaturated fat + ethanol group the number of adenomas was lower than in
the high unsaturated fat group (156 vs 176), which was accompanied by
statistically nonsignificant, increase of malignant tumors (71 vs 57).
Male hamsters were injected sc
with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body wt at 6 and 7 wk of age.
The animals were fed a semi purified diet high in unsaturated fat (HF, 25% corn
oil) either separately (n= 40) or in combination with ethanol (n= 40), which was
provided in drinking water at a concn of 10% (w/v). Ethanol was introduced at 5%
after the second carcinogen treatment, and gradually incr to 10% after 6 wk. A
separate group (control) was maintained on a diet low in unsaturated fat (LF, 5%
corn oil). Hamsters were killed 12 mo after the last BOP injection, and their
pancreas, liver an kidneys were weighed. Dietary fat was found to enhance
pancreatic carcinogenesis in hamsters. Ethanol did not influence the enhancing
effect of high unsaturated fat on the development of ductular carcinomas in
hamster pancreas. The number of tumor bearing hamsters was 25 for high
unsaturated fat + ethanol and 29 for high unsaturated fat, while total
adenocarcinomas were 35 and 37, respectively.
In urethane anesthetized
albino Wistar rats, intracerebroventricular (ICV) microinjections of 1.61x10-6
and 7.82x10-4 mol of ethanol induced cardiac arrhythmias in 65.5% of the
experiments. Cardiac disorders caused by ethanol (2.60x10-5 and 2.08x10-4 mol)
were prevented by previous ICV admin of atropine (1.43x10-7 mol) and propranolol
(3.86x10-7 mol). When toliprolol microinjections (3.38x 10-7 and 6.76x10-7) were
associated with ethanol (1.04x10-4 and 4.69x10-4 mol) arrhythmias were evident
in 4/6 expt, compared to toliprolol eliciting arrhythmia in 2/6 expt. IV
injection of ethanol (1.46x10-5 and 6.26x10-3 mol/animal) induced cardiac
arrhythmias in 85% (51 out of 60) of the expt. IV admin of atropine, toliprolol,
propranolol, phentolamine, pheniramine, cimetidine, or aprotinin 20 min prior to
ethanol failed to affect the arrhythmogenic properties of ethanol. Ethanol
(3.26x10-4 mol/kg) had no effect on the cardiac arrhythmias induced by iv
adrenaline (1.09x10-7 mol/kg. Ethanol also failed to antagonize the centrogenic
arrhythmias elicited by ICV sodium L-glutamate.
6o o [Pampulha ME, Loureiro V;
Biotechnol Lett 11 (4): 269-74 (1989)] Acetic acid inhibited fermentation in a
respiratory deficient mutant of Saccharomyces cerevisiae (IGC 3507-111) in an
exponential way. The undissociated form of the acid probably was the toxic
agent. Ethanol potentiated this effect in a synergistic exponential way.
Calculated values for inhibition constants of undissociated acetic acid
(l/moles) in the presence of three concn of ethanol (0, 5, and 10 % vol/vol) at
three pH values were: 34.0, 44.0, and 64.0, respectively at pH 3.5; 48.0 59.0,
and 85.0, respectively at pH 4.5; and 65.0, 84.0, and 101.2, respectively at pH
5.5.
... Ethanol, isopropanol, n-butanol,
sec-butanol, and tert-butanol ... exert a ... potentiating effect on the acute
inhalation toxicity of carbon tetrachloride. ... Interaction between isopropanol
& carbon tetrachloride was documented in an industrial accident ... where
workers exposed to both agents exhibited hepatotoxicity. With ethanol the
potentiation seems to be due to the presence of the unmetabolized alcohol;
however, with isopropanol the effect seems to be caused by the presence of both
unmetabolized alcohol and acetone. The results obtained with n-butanol resemble
those of ethanol, whereas with 2-butanol they resemble those of isopropanol ...
ADDING 1 G/L OF PROPAN-1-OL,
PROPAN-2-OL, BUTAN-1-OL, BUTAN-2-OL, ISOBUTANOL TO 40% ETHANOL IN ORANGE JUICE
LOWERED AND DELAYED BLOOD ETHANOL MAX IN TEN, 20-30 YR OLD MEN WHO DRANK 3.75
ML/KG OF SYNTHETIC BEVERAGE.
Adverse interactions with
alcohol: interacting drug: acetaminophen; adverse effect: incr acute
hepatotoxicity /From table/
Adverse interactions with
alcohol: interacting drug: anesthetics; adverse effect: decr effectiveness for
induction of anesthesia /From table/
Adverse interactions with
alcohol: interacting drug: antihistamines; adverse effect: incr CNS depression
with acute intoxication /From table/
Adverse interactions with
alcohol: interacting drug: benzodiazepines; adverse effect: incr CNS depression
/From table/
Adverse interactions with
alcohol: interacting drug: bromocriptine (parlodel); adverse effect: nausea,
abdominal pain /From table/
Adverse interactions with
alcohol: interacting drug: chloramphenicol (Chloromycetin); adverse effect:
minor antabuselike symptoms /From table/
Adverse interactions with
alcohol: interacting drug: cycloserine (Seromycin); adverse effect: incr
convulsions chronic abuse /From table/
Adverse interactions with
alcohol: interacting drug: disulfiram (Antabuse); adverse effect: abdominal
cramps, flushing, vomiting, psychotic episodes, confusion /From table/
Adverse interactions with
alcohol: interacting drug: isoniazid (INH); adverse effect: incr incidence of
hepatitis, decr isoniazid effect in some patients with chronic alcohol abuse
/From table/
Adverse interactions with
alcohol: interacting drug: methisazone (Marboran); adverse effect: incr
methisazone toxicity /From table/
Adverse interactions with
alcohol: interacting drug: metronidazole (Flagyl); adverse effect: mild antabuse
like symptoms /From table/
Adverse interactions with
alcohol: interacting drug: narcotics; adverse effect: incr CNS depression with
acute intoxication /From table/
Adverse interactions with
alcohol: interacting drug: phenothiazines; adverse effect: incr CNS depression
/From table/
Adverse interactions with
alcohol: interacting drug: phenytoin (Dilantin); adverse effect: decr
anticonvulsant effect with chronic alcohol abuse /From table/
Adverse interactions with
alcohol: interacting drug: propranolol (Inderal); adverse effect: masks
tachycardia and tremor of alcoholic hypoglycemia /From table/
Adverse interactions with
alcohol: interacting drug: quinacrine (Atabrine); adverse effect: minor antabuse
like symptoms /From table/
Ethanol enhances the effects
of coumarin anticoagulants ... insulin, monoamine oxidase inhibitors ...
Disulfiram like intolerance to ethanol may occur from sulfonylureas,
thiocarbamates, metronidazole, tolazoline, furazolidone, chloramphenicol, and
quinacrine.
In a group of patients
receiving aminosalicyclic acid for hyperlipidemia, the three pt who ingested
ethanol developed a diminished hypolipidemic response.
Chronic ethanol abuse can
produce induction of hepatic microsomal enzymes resulting in enhanced antipyrine
metabolism. ... It is proposed that the activity of alcohol dehydrogenase can be
enhanced by incr ascorbic acid saturation. In healthy volunteers, the clearance
of ethanol was slightly enhanced by ascorbic acid admin (1 g/day for 2 wk).
It is proposed that prolonged
intake of large amt of ethanol may enhace the metabolism of chloroform to
hepatoxic metabolites. ... Cimetidine probably inhibits hepatic ethanol
metabolism and/or incr the gastrointestinal absorption of ethanol.
A case has been reported in
which ethanol may have contributed to the psychotoxic reaction in an ethionamide
treated patient.
One would expect additive CNS
depression with combined use of ethanol and glutethimide. Pharmacokinetic
interaction has also been suggested. ... Acute intoxication with ethanol appears
to inhibit meprobamate metabolism while chronic ethanol ingestion appears to
induce hepatic microsomal enzymes resulting in enhanced meprobamate metabolism.
... Ethanol and metoclopramide may exhibit additive sedative effects.
Ethanol produces vasodilation,
which may enhance the orthostatic hypotension of guanethidine.
It has been proposed that
ethanol may enhance the possibility of methotrexate induced hepatotoxicity.
Hypotension reportedly may
occur following the combined use of ethanol and nitroglycerin. This is
presumably due to the vasodilation which both agents may produce.
Ingestion of alcohol
reportedly enhances the degradation of "all penicillins" but no
supporting clinical evidence is given.
Ethanol appears to enhance the
acetylation of procainamide in the liver.
A disulfiram like reaction
reportedly may occur following ethanol ingestion in pt receiving procarbazine.
Additive CNS depression may also occur.
Sulfonamides reportedly incr
the adverse effects of ethanol and further impair driving ability. However, no
supporting clinical data are given so that the clinical significance cannot be
assessed.
A small amt of admin
tetrachloroethylene is absorbed from the gastrointestinal tract, resulting in
CNS depression. This effect may be additive with that of alcohol.
Chronic ingestion of large amt
of ethanol may result in induction of hepatic microsomal enzymes. Since
doxycycline is metabolized by the liver, its metabolism may be enhanced in
alcoholic pt.
Industrial exposure to
trichloroethylene has been associated with ethanol intolerance ...
CD 1 mice were treated ip on
day 10 of gestation with 4, 6, or 7 g/kg ethanol. Ethanol rapidly crossed the
placenta and appeared in the embryo 5 min after treatment. Acetaldehyde was
detectable in maternal blood following all treatments and in maternal liver and
embryos following treatment with 7 g/kg ethanol. Coadministration of 100 mg/kg
4-methylpyrazole, an alcohol dehydrogenase inhibitor, with 4 or 6 g/kg ethanol
on day 10 of gestation significantly reduced the rate of ethanol elimination in
all tissues examined. These data suggest that both ethanol and acetaldehyde are
accessible to the embryo during a critical period of development.
IP ADMIN OF ETHANOL (0.7-1.8
MG/G/DAY FOR 7 DAYS) TO MICE DECR LEVEL OF HEPATIC MICROSOMAL CYTOCHROME P450,
ARYLHYDROCARBON HYDROXYLASE, & PROTEIN. ORAL ETHANOL (10% IN DRINKING WATER,
2-8 WK) DECR MICROSOMAL PROTEIN CONTENT, THEN INCR IT; P450 INCR,
ARYLHYDROCARBON HYDROXYLASE DECR. IN MICE PRETREATED BOTH ORALLY & IP WITH
ETHANOL THE BINDING OF BENZO(A)PYRENE (B(A)P) TO DNA INCR. MORE TUMORS DEVELOPED
IN PRETREATED MICE GIVEN B(A)P THAN IN CONTROLS GIVEN ONLY B(A)P. PRETREATED
MICE HAD MUSCLE TUMORS, CONTROLS HAD MAMMARY TUMORS.
Ethanol, 25 to 50 mM added to
cultured pineal glands in vitro, enhanced isoproterenol induced stimulation of
cyclic AMP and melatonin production. Cells were obtained from rats decapitated
during the light phase of a 14 hour light/10 hour dark cycle. The action of
ethanol was observed only at doses of isoproterenol that produced a submaximal
effect, and ethanol alone had no effect on cyclic AMP or melatonin release. The
effects of ethanol on pineal cyclic AMP and melatonin release were reversible
after a 15 min preincubation but not after a 2 hour preincubation.
THE METABOLISM IN VIVO OF
ISOBUTANOL IN RATS LIVER, EVEN IN LOW CONCN, WAS MARKEDLY INHIBITED BY
SIMULTANEOUS OXIDATION OF ETHANOL.
9 HR AFTER TERMINATION OF
DRINKING 3.75 ML OF BEVERAGE CONTAINING 40% ETHANOL IN ORANGE JUICE @ 1.2 G
ETHANOL/KG PLUS 1 G/L ISOBUTANOL, THE CONGENER ALC OR THEIR METABOLITES CAUSED
INCR OF ERROR FIGURES & SUBJECTIVE HANGOVER SYMPTOMS.
ETHANOL (LESS THAN 0.5 MMOLE),
TERT-BUTANOL, & N-PROPANOL INHIBITED N-NITROSODIMETHYLAMINE METABOLISM IN
ISOLATED PERFUSED RAT LIVER.
The effects of prolonged
infusions of ethanol on endothelium dependent vasorelaxation induced by
acetylcholine and adenosine triphosphate (ATP) and on endothelium independent
relaxation induced by papaverine were studied and compared in isolated perfused
male Sprague Dawley rat mesenteric artery preparations. Infusion of ethanol over
60 min at concn of 1.6, 4.7, 6.3, and 7.9 mg/ml caused concn related inhibition
of norepinephrine-induced vasoconstriction. In preparations infused with 6.3 and
7.9 mg/ml, this effect reached a maximum after 10-20 min but had vanished by the
end of the infusion; 1 hr after the end of the infusion, the effects of
norepinephrine were potentiated by 71% and 108%, respectively. Acetylcholine
induced vasorelaxation (EC50 3.0 ng/ml in controls) was significantly reduced
after 6.3 mg/ml ethanol infusion and totally abolished after 7.9 mg/ml ethanol
infusion. ATP induced vasorelaxation (EC50 180 ng/ml in controls) was also
abolished after 7.9 mg/ml of ethanol infusion. By contrast, the vasorelaxant
effects of papaverine were not affected by 7.9 mg/ml ethanol infusion.
Light-microscopic examination revealed that the endothelial cells were present
in ethanol treated and in control mesenteric arterial beds.
Effects of silybin
dihemisuccinate on the ethanol metabolizing systems of the rat liver were
investigated using male Wistar rats. Fifteen min after intoxication with ethanol
(2.0 g, 3.5 g or 5.0 g/kg; ip), the animals were treated with 20 mg, 30 mg or 50
mg/kg of silybin dihemisuccinate (iv via femoral vein), and blood ethanol
concentrations were determined at hourly intervals after ethanol intoxication.
Results showed that silybin dihemisuccinate increased blood ethanol only when
intoxication was produced by doses of 3.5 g and 5.0 g/kg but not by 2 g/kg of
ethanol. This effect is ascribed to an inhibition of the microsomal ethanol
oxidizing system. Activities of alcohol dehydrogenase, catalase and NADPH-dependent
cytochrome c reductase were not affected by silybin dihemisuccinate.
The relationship between
lifetime alcohol (ethanol) consumption and respiratory symptoms in 195 subjects
(including 111 alcoholics) and FEV1 pulmonary function level in 165 subjects
(including 91 alcoholics) was examined. The mean ages for subjects from the
Brockton VA Medical Center were 44.3 yr for pt (in an alcohol treatment program)
and 41.0 yr for employees. Median duration of alcohol consumption was 21 yr, and
the median alcohol consumption was 1527 kg-yr for the pt and was 72 kg-yr for
employees. After adjustment for age and cigarette smoking status, using multiple
logistic regression, lifetime alcohol consumption was a significant predictor of
chronic cough and chronic phlegm, but not of any wheeze or persistent wheeze.
Multiple linear regression analysis indicated that lifetime alcohol consumption
was also a predictor of lower levels of FEV1 in a model that included age,
pack-yr of cigarette smoking, and an interaction between alcohol consumption and
pack-yr. For subjects with both heavy alcohol consumption and smoking, the level
of pulmonary function was higher than expected compared to the effect of smoking
alone.
The present study was
undertaken to isolate and identify specific anatomical structures in the
limbic-midbrain, limbic-forebrain which mediate changes in the ingestion of
alcohol induced by tetrahydropapaveroline. In adult male Sprague Dawley rats, a
23 gauge guide tube was implanted stereotaxically either unilaterally or
bilaterally in cerebral regions extending from coronal planes AP 1.0 to 10.0.
Following recovery, each animal was tested by a standard screen for its
self-selection of water versus an alcohol solution offered in 10 concn increased
on each of 10 days from 3 to 30%. Tetrahydropapaveroline was dissolved in an
artificial CSF vehicle containing Na2S2O5 or ascorbate and then microinjected in
a volume of 1.5 to 2.0 ul at a depth 1.0 to 1.5 mm beneath the tip of the guide.
After a set of 5 microinjections of tetrahydropapaveroline in a dose of 25, 50
or 250 ng was given over 3 days, the same lO day alcohol preference sequence was
repeated. In nearly all rats, the microinjection series was repeated at either
one or two depths 1.0 to 1.5 mm ventral to the first, after which the same
alcohol test was repeated. The results showed that tetrahydropapaveroline
induces or sustains significant incr in alcohol intake when the adduct was
injected at 16 sites within caudal AP planes 1.0 to 5.0. Structures sensitive to
tetrahydropapaveroline included the substantial nigra, reticular formation,
medial lemniscus, zone incerta and medial forebrain bundle. When injected at 21
sites located more rostrally within AP planes 6.5 to 10.0,
tetrahydropapaveroline also evoked significant increments in alcohol intake of a
similar magnitude. The reactive loci included the N. accumbens, olfactory
tubercle, lateral septum, preoptic area, stria terminalis, medial forebrain
bundle and rostral hippocampus. In terms of the efficacy of the dose of
tetrahydropapaveroline microinjected, 25, 50 and 250 ng induced alcohol
self-selection in 81%, 5% and 14% of the sites, respectively. Repeated
microinjections following identical procedures of two control solutions (0.9%
saline or Na2S2O5) at 46 homologous sites within corresponding coronal planes
from AP 1.5 to 10.0 produced no significant alterations in g/kg or proportional
intakes of alcohol. For the rats, the mean intakes of maximally preferred concn
of alcohol in g/kg were 3.83 after caudal injection of tetrahydropapaveroline
(n= 15), 4.36 after rostral injection of tetrahydropapaveroline (n= 20), 0.53
after Na2S2O5 control (n= 18) , and 0.91 after saline control injection (n= 23).
Composite anatomical maps of the tetrahydropapaveroline reactive sites revealed
their integral overlap with dopaminergic pathways which originate in the ventral
tegmentum and substantia nigra and project rostrally to structures within the
limbic forebrain.
Sensitivity to bleomycin
induced chromosome damage in 75 pt (53 men and 22 women) with previously
untreated upper aerodigestive tract malignancies was compared with that in 62
healthy control subjects. Of the pt, 22 (29.3%) had carcinoma of the larynx, 20
(38.7%) had oral cavity lesions, and 23 (30.7%) had pharyngeal malignant tumors.
Data on alcohol use were derived from a questionnaire. 45 pt and 13 controls
were sensitive to bleomycin induced mutagenesis (age breaks/cell > 0.8).
There were site specific differences in the elevated risks associated with
ethanol consumption. The odds ratios for alcohol use were 6.7, 4.3, and 3.3 for
the pharynx, larynx, and oral cavity, respectively. Analysis of alcohol use by
consumption frequency showed incr risks with incr exposure. With the alcohol use
(drinks/day) categories of 0, 1 to 2, 3 to 6, or > 6, the chromosome damage
odds ratios were 1.0, 1.9, 5.0, and 44.5, respectively.
Groups of 10 male Swiss mice
were admin either 2 g/kg ethanol or distilled water ip simultaneously with a
contralateral ip injection of the selective alpha2-adrenoceptor antagonists
atipamezole (1 or 3 mg/kg) or idazoxan (1 or 3 mg/kg), or distilled water. In
expt 2, groups of 8 to 10 Swiss mice were admin ether 2 g/kg ethanol
simultaneously with a contralateral ip injection of either 0.03, 0.1, 1.0 mg/kg
atipamezole or distilled water. In expt 3, mice were admin either 2 g/kg ethanol
or distilled water (ip) at the same time as a contralateral injection of Ro
15-4513 (3 or 10 mg/kg). Ethanol significantly reduced (p < 0.001) core
temperature, while both a2-adrenoceptor antagonists were without effect when
admin alone. However, both the 1 and 3 mg/kg doses of atipamezole significantly
(p < 0.05) attenuated the ethanol induced reduction in body temperature 20
and 40 min after admin. The 3 mg/kg dose of idazoxan (but not the 1 mg/kg dose)
also significantly (p < 0.05) attenuated ethanol's hypothermic effect 20 min
after admin but this effect was not statistically significant at 40 min. In expt
2, using lower doses of atipamezole, attenuation of ethanol-induced hypothermia
caused by atipamezole was found to be dose related. The benzodiazepine inverse
agonist Ro 15-4513 possessed an intrinsic hypothermic action (p < 0.001) but
neither attenuated nor enhanced the hypothermic effect of ethanol.
The effects of 6 wk of heavy
ethanol (liquid diet of 36% ethanol) and moderate ethanol (liquid diet of 3.6%
ethanol) feeding to male Wistar rats upon lipids and lipoprotein metabolism were
determined. As compared to the control group (rats fed isocaloric amounts of
dextrimaltose in place of ethanol), the heavy ethanol feeding resulted in the
following changes: liver wt/kg body wt incr by 48% with a concomitant 52% incr
in liver protein/kg body wt and a 2.75-fold incr in liver total lipids/kg body
wt. In contrast, liver DNA/kg body wt or per liver was not affected
significantly. Plasma cholesterol and triglycerides were higher by 53% and 77%,
respectively. Liver cholesterol and triglycerides were 4.4-fold and 3.8-fold
higher, respectively. Plasma total A1 was 1.72-fold higher 0.001), whereas there
was no significant difference in plasma apo E levels between the two groups.
However, plasma high density lipoproteins (HDL) apo E was 48% lower while the
very low density lipoproteins (VLDL) E was 2.15-fold higher. Hepatic total
protein synthetic rate in the ethanol group was not significantly different from
the control group. In contrast, labeled leucine incorporation into the total
secretory proteins was inhibited by 36% in the ethanol fed group. Specifically,
inhibitions of the synthetic rates of various secretory proteins in the ethanol
group compared to the control group were as follows: by 55% for total VLDL
apoproteins, by 44% for apo A1 protein, by 55% for total apo E proteins, by 62%
for VLDL apo E, by 52% for HDL apo E and by 50% for transferrin. In contrast,
moderate ethanol feeding for six wk did not alter any of the above parameters.
The modifying effect of
ethanol on aflatoxin B1 (AFB1)-induced hepatocarcinogenesis was examined in male
ACI/N rats by chronic treatment at the post initiation phase. Rats received an
ip injection of AFB1 (1.5 mg/kg) twice a wk for 10 wk (a total of 20 doses).
Following a wk of acclimation, they were given 10% ethanol as drinking water for
56 wk. The effects of ethanol on hepatocarcinogenesis were evaluated in terms of
the incidence of altered hepatocellular foci and neoplasms at the end of the
experiment. Exposure to AFB1 alone induced a substantial number of altered foci
(6.98 iron excluding foci/sq m) in rats. The number of altered liver cell foci
in rats receiving AFB1 followed by ethanol was significantly incr (26.39 iron
excluding foci/sq cm). In the rats given ethanol after AFB1, the total area and
mean diameter of both iron excluding foci and altered foci identified in
hematoxylin and eosin-stained sections were significantly higher than in the
rats exposed to AFB1 alone. The incidence of liver cell tumors of the group
given AFB1 and ethanol (3/15, 20%) was higher than that of the group treated
with AFB1 alone (0/14, 0%). Treatment with ethanol alone for 56 wk did not
induce either.
The effect of nicotine and
nicotine/ethanol were examined using a 4-hr perfused human placental system and
human placental vesicles. Placental systems and vesicles from nonsmokers were
exposed to 'physiological' (0.2 uM) and large (about 20 uM) nicotine concn
alone, as well as nicotine combined with 200 or 400 mg/ml ethanol, for 5 min, 24
hr, and 48 hr. Two nonmetabolizable amino acids, alpha-aminoisobutyric acid and
cycloleucine were used as probes. The maternal compartment half-life of nicotine
was 2.12 hr without ethanol and 2.65 hr with addition of ethanol. There was no
statistically significant evidence of decr transport of these amino acids with
exposure in either test system. There was no evidence of altered transport of
antipyrine, nonspecific leakage of water or difference in lactate output, or
glucose consumption with exposure of the perfused placenta to either nicotine or
nicotine/ethanol.
Groups of 6 to 12 male CD-1
mice were given an ip injection of the anticonvulsive drug carbamazepine (10,
15, or 20 mg/kg) or propylene glycol (vehicle) 10 min before ip admin of 1.0,
1.5, 2.0, 2.5, or 4.0 g/kg ethanol in saline. Whereas mice that received 1.5
g/kg ethanol regained their normal motor coordination within 45 min of ethanol
admin, only 85 and 75% of normal motor coordination was recorded in mice
injected with 2 and 2.5 g/kg ethanol respectively, at 60 min post-ethanol.
Carbamazepine significantly potentiated the motor incoordinating effect of 2
g/kg ethanol in a dose-dependent fashion. Motor coordination was only 35 and 20%
of normal at 15 and 20 mg/kg carbamazepine, even at 60 min post-ethanol.
Although carbamazepine did not alter the onset time, it significantly prolonged
the duration of ethanol induced loss-of-righting reflex. 15 mg/kg carbamazepine
significantly prolonged the duration of loss-of-righting reflex produced by 4
g/kg ethanol (hypnotic dose), compared to the saline + ethanol group, 102 vs
38.0 min, respectively. Pretreatment with theophylline (25 and 50 mg/kg)
significantly attenuated the carbamazepine induced potentiation of both effects.
50 mg/kg theophylline markedly attenuated the potentiation on ethanol induced
motor incoordination by carbamazepine (15 and 20 mg/kg) at all post-ethanol time
periods. Results from a blood ethanol study indicated no effect of carbamazepine
on the clearance of ethanol.
In Sprague-Dawley rats having
relatively little experience in the open field, the actions of ethanol (0.75
g/kg ip), Ro15-4513, an imidazobenzodiazepine partial inverse antagonist, (1.25
mg/kg and 2.5 mg/kg, ip), and Ro15-4513 in combination with ethanol were
measured on horizontal activity. Rats receiving ethanol showed a significant
depression in horizontal activity. Doses of Ro15-4513 given alone (n = 14)
produced no significant differences in activity from baseline levels. Rats (n =
8) pretreated with Ro15-4513 prior to receiving ethanol, however, showed a
significant attenuation of the ethanol induced depression of activity.
The interactions of cocaine
with ethanol in nontolerant and ethanol-hypnosis tolerant male Sprague-Dawley
rats were examined. Cocaine pellets (12.5 mg) implanted sc in rats potentiated
the hypnosis induced by ethanol (3.2 g/kg ip) and the implantation of the same
type of pellets (12.5, 25 mg) in ethanol tolerant rats restored the ethanol
hypnosis to levels observed in acutely treated animals.
Serotonin-stimulated
activation of phospholipase C in primary astroglial cell cultures made from
newborn Sprague-Dawley rats was studied as a mean of evaluating the effect of
acute ethanol exposure on this signal transduction system. The addition of
50-150 mM ethanol prior to stimulation with 10-5 M serotonin led to a
potentiation of the serotonin-induced (3H)-inositol phosphate formation and an
incr incorporation of (3H)-inositol into the three phosphoinositides studied.
The potentiating effect of ethanol was observed only when ethanol was added
together with serotonin. Ethanol had no effect on arginine-vasopressin,
bradykinin or phenylephrine-stimulated inositol lipid metabolism.
The effects of cadmium (100
ppm through drinking water) and ethanol (5 g/kg by gastric gavage)
administration on biogenic amines, metal distribution and certain enzymes in
male Wistar rat brain was investigated after 90 days of exposure. Co-exposure
group revealed significant accumulation of cadmium and also incr in zinc levels
compared to all the other groups. Ethanol alone decr monoamine oxidase activity
and incr norepinephrine and 5-hydroxytryptamine levels, while in combination
with Cd, these effects were more magnified.
Male CD-1 mice were given a
series of tones paired with footshock in the closed arm of a Y maze. On a test
session 8 days later the animals were tested for retention of the conditioned
emotional response (CER). On the 2-min test session, the three arms of the maze
were open and the number of entries into the arms was counted. Retention of the
conditioned emotional response was measured by the decr in the number of entries
in comparison with mice trained with no footshock. Starting 24 hr after
training, and continuing for the 7 days between training and testing, the
animals in different groups received a daily ip injection of saline, 3.6 g/kg of
ethanol, 150 ug/kg of the cholinergic muscarinic agonist oxotremorine, or
ethanol plus oxotremorine. Retention was evaluated 24 hr after the last
injection. Ethanol reduced retention of the conditioned emotional response. This
effect was attenuated by oxotremorine (150 ug/kg) given ip 6 min prior to
testing, but not by the same dose of oxotremorine given daily together with the
ethanol treatment. Oxotremorine injections administered prior to the retention
test also enhanced the retention performance of the control group. Daily
oxotremorine administration had no effect.
The effects of methyl n-butyl
ketone (2.5, 3.75, and 5.0 mmol/kg ip), methyl isobutyl ketone (2.5 and 5 mmol/kg
ip), methyl ethyl ketone (5, 10, and 15 mmol/kg ip) and acetone (10, 20, and 40
mmol/kg ip) on the duration of ethanol-induced loss of righting reflex and on
ethanol elimination in male CD-1 mice were studied. The solvents were dissolved
in corn oil and injected ip 30 min before ethanol 4 g/kg ip. The 4 solvents
prolonged significantly the duration of ethanol induced loss of righting reflex
when given in the following doses (mmol/kg): methyl n-butyl ketone, 3.75 and 5
(mean time = 11.5 min); methyl isobutyl ketone, 5: methyl ethyl ketone, 5 and
10, acetone, 20 and 40. This prolongation was dose related and increased as the
dose of the solvent was increased. A dose of 40 mmol/kg acetone resulted in
ataxia in all mice treated with this dose. The concn of ethanol in blood or
brain (approx 2.5 to 3.5 mg/ml or mg/g, respectively) on return of the righting
reflex were similar in solvent treated and control animals, with the exception
of the group of mice treated with 40 mmol/kg acetone in which the ethanol concn
were significantly lower than in control animals. The mean elimination rate of
ethanol was markedly reduced (from 692 mg/hr/kg for controls) in mice treated
with methyl n-butyl ketone 5 mmol/kg (523 mg/hr/kg), methyl ethyl ketone 15 mmol/kg
(575 mg/hr/kg), and acetone 40 mmol/kg (386 mg/hr/kg). All 4 solvents reduced
the activity of mouse liver alcohol dehydrogenase in vitro. The admin of 2,5
hexanedione (0.75 mmol/kg ip) did not alter the duration of ethanol induced loss
of righting reflex, nor did it affect the concn of ethanol in the blood or brain
on return of the righting reflex. Admin of 2-hexanol (2.5 mmol/kg ip)
significantly prolonged the duration of ethanol induced loss of righting reflex
but did not affect ethanol concn in the blood or brain on return of the righting
reflex.
To determine whether or not
the previously reported association between alcohol (ethanol) intake and high
blood pressure is influenced by differential intake of calcium and potassium in
drinkers compared with nondrinkers and to assess the magnitude of the
independent contributions of alcohol, calcium, and potassium to blood pressure,
these associations were evaluated in 7,011 men of Japanese descent. Alcohol
consumption above a threshold of approx 20 ml/day was found to be positively,
strongly, and independently correlated with systolic and diastolic pressures,
and this effect was completely independent of the effects of calcium and
potassium. Calcium and potassium intake were highly correlated and were
inversely related to blood pressure, and their combined effect was greater than
the effect of either alone. However, in the subgroup of moderate and heavier
drinkers, only potassium was inversely related to blood pressure. This finding
is compatible with previous reports of malabsorption and incr excretion of
calcium at higher levels of alcohol intake, and it indicates that a small
portion of the alcohol-induced blood pressure elevation may be mediated through
calcium depletion. In the range of dietary intake in this cohort, the effect of
alcohol on blood pressure was stronger than was either the separate or combined
effects of calcium and potassium.
Groups of 8 male albino rats
were given water ad lib and assigned to one of the following treatments, 6
days/wk for 4 mo: (Group 1) no treatment (control); (Groups 2 to 4) 1, 2, and 5
g/kg ethanol, once by gastric gavage; (Group 5) lead as lead acetate, 0.55 g/l
in drinking water; (Groups 6 to 8) 1, 2, and 5 g/kg ethanol, once by gastric
gavage plus lead as 0.55 g/l lead acetate in drinking water. Ethanol or lead
when given alone inhibited the activity of blood gamma-aminolevulinic acid
dehydratase (p < 0.05 compared to control for all levels after 2 mo
treatment). Ethanol caused a dose-dependent incr in hepatic lipid peroxidation,
which was more marked after 4 mo co-exposure to lead and ethanol. The
co-administration of 5 but not 1 or 2 g/kg ethanol significantly enhanced the
lead-induced inhibition of blood gamma-aminolevulinic acid dehydratase activity
and the elevation of gamma-aminolevulinic acid excretion (p < 0.05). Exposure
to lead and ethanol (5 g/kg) produced a more pronounced incr in hepatic lipid
peroxidation and blood glucose level than either ethanol or lead alone.
Co-exposure to ethanol did not affect the lead-induced incr in blood zinc
protoporphyrin except at 5 g/kg after 4 mo exposure, when the level was
significantly higher than in the lead group (p < 0.05). This combination also
caused a significant incr in the dopamine contents of striatum, midbrain and
pons medulla, norepinephrine contents in midbrain and 5-hydroxytryptamine
contents of hypothalamus, striatum, midbrain and pons medulla over levels
produced by lead alone. However, the level of norepinephrine in hypothalamus
decr upon co-administration. The uptake and retention of lead was significantly
(p < 0.05) higher in blood, liver, kidney and brain in animals co-exposed to
lead and 5 g/kg ethanol. Blood and kidney lead was also increased by 2 g/kg
ethanol (p < 0.05).
The effects of ethanol on
releasable Ca stores were examined in microsomes isolated from ICR mouse whole
brains. Ca release was monitored by detn of changes in the extra-microsomal Ca
concn using Indo-1, a fluorescent Ca indicator. In the absence of ATP, ethanol
released Ca from microsomes in a concn dependent manner, with a threshold for Ca
release between 25 and 50 mM. A 50 mM concn of ethanol released about 0.5 nmol
of Ca per mg of microsomal protein. The highest concn of ethanol (400 mM)
released approx 5 nmol Ca/mg microsomal protein. Release was maximal within 10
sec. Ethanol induced release of microsomal Ca was reduced by approx 50% after
ATP stimulated uptake of Ca, indicating that the ethanol releasable pool was
diminished by ATP dependent uptake of Ca into an ethanol insensitive microsomal
pool. Release of Ca produced by ethanol was linear with concn (25 to 400 mM). Ca
release induced by ethanol was not altered by incr the temp from 15 to 25 C.
However, incr the temp from 25 to 32 C and from 32 to 36 C produced a large incr
in the ability of ethanol to release Ca. Simultaneous addition of ethanol and
inositol 1,4,5-triphosphate produced additive responses.
Intranasal cocaine and oral
ethanol (ETOH) were admin to nine male subjects (21-45 yr) during daily exptl
sessions. In 3 hr sessions (5 days), a 14 min period of resting baseline was
followed by the exptl session which consisted of 10 min of task performance,
admin of ETOH (0, 19.4, 38.7, or 58.1 g), 35 min of ETOH baseline, admin of
cocaine HCl (4, 48, 96 mg), 20 min of ETOH and intranasal cocaine baseline, 10
min of task performance, 40 min of resting, 10 min of task performance, and 6
min of resting. Intranasal cocaine increased resting heart rate and blood
pressure, and oral ETOH increased resting heart rate and decreased resting blood
pressure.
Pharmacology:
Therapeutic Uses:
Anti-Infective Agents, Local;
Central Nervous System Depressants; Solvents
ALCOHOL IS FREQUENTLY EMPLOYED
FOR MEDICINAL MIXTURES AS VEHICLE. ALCOHOL IS SOLVENT FOR THE TOXICODENDROL
CAUSING IVY POISONING; EARLY AND THOROUGH WASHING OF THE AFFECTED PARTS WITH
ALCOHOL MAY ABORT OR LESSEN SEVERITY OF DERMATITIS. IN PHENOL SKIN BURNS ALCOHOL
SHOULD BE USED IMMEDIATELY AS A WASH IF CASTER OIL IS NOT AVAILABLE ... ALCOHOL
COOLS THE SKIN WHEN IT IS ALLOWED TO EVAPORATE, AND ALCOHOL SPONGES ARE
THEREFORE USED TO TREAT FEVER. IT IS ALSO RUBEFACIENT & IS INCL IN
LINIMENTS. ALCOHOL (50 TO 70% BY VOL) IS EMPLOYED AS A RUBBING AGENT ON THE SKIN
OF BEDRIDDEN PT IN ORDER TO PREVENT DECUBITUS ULCERS. IT IS ALSO USED TO DECR
SWEATING, AND IS AN INGREDIENT OF MANY ANHIDROTIC AND ASTRINGENT LOTIONS. ETHYL
ALCOHOL STILL REMAINS THE MOST POPULAR SKIN DISINFECTANT. ... ALCOHOLIC
BEVERAGES ... MAY BE GIVEN BEFORE MEALS AS STOMACHIC TO IMPROVE APPETITE &
DIGESTION, ESP IN CONVALESCENT & DEBILITATED OR ELDERLY PT. ... ALCOHOL ACTS
AS HYPNOTIC & ANTIPYRETIC ... ALCOHOLIC BEVERAGES HAVE BEEN USED TO CHECK
IMPENDING "HEAD COLDS". ... MAKES PT DROWSY & SLEEPY ... .
... IT HAS BEEN OCCASIONALLY
ADMIN IV FOR PREOPERATIVE & POSTOPERATIVE SEDATION IN PT IN WHOM OTHER
MEASURES ARE INEFFECTIVE OR CONTRAINDICATED. DOSE EMPLOYED IS 1 TO 1.5 ML/KG. IV
USE ... IS SPECIALIZED PROCEDURE & SHOULD BE EMPLOYED ONLY BY ONE
EXPERIENCED IN ... SUCH USE.
ETHANOL IN FORM OF 7% SOLN IS
USED AS GASTRIC FUNCTION TEST. ... 50 ML OF 7% ETHANOL IS SWALLOWED WITH TUBE
REMAINING IN PLACE. SEVERAL 10-15 ML SAMPLES OF GASTRIC CONTENTS WITHDRAWN ...
& SECRETORY CURVE IS PLOTTED.
ETHANOL IS AN IMPORTANT ADDN
TO ... LOCAL ANTIINFECTIVE DRUGS BECAUSE OF ITS ABILITY TO SOLUBILIZE FAT &
EXERT SYNERGISTIC OR ADDITIVE EFFECT WHEN USED IN COMBINATION WITH OTHER
ANTISEPTICS OR DISINFECTANTS.
ALCOHOL INJECTIONS /OF
ETHANOL/ INTO ORBIT HAVE BEEN USED FOR MANY YEARS FOR LONG LASTING RELIEF OF
SEVERE OCULAR OR NEURALGIC PAIN. MOSTLY RETROBULAR INJECTIONS HAVE BEEN USED AS
AN ALTERNATIVE TO ENUCLEATION OF BLIND PAINFUL EYES, BUT WITH PROPER TECHNIQUE
THEY CAN BE USED WITHOUT EXCESSIVE DANGER WITH SEEING EYES.
DEHYDRATED ETHANOL MAY BE
INJECTED IN CLOSE PROXIMITY OF NERVES OR SYMPATHETIC GANGLIA FOR RELIEF OF LONG
LASTING PAIN THAT OCCURS IN TRIGEMINAL NEURALGIA, INOPERABLE CARCINOMA, &
OTHER CONDITIONS. EPIDURAL, SUBARACHNOID, & LUMBAR PARAVERTEBRAL INJECTIONS
OF ALCOHOL HAVE ALSO BEEN EMPLOYED ... .
MEDICATION (VET): ANTISEPTIC,
RUBEFACIENT, STOMACHIC, SEDATIVE, ANESTHETIC, NUTRIENT, VASODILATOR, SURFACTANT.
... IS ANTIDOTE OF CHOICE IN ETHYLENE GLYCOL (ANTIFREEZE) POISONING ... 70% SOLN
... TOPICAL ANTISEPTIC STRENGTH. 5% SOLN FOR IV USE.
MEDICATION (VET): ETHANOL HAS
BEEN INJECTED FOR ALLEVIATION OF PAIN IN LAME HORSES, AND OCCASIONALLY IT HAS
BEEN INJECTED EPIDURALLY IN CATTLE TO HELP CORRECT CHRONIC VAGINAL AND/OR RECTAL
PROLAPSE.
THE COMMON BIOCHEMICAL PATHWAY
OF OXIDATION OF BOTH METHANOL AND ETHANOL ... ACCOUNTS FOR THE CLINICAL
OBSERVATIONS THAT SIMULTANEOUS ADMIN OF ETHANOL MAY AMELIORATE THE TOXIC
SEQUELAE OF METHANOL POISONING.
INTRAVENOUS ETHANOL, ONCE
WIDELY USED TO INHIBIT PREMATURE LABOR, HAS BEEN REPLACED BY BETA-ADRENERGIC
THERAPY. THE PROPOSED MECHANISM OF ALCOHOL INDUCED UTERINE RELAXATION INVOLVES
THE INDIRECT INHIBITION OF THE /UTERINE/ MYOMETRIUM BY PREVENTING OXYTOCIN'S
RELEASE FROM THE POSTERIOR PITUITARY GLAND.
MEDICATION (VET): TO DESTROY
NERVE TISSUE
The subarachnoid injection of
alcohol in 322 pt with intractable pain from malignant disease gave long lasting
marked relief in 187 and partial relief in 84.
The equivalent of 50 ml of
alcohol reduced intraocular pressure in glaucomatous pt by up to 30 mm Hg. ...
This effect had been used prior to surgery in 2 pt unable to tolerate other
agents.
Drug Warnings:
BRIEFLY APPLIED TO THE SKIN,
70% ALCOHOL DOES NO DAMAGE, BUT IT IS IRRITATING IF LEFT ON FOR LONG PERIODS OF
TIME. AS THE RESULT OF REMOVAL OF CUTANEOUS LIPIDS, FREQUENT USE CAUSES DRY SKIN
AND SCALINESS. IRRITATION IS SOMETIMES CAUSED BY DENATURANTS IN ETHANOL. APPLIED
TO WOUNDS OR RAW SURFACES, ETHANOL NOT ONLY INCR INJURY BUT ALSO FORMS A
COAGULUM UNDER WHICH BACTERIA MAY SUBSEQUENTLY THRIVE. IT IS THUS NOT USED TO
DISINFECT OPEN WOUNDS.
Ethanol potentiates the
central nervous system effects of numerous sedative and depressant drugs. ... It
should not be used by patients taking certain prescription drugs ... .
Maternal Medication usually
Compatible with Breast-Feeding: alcohol (ethanol): Reported Sign or Symptom in
Infant or Effect on Lactation: With large amounts drowsiness, diaphoresis, deep
sleep, weakness, decrease in linear growth, abnormal weight gain; maternal
ingestion of 1 g/kg daily decreases milk ejection reflex. /from Table 6/
Interactions:
CONCURRENT INGESTION OF
CHLORAL HYDRATE & ALCOHOL RESULTS IN GREATER CNS DEPRESSION ... CHLORAL
BETAINE, TRICLOFOS, & OTHER /RELATED/ PRODUCTS METABOLIZED TO YIELD
TRICHLOROETHANOL WILL INTERACT WITH ALCOHOL.
CONCURRENT INGESTION OF
MEPROBAMATE & ALCOHOL CAN LEAD TO ENHANCEMENT OF ... CNS DEPRESSANT EFFECTS.
EFFECTS OF AMITRIPTYLINE &
RELATED TRICYCLIC ANTIDEPRESSANTS ON ALCOHOL ARE UNPREDICTABLE.
... ALL BARBITURATES INTENSIFY
DEPRESSANT EFFECTS OF ALCOHOL.
CONCURRENT INGESTION OF
ASPIRIN & ALCOHOL MAY ENHANCE OCCULT BLOOD LOSS & GASTRIC DAMAGE INDUCED
BY ASPIRIN. ... MOST FORMS OF SALICYLATES MAY INTERACT WITH ALCOHOL ... .
... PT TREATED WITH ORAL
HYPOGLYCEMIC AGENTS MAY EXPERIENCE UNPLEASANT SYMPTOMS SIMILAR TO THOSE
EXPERIENCED BY PT WHO TAKE DISULFIRAM AFTER INGESTION OF ALCOHOL. SIMILAR
INTERACTIONS CAN OCCUR WITH METRONIDAZOLE OR CEPHALOSPORINS. ... THE
HYPOGLYCEMIC EFFECT OF INSULIN MAY ALSO BE MARKEDLY INCR. ALCOHOL CAN INTERFERE
WITH THE THERAPEUTIC ACTIONS OF A WIDE VARIETY OF DRUGS BY ALTERING THEIR
METABOLISM. ... ACUTE INGESTION OF ETHANOL REDUCES THE CLEARANCE OF PHENYTOIN
BECAUSE BOTH DRUGS COMPETE FOR THE SAME HEPATIC MICROSOMAL OXIDASE SYSTEM.
ALCOHOL MAY ALSO INTERFERE
WITH THERAPEUTIC ACTIONS OF ... COUMARIN TYPE OF ANTICOAGULANT ... .
16 HEALTHY VOLUNTEERS TOOK
PART IN A CROSSOVER STUDY EXAMINING THE EFFECT OF ETHYL ALCOHOL ON THE RATE OF
SULFAMETHAZINE ACETYLATION. APPARENT HALF-LIFE OF DRUG DECR BY ABOUT 20% AFTER
ETHANOL AND AMT OF DRUG ACETYLATED, MEASURED IN BLOOD & URINE, INCREASED.
IN MICE & RATS,
METHAQUALONE DELAYED DISAPPEARANCE OF ETHANOL IN BLOOD & BRAIN OVER A PERIOD
OF 50 TO 200 MIN AFTER A LOADING DOSE OF 2.0 G/KG, IP OF ETHANOL. METHAQUALONE @
140 AND 200 MG/KG INCR ETHANOL TOXICITY BY 11% AND 28%, RESPECTIVELY. CO-ADMIN
OF ETHANOL USING 6.0, 7.0, AND 8.0 G/KG ALSO REDUCED THE LD50 OF METHAQUALONE BY
19, 24, AND 40%, RESPECTIVELY. CHRONIC ETHANOL ADMIN DECR METHAQUALONE TOXICITY.
COADMIN OF
ALPHA-1-ACETYLMETHADOL @ 18 OR 36 MG/KG POTENTIATED ETHANOL TOXICITY; LD50 DUE
TO ETHANOL WAS LOWERED BY 21 & 36%, RESPECTIVELY. ETHANOL (0.5 & 1 G/KG)
DECR ALPHA-1-ACETYLMETHADOL TOXICITY; LD50 WAS INCR TO 76 AND 64 MG/KG,
RESPECTIVELY, COMPARED WITH 56 MG/KG FOR ALPHA-1-ACETYLMETHADOL ALONE. AT 4 G/KG
ETHANOL, LD50 WAS DECR TO 43.9 MG/KG, SHOWING POTENTIATION OF INTERACTION
TOXICITY.
DIABETIC PT TREATED WITH
PHENFORMIN SHOULD AVOID INGESTION OF ALCOHOLIC BEVERAGES BECAUSE CONCURRENT USE
MAY CAUSE HYPOGLYCEMIC REACTIONS OR LEAD TO LIFE THREATENING LACTIC ACIDOSIS
WITH SHOCK.
In hamsters given ethanol in
drinking water and also given the known pancreatic carcinogen
N-nitrosobis(2-oxopropyl)amine (20 mg/kg, sc) no neoplastic lesions were
observed at the end of the expt, whereas 11 of 14 hamsters given the carcinogen
alone showed neoplastic lesions. Lipase activity was reduced in hamsters given
the carcinogen but was normal in the ethanol + carcinogen treated animals.
A serious, relatively
unrecognized occupational health problem involves the interaction of ethyl
alcohol and chem agents used in industry. Workers who drink alcohol and are
exposed to certain chem agents may experience adverse health effects such as
nausea, dizziness, headache and liver damage. The synergistic interactions of
ethanol with cmpd such as the thiurams, amides, oximes, halogenated hydrocarbons
and metals were reviewed.
The influence of several
neotropic drugs (piracetam, pyritinol, meclofenoxat, methylglucamine orotate (MGO)
and dihydroergotoxine (DHET)) on both the ethanol preference and the enhanced
seizure susceptibility after a single dose of ethanol was studied. Piracetam,
MGO and DHET reduce the ethanol drinking in ethanol preferring mice. The
enhanced seizure susceptibility after a single dose of ethanol was abolished by
piracetam and MGO.
The ascending noradrenergic
pathways from the locus coeruleus were lesioned bilaterally in 10 rats by
intracerebral 6-hydroxydopamine injections. Ten rats were sham operated. All
animals were subjected to a 4 day ethanol intoxication period using intragastric
intubation. Intoxication and withdrawal assessments were performed blindly. The
6-hydroxydopamine lesions did not appear to affect tolerance to ethanol. During
withdrawal, however, lesioned animals showed minor, but statistically
significant changes in scores of certain non-convulsive withdrawal signs, but
incidence and intensity of spontaneous and audiogenic convulsive seizures were
not different between the groups.
A fatal case of multiple drug
abuse in a 36 year old veterinarian involving injection of xylazine and
ingestion of alcohol and clorazepate is presented. Quantitative analysis of
xylazine was by gas liquid chromatography with a nitrogen detector. Xylazine
concentrations (mg/l or mg/kg) were: blood, 0.2; brain, 0.4; kidney, 0.6; liver,
0.9; lung, 1.1; omentum adipose 0.05; and urine, 7.0. Blood ethanol and
nordiazepam concentrations were 380 mg/dl and 2.5 mg/l, respectively.
A pharmacokinetic study was
conducted to determine the effectiveness of lower doses of ethanol in the
treatment of ethylene glycol (EG) poisoning. Four dogs were maintained at serum
ethanol concentrations of 0, 35 and 140 mg/dl prior to EG (iv, 2 ml/kg)
administration. The serum EG concentration-time data showed that the 35 mg/dl
ethanol level provided as effective an inhibition of EG metabolism as did the
140 mg/dl level. The average urinary excretion rate of oxalic aid post EG
administration was reduced to control levels by ethanol. The 35 mg/dl serum
ethanol level reduced the total body clearance of EG from 93.9 to 50.0 ml/hr/kg
and increased the effective half-life from 5.78 to 11.4 hr. Clinical testing was
accomplished by giving the dogs 12 ml EG/kg body weight orally. One hour later,
the dogs were either not treated or treated with a sodium bicarbonate-ethanol
solution to obtain a serum ethanol concn of 50 mg/dl. The clinical test
performed in the ethanol-treated dogs showed little change from normal limits.
Urine calcium oxalate crystals were seldom found. The dogs given EG (12 ml/kg)
but not treated with ethanol were in a coma at 13 hr and showed severe metabolic
acidosis, dehydration, mild hepatocellular disease, and acute renal damage.
Urine calcium oxalate crystals were found in high numbers. The rapid death
associated with EG poisoning appeared to be due to metabolic acidosis in
combination with dehydration.
Because alcoholism has adverse
effects on Zn nutrition and many pregnant women consume less than the
recommended dietary allowances of Zn, it was postulated that Zn deficiency acts
as a co-teratogen with alcohol in the fetal alcohol syndrome. The effects of
alcohol on progeny of pregnant mice fed a Zn deficient diet were compared to
those fed a diet containing adequate Zn. Pregnant CBA mice (n= 66) were fed the
Lieber-DeCarli liquid diet with 0, 15, or 20% ethanol derived calories
containing 0.3 (low) or 8.5 (high) mug Zn/ml. Dams were sacrificed on day 18 of
gestation. Resorptions, malformations, and individual fetal weights were
recorded. Analysis of fetuses included assays for Zn, assessment of soft tissue
malformations, and alizarin red staining for skeletal malformations. Fetal
weights were lower in the groups fed the Zn-deficient diet for each
concentration of alcohol (p < 0.005). The groups fed the combination of low
Zn plus alcohol had 37-52% resorptions, while the animals on the Zn deficient
diet without alcohol or the high Zn diet with alcohol diet had 0-2% resorptions.
Skeletal malformations were related to alcohol concn but not Zn intake, while
external malformations were higher in those maintained on the low Zn ethanol
diet. These results suggest that Zn deficiency potentiated the teratogenic
effects of alcohol and that nutritional intervention for alcoholic women during
pregnancy might reduce the incidence or severity of fetal alcohol syndrome.
The interaction of ethanol
with drugs and xenobiotics is complex because ethanol can affect any of the
following steps; absorption, plasma protein binding, hepatic blood flow,
distribution, hepatic uptake of drugs, and phase I and II hepatic metabolism.
The ingestion of ethanol can lead to malabsorption of drugs. High concn of
ethanol in conjunction with aspirin causes gastric mucosal damage. The principal
effect of acute ethanol ingestion on drug metabolism is inhibition of microsomal
drug metabolism. The synergistic effects of ethanol on central nervous system
depressants can be explained by this mechanism. In contrast, chronic ethanol
consumption increases mixed function oxidation and drug metabolism. The cross
tolerance between ethanol and sedatives in chronic alcoholics may be due to this
effect of alcohol. In addition, increased production of hepatotoxic products
from certain drugs and xenobiotics and an increased activation of procarcinogens
to carcinogens can result from this microsomal induction. The increased
susceptibility to hepatotoxins and the enhanced carcinogenesis in the alcoholic
may be explained by this fact. Other effects of the interaction between drugs
and alcohol are the result of changes in organ susceptibility, best demonstrated
for the central nervous system. Subsequently, the presence of liver disease has
a great effect upon drug metabolism in alcoholics.
Pharmacokinetic interactions
of ethanol with other drugs including its effects upon drug metabolite
disposition, are reviewed in terms of clearance concepts. This approach is
particularly useful in understanding the mechanisms of ethanol drug interactions
(ie in separating the effects of ethanol upon drug clearance, volume of
distribution and plasma protein binding.) The application of clearance concepts
provides the basis for understanding the qualitative differences in ethanol
interactions with low and high hepatic extraction ratio drugs. The effects of
short and long term ethanol consumption upon different types of drug metabolism
(oxidative, acetylation and glucuronidation) have been considered. Lomg term
ethanol consumption may increase the clearance of a drug by induction of
oxidative metabolism whereas short term consumption may decrease the clearance
of such a drug. Clearance by N-acetylation appears to be increased in the
presence of ethanol, while clearance by conjugation to glucuronic acid is
decreased for some drugs by single dose consumption of ethanol.
Hepatocytes isolated from male
Sprague-Dawley rats (Harlan, 200-275 g) were exposed to halogenated and non
halogenated hydrocarbons. Leakage of cellular enzymes and inhibition of
respiration were monitored as indicators of toxicity. Cell suspensions contained
2-3X10+6 cells/ml and were viable for 6 hr as indicated by a < 10% increment
in the fractional release of aspartate aminotransferase (AST) activity. The
hydrocarbons were added to the cell suspension as 20% solutions in ethanol. Only
3% of the AST activity was found in the medium at the beginning of the
experiment, and there was no increase with time in cells treated with ethanol
(n= 4). The relationship of the effects of cellular respiration to alteration in
mitochondrial function was studied using dinitrophenol (DNP), an uncoupler of
oxidative phosphorylation, and succinate, an NADH independent mitochondrial
substrate. Ethanol caused a decrease in the DNP stimulated oxygen consumption
(n= 5-8), but had essentially no effect on the succinate stimulated oxygen
consumption. All parameters of mitochondrial function returned to control levels
within one hr.
The effects of a combined high
glucose diet and ethanol on chronic hexachlorobenzene (HCB) intoxication were
examined using male Wistar rats. Treatments were: (1) glucose diet (63% glucose)
(n= 10), (2) glucose diet plus 17.5 mmol HCB/kg food (n= 20), (3) glucose diet
plus HCB plus 10% ethanol in the drinking water at an average of 0.104 mol
ethanol/kg body weight daily (n= 20), (4) glucose diet plus ethanol (n= 10), (5)
standard (control) diet (63% starch) (n= 30), and (6) standard diet plus HCB (n=
30). The treatment period lasted 60 days. HCB treatment produced clonic
convulsions, tremors, and hyperexcitability with symptoms appearing earlier and
more intensely in rats fed the standard diet. Ethanol itself affected only serum
enzymes, increasing them significantly. The glucose diet and ethanol exerted
contrasting effects so that the combination of glucose diet plus HCB plus
ethanol produced similar results to those obtained with the standard diet plus
HCB.
Drinking habits of rotogravure
printers exposed to toluene were not found to influence performances on
psychological examinations. Drinking habits were considered in grouping the
workers. The test battery consisted of standardized tests for verbal and visual
cognition and memory, perceptual motor speed, and psychomotor abilities. Within
the rotogravure group, workers were divided into subgroups with (A) high toluene
exposure (greater than 120 ppm) with heavy drinking, (B) high exposure with
moderate drinking, (C) low exposure with heavy drinking, and (D) low exposure
without heavy drinking. Mean test performances indicated that drinking habits
did not explain the impairment of visual cognitive abilities. Heavy drinkers
with high toluene exposure had intact performances.
The effects of a selective
5-hydroxytryptophan receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin on
ethanol preference was studied in 34 male Wistar strain rats. The rats had
access to a 6% (vol/vol) ethanol solution and water during baseline and
treatment periods. Based on the baseline recordings, 2 groups of rats were
formed: a high preference group (ethanol intake >50% of total fluid intake)
and a low preference group (ethanol intake <30%). Both groups were treated sc
with 0.125 mg/kg 8-hydroxy-2-(di-n-propylamino) tetralin twice daily for 3 days.
The treatment caused a significant reduction of ethanol consumption in the high
preference group, but no change in the low preference group.
Male and female long sleep and
short sleep mice were pretreated with ethanol at varying doses (0 to 4 g/kg) 7.5
min prior to challenge with an ED80 dose of nicotine (long sleep: 4.25 mg/kg;
short sleep: 6.25 mg/kg). Long sleep mice were more sensitive to the
anticonvulsant effects of ethanol than were short sleep mice. To assess the
effect of ethanol on the nicotine induced behavioral desensitization to nicotine
observed previously in these mice, animals were pretreated with saline,
nonanticonvulsant doses of ethanol (0.25 g/kg, 0.75 /kg or 1.5 g/kg), a
subseizure producing dose of nicotine (2.0 mg/kg) or a combination of these two
drugs 15 or 30 min prior to nicotine challenge. Ethanol enhanced the nicotine
induced behavioral desensitization in both mouse lines; however, this effect was
seen at lower ethanol doses and was more pronounced in long sleep mice. Ethanol
pretreatment did not affect brain nicotine concn in either long sleep or short
sleep mice.
The effect of acute (2.0 g/kg,
intragastrically) and chronic (8.0 to 11.0 g/kg/day for 10 days,
intragastrically) ethanol exposure on beta-endorphin in plasma, hypothalamus and
pituitary, and on catecholamines in hypothalamus and plasma, and on
corticosterone in plasma were examined in male Sprague Dawley rats. Plasma
beta-endorphin, norepinephrine and corticosterone levels were significantly incr
and dopamine was unchanged in acute and chronic ethanol treated rats. Compared
to controls, plasma epinephrine levels were incr in acute ethanol treated rats
but no significant change was observed in chronic ethanol treated rats. Plasma
dopamine was significantly decr following chronic ethanol treatment while no
significant change was observed after acute treatment. In the hypothalamus,
beta-endorphin and dopamine contents were incr and norepinephrine levels were
decr in response to ethanol exposure. Beta-endorphin levels were decr
significantly in the anterior pituitary and the neurointermediate lobe of the
pituitary in ethanol treated animals except in the neurointermediate lobe of the
chronic ethanol treated animals.
Male albino Wistar rats
trained to alternately shuttle between nose poke and lever operanda for
rewarding stimulation to the medial forebrain bundle, were tested following
intragastric intubations of ethanol (18%, 1.35 g/kg), the imidazobenzodiazepine,
Ro 15-4513 (3 mg/kg in 18% ethanol), or vehicle. The duration of the alternation
between operanda was significantly faster when the rats were intubated with
ethanol. Ro 15-4513 treatment reversed ethanol enhanced effects on reinforced
responses (p<0.05).
One group (n= 21) of male
Sprague-Dawley rats (310 to 360 g) were given gastric intubations of ethanol
soln (10% w/v), while others (controls, n= 16) received isocaloric
maltose-dextrin soln (17.5% w/v). Rats were given their soln every 8 hr for 24,
48, or 96 hr, alone or in combination with prazosin (1.0 mg/kg, every 8 hr, per
os). The initial dose of ethanol was 5 g/kg, after which the criteria for
subsequent doses were based on sign of intoxication displayed by individual
animals just prior to the dose being given. Adrenal glands of rats receiving
ethanol were larger (72.0 mg/pair after 48 hr) than those from control animal
(57.4 mg); prazosin did not affect this (74.1 mg). In contrast, concurrent
treatment with prazosin enhanced the loss of medullar catecholamines (by 60% at
24 hr) and noradrenaline (by 24% at 2 days) from hearts of rats given ethanol,
while it had no such effects in controls. Excreted quantities of catecholamines
were markedly increased in rats given ethanol and prazosin. Hearts of animals
given the combined treatment of ethanol and prazosin showed cardiomegaly at 24
hr, when there was an incr of about 20 in proportional heart wt, an incr that
persisted through the remaining 3 days of the study. At 48 hr, hearts of animals
give prazosin and ethanol were heavier than those given ethanol alone. A
significant correlation between catecholamine excretion and development of
cardiac hypertrophy was identified.
Preincubation with 2 M ethanol
inhibited L-alanine uptake, proton efflux and fermentation rates of exponential
phase cultures of Auxotrophic strain Saccharomyces cerevisiae, KD115. Ethanol's
inhibitory effect varied in yeast cells enriched with different fatty acyl
residues. Ethanol's effect gradually decreased with incr unsaturation index. It
was observed that cells enriched with polyunsaturated fatty acids acquired
greater tolerance to ethanol as compared to monounsaturated fatty acids. By
varying the degree of unsaturation of supplemented fatty acids a sequential
insertion of double bonds in yeast membrane lipid was achieved. Incr concn of
ethanol inhibited the efflux of H+ in palmitoleate and oleate enriched cells,
but caused negligible effects of H+ efflux in linoleate and linolenate enriched
cells. Percentage inhibition by ethanol of fermentative activity was reduced
with incr unsaturation. As compared to palmitoleate, oleate and linoleate the
inhibitory effect of ethanol on the fermentation rate of linolenate supplemented
cells was the least.
Male rats (n= 40) were given a
single ip injection of 30 mg azaserine/kg body wt at 19 days of age. The animals
were fed a semipurified diet high in unsaturated fat (HF, 25% corn oil) either
separately (n= 40) or in combination with ethanol (n= 40), which was provided in
drinking water from day 25 onward at a concn of 10% (w/v). A separate group
(control) was maintained on a diet low in unsaturated fat (LF, 5% corn oil).
Rats were killed after 15 mo, and their pancreas, liver and kidneys were
weighed. Dietary fat was found to enhance pancreatic carcinogenesis in rats.
Ethanol slightly enhanced the multiplicity but not the incidence of malignant
tumors (79 vs 86%). With ethanol, a nonsignificant incr in the number of
atypical acinar cell nodules (AACN) with a diameter > mm was seen. In the
high unsaturated fat + ethanol group the number of adenomas was lower than in
the high unsaturated fat group (156 vs 176), which was accompanied by
statistically nonsignificant, increase of malignant tumors (71 vs 57).
Male hamsters were injected sc
with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP)/kg body wt at 6 and 7 wk of age.
The animals were fed a semi purified diet high in unsaturated fat (HF, 25% corn
oil) either separately (n= 40) or in combination with ethanol (n= 40), which was
provided in drinking water at a concn of 10% (w/v). Ethanol was introduced at 5%
after the second carcinogen treatment, and gradually incr to 10% after 6 wk. A
separate group (control) was maintained on a diet low in unsaturated fat (LF, 5%
corn oil). Hamsters were killed 12 mo after the last BOP injection, and their
pancreas, liver an kidneys were weighed. Dietary fat was found to enhance
pancreatic carcinogenesis in hamsters. Ethanol did not influence the enhancing
effect of high unsaturated fat on the development of ductular carcinomas in
hamster pancreas. The number of tumor bearing hamsters was 25 for high
unsaturated fat + ethanol and 29 for high unsaturated fat, while total
adenocarcinomas were 35 and 37, respectively.
In urethane anesthetized
albino Wistar rats, intracerebroventricular (ICV) microinjections of 1.61x10-6
and 7.82x10-4 mol of ethanol induced cardiac arrhythmias in 65.5% of the
experiments. Cardiac disorders caused by ethanol (2.60x10-5 and 2.08x10-4 mol)
were prevented by previous ICV admin of atropine (1.43x10-7 mol) and propranolol
(3.86x10-7 mol). When toliprolol microinjections (3.38x 10-7 and 6.76x10-7) were
associated with ethanol (1.04x10-4 and 4.69x10-4 mol) arrhythmias were evident
in 4/6 expt, compared to toliprolol eliciting arrhythmia in 2/6 expt. IV
injection of ethanol (1.46x10-5 and 6.26x10-3 mol/animal) induced cardiac
arrhythmias in 85% (51 out of 60) of the expt. IV admin of atropine, toliprolol,
propranolol, phentolamine, pheniramine, cimetidine, or aprotinin 20 min prior to
ethanol failed to affect the arrhythmogenic properties of ethanol. Ethanol
(3.26x10-4 mol/kg) had no effect on the cardiac arrhythmias induced by iv
adrenaline (1.09x10-7 mol/kg. Ethanol also failed to antagonize the centrogenic
arrhythmias elicited by ICV sodium L-glutamate.
6o o [Pampulha ME, Loureiro V;
Biotechnol Lett 11 (4): 269-74 (1989)] Acetic acid inhibited fermentation in a
respiratory deficient mutant of Saccharomyces cerevisiae (IGC 3507-111) in an
exponential way. The undissociated form of the acid probably was the toxic
agent. Ethanol potentiated this effect in a synergistic exponential way.
Calculated values for inhibition constants of undissociated acetic acid
(l/moles) in the presence of three concn of ethanol (0, 5, and 10 % vol/vol) at
three pH values were: 34.0, 44.0, and 64.0, respectively at pH 3.5; 48.0 59.0,
and 85.0, respectively at pH 4.5; and 65.0, 84.0, and 101.2, respectively at pH
5.5.
... Ethanol, isopropanol, n-butanol,
sec-butanol, and tert-butanol ... exert a ... potentiating effect on the acute
inhalation toxicity of carbon tetrachloride. ... Interaction between isopropanol
& carbon tetrachloride was documented in an industrial accident ... where
workers exposed to both agents exhibited hepatotoxicity. With ethanol the
potentiation seems to be due to the presence of the unmetabolized alcohol;
however, with isopropanol the effect seems to be caused by the presence of both
unmetabolized alcohol and acetone. The results obtained with n-butanol resemble
those of ethanol, whereas with 2-butanol they resemble those of isopropanol ...
ADDING 1 G/L OF PROPAN-1-OL,
PROPAN-2-OL, BUTAN-1-OL, BUTAN-2-OL, ISOBUTANOL TO 40% ETHANOL IN ORANGE JUICE
LOWERED AND DELAYED BLOOD ETHANOL MAX IN TEN, 20-30 YR OLD MEN WHO DRANK 3.75
ML/KG OF SYNTHETIC BEVERAGE.
Adverse interactions with
alcohol: interacting drug: acetaminophen; adverse effect: incr acute
hepatotoxicity /From table/
Adverse interactions with
alcohol: interacting drug: anesthetics; adverse effect: decr effectiveness for
induction of anesthesia /From table/
Adverse interactions with
alcohol: interacting drug: antihistamines; adverse effect: incr CNS depression
with acute intoxication /From table/
Adverse interactions with
alcohol: interacting drug: benzodiazepines; adverse effect: incr CNS depression
/From table/
Adverse interactions with
alcohol: interacting drug: bromocriptine (parlodel); adverse effect: nausea,
abdominal pain /From table/
Adverse interactions with
alcohol: interacting drug: chloramphenicol (Chloromycetin); adverse effect:
minor antabuselike symptoms /From table/
Adverse interactions with
alcohol: interacting drug: cycloserine (Seromycin); adverse effect: incr
convulsions chronic abuse /From table/
Adverse interactions with
alcohol: interacting drug: disulfiram (Antabuse); adverse effect: abdominal
cramps, flushing, vomiting, psychotic episodes, confusion /From table/
Adverse interactions with
alcohol: interacting drug: isoniazid (INH); adverse effect: incr incidence of
hepatitis, decr isoniazid effect in some patients with chronic alcohol abuse
/From table/
Adverse interactions with
alcohol: interacting drug: methisazone (Marboran); adverse effect: incr
methisazone toxicity /From table/
Adverse interactions with
alcohol: interacting drug: metronidazole (Flagyl); adverse effect: mild antabuse
like symptoms /From table/
Adverse interactions with
alcohol: interacting drug: narcotics; adverse effect: incr CNS depression with
acute intoxication /From table/
Adverse interactions with
alcohol: interacting drug: phenothiazines; adverse effect: incr CNS depression
/From table/
Adverse interactions with
alcohol: interacting drug: phenytoin (Dilantin); adverse effect: decr
anticonvulsant effect with chronic alcohol abuse /From table/
Adverse interactions with
alcohol: interacting drug: propranolol (Inderal); adverse effect: masks
tachycardia and tremor of alcoholic hypoglycemia /From table/
Adverse interactions with
alcohol: interacting drug: quinacrine (Atabrine); adverse effect: minor antabuse
like symptoms /From table/
Ethanol enhances the effects
of coumarin anticoagulants ... insulin, monoamine oxidase inhibitors ...
Disulfiram like intolerance to ethanol may occur from sulfonylureas,
thiocarbamates, metronidazole, tolazoline, furazolidone, chloramphenicol, and
quinacrine.
In a group of patients
receiving aminosalicyclic acid for hyperlipidemia, the three pt who ingested
ethanol developed a diminished hypolipidemic response.
Chronic ethanol abuse can
produce induction of hepatic microsomal enzymes resulting in enhanced antipyrine
metabolism. ... It is proposed that the activity of alcohol dehydrogenase can be
enhanced by incr ascorbic acid saturation. In healthy volunteers, the clearance
of ethanol was slightly enhanced by ascorbic acid admin (1 g/day for 2 wk).
It is proposed that prolonged
intake of large amt of ethanol may enhace the metabolism of chloroform to
hepatoxic metabolites. ... Cimetidine probably inhibits hepatic ethanol
metabolism and/or incr the gastrointestinal absorption of ethanol.
A case has been reported in
which ethanol may have contributed to the psychotoxic reaction in an ethionamide
treated patient.
One would expect additive CNS
depression with combined use of ethanol and glutethimide. Pharmacokinetic
interaction has also been suggested. ... Acute intoxication with ethanol appears
to inhibit meprobamate metabolism while chronic ethanol ingestion appears to
induce hepatic microsomal enzymes resulting in enhanced meprobamate metabolism.
... Ethanol and metoclopramide may exhibit additive sedative effects.
Ethanol produces vasodilation,
which may enhance the orthostatic hypotension of guanethidine.
It has been proposed that
ethanol may enhance the possibility of methotrexate induced hepatotoxicity.
Hypotension reportedly may
occur following the combined use of ethanol and nitroglycerin. This is
presumably due to the vasodilation which both agents may produce.
Ingestion of alcohol
reportedly enhances the degradation of "all penicillins" but no
supporting clinical evidence is given.
Ethanol appears to enhance the
acetylation of procainamide in the liver.
A disulfiram like reaction
reportedly may occur following ethanol ingestion in pt receiving procarbazine.
Additive CNS depression may also occur.
Sulfonamides reportedly incr
the adverse effects of ethanol and further impair driving ability. However, no
supporting clinical data are given so that the clinical significance cannot be
assessed.
A small amt of admin
tetrachloroethylene is absorbed from the gastrointestinal tract, resulting in
CNS depression. This effect may be additive with that of alcohol.
Chronic ingestion of large amt
of ethanol may result in induction of hepatic microsomal enzymes. Since
doxycycline is metabolized by the liver, its metabolism may be enhanced in
alcoholic pt.
Industrial exposure to
trichloroethylene has been associated with ethanol intolerance ...
CD 1 mice were treated ip on
day 10 of gestation with 4, 6, or 7 g/kg ethanol. Ethanol rapidly crossed the
placenta and appeared in the embryo 5 min after treatment. Acetaldehyde was
detectable in maternal blood following all treatments and in maternal liver and
embryos following treatment with 7 g/kg ethanol. Coadministration of 100 mg/kg
4-methylpyrazole, an alcohol dehydrogenase inhibitor, with 4 or 6 g/kg ethanol
on day 10 of gestation significantly reduced the rate of ethanol elimination in
all tissues examined. These data suggest that both ethanol and acetaldehyde are
accessible to the embryo during a critical period of development.
IP ADMIN OF ETHANOL
(0.7-1.8 MG/G/DAY FOR 7 DAYS) TO MICE DECR LEVEL OF HEPATIC MICROSOMAL
CYTOCHROME P450, ARYLHYDROCARBON HYDROXYLASE, & PROTEIN. ORAL ETHANOL (10%
IN DRINKING WATER, 2-8 WK) DECR MICROSOMAL PROTEIN CONTENT, THEN INCR IT; P450
INCR, ARYLHYDROCARBON HYDROXYLASE DECR. IN MICE PRETREATED BOTH ORALLY & IP
WITH ETHANOL THE BINDING OF BENZO(A)PYRENE (B(A)P) TO DNA INCR. MORE TUMORS
DEVELOPED IN PRETREATED MICE GIVEN B(A)P THAN IN CONTROLS GIVEN ONLY B(A)P.
PRETREATED MICE HAD MUSCLE TUMORS, CONTROLS HAD MAMMARY TUMORS.
Ethanol, 25 to 50 mM added to
cultured pineal glands in vitro, enhanced isoproterenol induced stimulation of
cyclic AMP and melatonin production. Cells were obtained from rats decapitated
during the light phase of a 14 hour light/10 hour dark cycle. The action of
ethanol was observed only at doses of isoproterenol that produced a submaximal
effect, and ethanol alone had no effect on cyclic AMP or melatonin release. The
effects of ethanol on pineal cyclic AMP and melatonin release were reversible
after a 15 min preincubation but not after a 2 hour preincubation.
THE METABOLISM IN VIVO OF
ISOBUTANOL IN RATS LIVER, EVEN IN LOW CONCN, WAS MARKEDLY INHIBITED BY
SIMULTANEOUS OXIDATION OF ETHANOL.
9 HR AFTER TERMINATION OF
DRINKING 3.75 ML OF BEVERAGE CONTAINING 40% ETHANOL IN ORANGE JUICE @ 1.2 G
ETHANOL/KG PLUS 1 G/L ISOBUTANOL, THE CONGENER ALC OR THEIR METABOLITES CAUSED
INCR OF ERROR FIGURES & SUBJECTIVE HANGOVER SYMPTOMS.
ETHANOL (LESS THAN 0.5 MMOLE),
TERT-BUTANOL, & N-PROPANOL INHIBITED N-NITROSODIMETHYLAMINE METABOLISM IN
ISOLATED PERFUSED RAT LIVER.
The effects of prolonged
infusions of ethanol on endothelium dependent vasorelaxation induced by
acetylcholine and adenosine triphosphate (ATP) and on endothelium independent
relaxation induced by papaverine were studied and compared in isolated perfused
male Sprague Dawley rat mesenteric artery preparations. Infusion of ethanol over
60 min at concn of 1.6, 4.7, 6.3, and 7.9 mg/ml caused concn related inhibition
of norepinephrine-induced vasoconstriction. In preparations infused with 6.3 and
7.9 mg/ml, this effect reached a maximum after 10-20 min but had vanished by the
end of the infusion; 1 hr after the end of the infusion, the effects of
norepinephrine were potentiated by 71% and 108%, respectively. Acetylcholine
induced vasorelaxation (EC50 3.0 ng/ml in controls) was significantly reduced
after 6.3 mg/ml ethanol infusion and totally abolished after 7.9 mg/ml ethanol
infusion. ATP induced vasorelaxation (EC50 180 ng/ml in controls) was also
abolished after 7.9 mg/ml of ethanol infusion. By contrast, the vasorelaxant
effects of papaverine were not affected by 7.9 mg/ml ethanol infusion.
Light-microscopic examination revealed that the endothelial cells were present
in ethanol treated and in control mesenteric arterial beds.
Effects of silybin
dihemisuccinate on the ethanol metabolizing systems of the rat liver were
investigated using male Wistar rats. Fifteen min after intoxication with ethanol
(2.0 g, 3.5 g or 5.0 g/kg; ip), the animals were treated with 20 mg, 30 mg or 50
mg/kg of silybin dihemisuccinate (iv via femoral vein), and blood ethanol
concentrations were determined at hourly intervals after ethanol intoxication.
Results showed that silybin dihemisuccinate increased blood ethanol only when
intoxication was produced by doses of 3.5 g and 5.0 g/kg but not by 2 g/kg of
ethanol. This effect is ascribed to an inhibition of the microsomal ethanol
oxidizing system. Activities of alcohol dehydrogenase, catalase and NADPH-dependent
cytochrome c reductase were not affected by silybin dihemisuccinate.
The relationship between
lifetime alcohol (ethanol) consumption and respiratory symptoms in 195 subjects
(including 111 alcoholics) and FEV1 pulmonary function level in 165 subjects
(including 91 alcoholics) was examined. The mean ages for subjects from the
Brockton VA Medical Center were 44.3 yr for pt (in an alcohol treatment program)
and 41.0 yr for employees. Median duration of alcohol consumption was 21 yr, and
the median alcohol consumption was 1527 kg-yr for the pt and was 72 kg-yr for
employees. After adjustment for age and cigarette smoking status, using multiple
logistic regression, lifetime alcohol consumption was a significant predictor of
chronic cough and chronic phlegm, but not of any wheeze or persistent wheeze.
Multiple linear regression analysis indicated that lifetime alcohol consumption
was also a predictor of lower levels of FEV1 in a model that included age,
pack-yr of cigarette smoking, and an interaction between alcohol consumption and
pack-yr. For subjects with both heavy alcohol consumption and smoking, the level
of pulmonary function was higher than expected compared to the effect of smoking
alone.
The present study was
undertaken to isolate and identify specific anatomical structures in the
limbic-midbrain, limbic-forebrain which mediate changes in the ingestion of
alcohol induced by tetrahydropapaveroline. In adult male Sprague Dawley rats, a
23 gauge guide tube was implanted stereotaxically either unilaterally or
bilaterally in cerebral regions extending from coronal planes AP 1.0 to 10.0.
Following recovery, each animal was tested by a standard screen for its
self-selection of water versus an alcohol solution offered in 10 concn increased
on each of 10 days from 3 to 30%. Tetrahydropapaveroline was dissolved in an
artificial CSF vehicle containing Na2S2O5 or ascorbate and then microinjected in
a volume of 1.5 to 2.0 ul at a depth 1.0 to 1.5 mm beneath the tip of the guide.
After a set of 5 microinjections of tetrahydropapaveroline in a dose of 25, 50
or 250 ng was given over 3 days, the same lO day alcohol preference sequence was
repeated. In nearly all rats, the microinjection series was repeated at either
one or two depths 1.0 to 1.5 mm ventral to the first, after which the same
alcohol test was repeated. The results showed that tetrahydropapaveroline
induces or sustains significant incr in alcohol intake when the adduct was
injected at 16 sites within caudal AP planes 1.0 to 5.0. Structures sensitive to
tetrahydropapaveroline included the substantial nigra, reticular formation,
medial lemniscus, zone incerta and medial forebrain bundle. When injected at 21
sites located more rostrally within AP planes 6.5 to 10.0,
tetrahydropapaveroline also evoked significant increments in alcohol intake of a
similar magnitude. The reactive loci included the N. accumbens, olfactory
tubercle, lateral septum, preoptic area, stria terminalis, medial forebrain
bundle and rostral hippocampus. In terms of the efficacy of the dose of
tetrahydropapaveroline microinjected, 25, 50 and 250 ng induced alcohol
self-selection in 81%, 5% and 14% of the sites, respectively. Repeated
microinjections following identical procedures of two control solutions (0.9%
saline or Na2S2O5) at 46 homologous sites within corresponding coronal planes
from AP 1.5 to 10.0 produced no significant alterations in g/kg or proportional
intakes of alcohol. For the rats, the mean intakes of maximally preferred concn
of alcohol in g/kg were 3.83 after caudal injection of tetrahydropapaveroline
(n= 15), 4.36 after rostral injection of tetrahydropapaveroline (n= 20), 0.53
after Na2S2O5 control (n= 18) , and 0.91 after saline control injection (n= 23).
Composite anatomical maps of the tetrahydropapaveroline reactive sites revealed
their integral overlap with dopaminergic pathways which originate in the ventral
tegmentum and substantia nigra and project rostrally to structures within the
limbic forebrain.
Sensitivity to bleomycin
induced chromosome damage in 75 pt (53 men and 22 women) with previously
untreated upper aerodigestive tract malignancies was compared with that in 62
healthy control subjects. Of the pt, 22 (29.3%) had carcinoma of the larynx, 20
(38.7%) had oral cavity lesions, and 23 (30.7%) had pharyngeal malignant tumors.
Data on alcohol use were derived from a questionnaire. 45 pt and 13 controls
were sensitive to bleomycin induced mutagenesis (age breaks/cell > 0.8).
There were site specific differences in the elevated risks associated with
ethanol consumption. The odds ratios for alcohol use were 6.7, 4.3, and 3.3 for
the pharynx, larynx, and oral cavity, respectively. Analysis of alcohol use by
consumption frequency showed incr risks with incr exposure. With the alcohol use
(drinks/day) categories of 0, 1 to 2, 3 to 6, or > 6, the chromosome damage
odds ratios were 1.0, 1.9, 5.0, and 44.5, respectively.
Groups of 10 male Swiss mice
were admin either 2 g/kg ethanol or distilled water ip simultaneously with a
contralateral ip injection of the selective alpha2-adrenoceptor antagonists
atipamezole (1 or 3 mg/kg) or idazoxan (1 or 3 mg/kg), or distilled water. In
expt 2, groups of 8 to 10 Swiss mice were admin ether 2 g/kg ethanol
simultaneously with a contralateral ip injection of either 0.03, 0.1, 1.0 mg/kg
atipamezole or distilled water. In expt 3, mice were admin either 2 g/kg ethanol
or distilled water (ip) at the same time as a contralateral injection of Ro
15-4513 (3 or 10 mg/kg). Ethanol significantly reduced (p < 0.001) core
temperature, while both a2-adrenoceptor antagonists were without effect when
admin alone. However, both the 1 and 3 mg/kg doses of atipamezole significantly
(p < 0.05) attenuated the ethanol induced reduction in body temperature 20
and 40 min after admin. The 3 mg/kg dose of idazoxan (but not the 1 mg/kg dose)
also significantly (p < 0.05) attenuated ethanol's hypothermic effect 20 min
after admin but this effect was not statistically significant at 40 min. In expt
2, using lower doses of atipamezole, attenuation of ethanol-induced hypothermia
caused by atipamezole was found to be dose related. The benzodiazepine inverse
agonist Ro 15-4513 possessed an intrinsic hypothermic action (p < 0.001) but
neither attenuated nor enhanced the hypothermic effect of ethanol.
The effects of 6 wk of heavy
ethanol (liquid diet of 36% ethanol) and moderate ethanol (liquid diet of 3.6%
ethanol) feeding to male Wistar rats upon lipids and lipoprotein metabolism were
determined. As compared to the control group (rats fed isocaloric amounts of
dextrimaltose in place of ethanol), the heavy ethanol feeding resulted in the
following changes: liver wt/kg body wt incr by 48% with a concomitant 52% incr
in liver protein/kg body wt and a 2.75-fold incr in liver total lipids/kg body
wt. In contrast, liver DNA/kg body wt or per liver was not affected
significantly. Plasma cholesterol and triglycerides were higher by 53% and 77%,
respectively. Liver cholesterol and triglycerides were 4.4-fold and 3.8-fold
higher, respectively. Plasma total A1 was 1.72-fold higher 0.001), whereas there
was no significant difference in plasma apo E levels between the two groups.
However, plasma high density lipoproteins (HDL) apo E was 48% lower while the
very low density lipoproteins (VLDL) E was 2.15-fold higher. Hepatic total
protein synthetic rate in the ethanol group was not significantly different from
the control group. In contrast, labeled leucine incorporation into the total
secretory proteins was inhibited by 36% in the ethanol fed group. Specifically,
inhibitions of the synthetic rates of various secretory proteins in the ethanol
group compared to the control group were as follows: by 55% for total VLDL
apoproteins, by 44% for apo A1 protein, by 55% for total apo E proteins, by 62%
for VLDL apo E, by 52% for HDL apo E and by 50% for transferrin. In contrast,
moderate ethanol feeding for six wk did not alter any of the above parameters.
The modifying effect of
ethanol on aflatoxin B1 (AFB1)-induced hepatocarcinogenesis was examined in male
ACI/N rats by chronic treatment at the post initiation phase. Rats received an
ip injection of AFB1 (1.5 mg/kg) twice a wk for 10 wk (a total of 20 doses).
Following a wk of acclimation, they were given 10% ethanol as drinking water for
56 wk. The effects of ethanol on hepatocarcinogenesis were evaluated in terms of
the incidence of altered hepatocellular foci and neoplasms at the end of the
experiment. Exposure to AFB1 alone induced a substantial number of altered foci
(6.98 iron excluding foci/sq m) in rats. The number of altered liver cell foci
in rats receiving AFB1 followed by ethanol was significantly incr (26.39 iron
excluding foci/sq cm). In the rats given ethanol after AFB1, the total area and
mean diameter of both iron excluding foci and altered foci identified in
hematoxylin and eosin-stained sections were significantly higher than in the
rats exposed to AFB1 alone. The incidence of liver cell tumors of the group
given AFB1 and ethanol (3/15, 20%) was higher than that of the group treated
with AFB1 alone (0/14, 0%). Treatment with ethanol alone for 56 wk did not
induce either.
The effect of nicotine and
nicotine/ethanol were examined using a 4-hr perfused human placental system and
human placental vesicles. Placental systems and vesicles from nonsmokers were
exposed to 'physiological' (0.2 uM) and large (about 20 uM) nicotine concn
alone, as well as nicotine combined with 200 or 400 mg/ml ethanol, for 5 min, 24
hr, and 48 hr. Two nonmetabolizable amino acids, alpha-aminoisobutyric acid and
cycloleucine were used as probes. The maternal compartment half-life of nicotine
was 2.12 hr without ethanol and 2.65 hr with addition of ethanol. There was no
statistically significant evidence of decr transport of these amino acids with
exposure in either test system. There was no evidence of altered transport of
antipyrine, nonspecific leakage of water or difference in lactate output, or
glucose consumption with exposure of the perfused placenta to either nicotine or
nicotine/ethanol.
Groups of 6 to 12 male CD-1
mice were given an ip injection of the anticonvulsive drug carbamazepine (10,
15, or 20 mg/kg) or propylene glycol (vehicle) 10 min before ip admin of 1.0,
1.5, 2.0, 2.5, or 4.0 g/kg ethanol in saline. Whereas mice that received 1.5
g/kg ethanol regained their normal motor coordination within 45 min of ethanol
admin, only 85 and 75% of normal motor coordination was recorded in mice
injected with 2 and 2.5 g/kg ethanol respectively, at 60 min post-ethanol.
Carbamazepine significantly potentiated the motor incoordinating effect of 2
g/kg ethanol in a dose-dependent fashion. Motor coordination was only 35 and 20%
of normal at 15 and 20 mg/kg carbamazepine, even at 60 min post-ethanol.
Although carbamazepine did not alter the onset time, it significantly prolonged
the duration of ethanol induced loss-of-righting reflex. 15 mg/kg carbamazepine
significantly prolonged the duration of loss-of-righting reflex produced by 4
g/kg ethanol (hypnotic dose), compared to the saline + ethanol group, 102 vs
38.0 min, respectively. Pretreatment with theophylline (25 and 50 mg/kg)
significantly attenuated the carbamazepine induced potentiation of both effects.
50 mg/kg theophylline markedly attenuated the potentiation on ethanol induced
motor incoordination by carbamazepine (15 and 20 mg/kg) at all post-ethanol time
periods. Results from a blood ethanol study indicated no effect of carbamazepine
on the clearance of ethanol.
In Sprague-Dawley rats having
relatively little experience in the open field, the actions of ethanol (0.75
g/kg ip), Ro15-4513, an imidazobenzodiazepine partial inverse antagonist, (1.25
mg/kg and 2.5 mg/kg, ip), and Ro15-4513 in combination with ethanol were
measured on horizontal activity. Rats receiving ethanol showed a significant
depression in horizontal activity. Doses of Ro15-4513 given alone (n = 14)
produced no significant differences in activity from baseline levels. Rats (n =
8) pretreated with Ro15-4513 prior to receiving ethanol, however, showed a
significant attenuation of the ethanol induced depression of activity.
The interactions of cocaine
with ethanol in nontolerant and ethanol-hypnosis tolerant male Sprague-Dawley
rats were examined. Cocaine pellets (12.5 mg) implanted sc in rats potentiated
the hypnosis induced by ethanol (3.2 g/kg ip) and the implantation of the same
type of pellets (12.5, 25 mg) in ethanol tolerant rats restored the ethanol
hypnosis to levels observed in acutely treated animals.
Serotonin-stimulated
activation of phospholipase C in primary astroglial cell cultures made from
newborn Sprague-Dawley rats was studied as a mean of evaluating the effect of
acute ethanol exposure on this signal transduction system. The addition of
50-150 mM ethanol prior to stimulation with 10-5 M serotonin led to a
potentiation of the serotonin-induced (3H)-inositol phosphate formation and an
incr incorporation of (3H)-inositol into the three phosphoinositides studied.
The potentiating effect of ethanol was observed only when ethanol was added
together with serotonin. Ethanol had no effect on arginine-vasopressin,
bradykinin or phenylephrine-stimulated inositol lipid metabolism.
The effects of cadmium (100
ppm through drinking water) and ethanol (5 g/kg by gastric gavage)
administration on biogenic amines, metal distribution and certain enzymes in
male Wistar rat brain was investigated after 90 days of exposure. Co-exposure
group revealed significant accumulation of cadmium and also incr in zinc levels
compared to all the other groups. Ethanol alone decr monoamine oxidase activity
and incr norepinephrine and 5-hydroxytryptamine levels, while in combination
with Cd, these effects were more magnified.
Male CD-1 mice were given a
series of tones paired with footshock in the closed arm of a Y maze. On a test
session 8 days later the animals were tested for retention of the conditioned
emotional response (CER). On the 2-min test session, the three arms of the maze
were open and the number of entries into the arms was counted. Retention of the
conditioned emotional response was measured by the decr in the number of entries
in comparison with mice trained with no footshock. Starting 24 hr after
training, and continuing for the 7 days between training and testing, the
animals in different groups received a daily ip injection of saline, 3.6 g/kg of
ethanol, 150 ug/kg of the cholinergic muscarinic agonist oxotremorine, or
ethanol plus oxotremorine. Retention was evaluated 24 hr after the last
injection. Ethanol reduced retention of the conditioned emotional response. This
effect was attenuated by oxotremorine (150 ug/kg) given ip 6 min prior to
testing, but not by the same dose of oxotremorine given daily together with the
ethanol treatment. Oxotremorine injections administered prior to the retention
test also enhanced the retention performance of the control group. Daily
oxotremorine administration had no effect.
The effects of methyl n-butyl
ketone (2.5, 3.75, and 5.0 mmol/kg ip), methyl isobutyl ketone (2.5 and 5 mmol/kg
ip), methyl ethyl ketone (5, 10, and 15 mmol/kg ip) and acetone (10, 20, and 40
mmol/kg ip) on the duration of ethanol-induced loss of righting reflex and on
ethanol elimination in male CD-1 mice were studied. The solvents were dissolved
in corn oil and injected ip 30 min before ethanol 4 g/kg ip. The 4 solvents
prolonged significantly the duration of ethanol induced loss of righting reflex
when given in the following doses (mmol/kg): methyl n-butyl ketone, 3.75 and 5
(mean time = 11.5 min); methyl isobutyl ketone, 5: methyl ethyl ketone, 5 and
10, acetone, 20 and 40. This prolongation was dose related and increased as the
dose of the solvent was increased. A dose of 40 mmol/kg acetone resulted in
ataxia in all mice treated with this dose. The concn of ethanol in blood or
brain (approx 2.5 to 3.5 mg/ml or mg/g, respectively) on return of the righting
reflex were similar in solvent treated and control animals, with the exception
of the group of mice treated with 40 mmol/kg acetone in which the ethanol concn
were significantly lower than in control animals. The mean elimination rate of
ethanol was markedly reduced (from 692 mg/hr/kg for controls) in mice treated
with methyl n-butyl ketone 5 mmol/kg (523 mg/hr/kg), methyl ethyl ketone 15 mmol/kg
(575 mg/hr/kg), and acetone 40 mmol/kg (386 mg/hr/kg). All 4 solvents reduced
the activity of mouse liver alcohol dehydrogenase in vitro. The admin of 2,5
hexanedione (0.75 mmol/kg ip) did not alter the duration of ethanol induced loss
of righting reflex, nor did it affect the concn of ethanol in the blood or brain
on return of the righting reflex. Admin of 2-hexanol (2.5 mmol/kg ip)
significantly prolonged the duration of ethanol induced loss of righting reflex
but did not affect ethanol concn in the blood or brain on return of the righting
reflex.
To determine whether or not
the previously reported association between alcohol (ethanol) intake and high
blood pressure is influenced by differential intake of calcium and potassium in
drinkers compared with nondrinkers and to assess the magnitude of the
independent contributions of alcohol, calcium, and potassium to blood pressure,
these associations were evaluated in 7,011 men of Japanese descent. Alcohol
consumption above a threshold of approx 20 ml/day was found to be positively,
strongly, and independently correlated with systolic and diastolic pressures,
and this effect was completely independent of the effects of calcium and
potassium. Calcium and potassium intake were highly correlated and were
inversely related to blood pressure, and their combined effect was greater than
the effect of either alone. However, in the subgroup of moderate and heavier
drinkers, only potassium was inversely related to blood pressure. This finding
is compatible with previous reports of malabsorption and incr excretion of
calcium at higher levels of alcohol intake, and it indicates that a small
portion of the alcohol-induced blood pressure elevation may be mediated through
calcium depletion. In the range of dietary intake in this cohort, the effect of
alcohol on blood pressure was stronger than was either the separate or combined
effects of calcium and potassium.
Groups of 8 male albino rats
were given water ad lib and assigned to one of the following treatments, 6
days/wk for 4 mo: (Group 1) no treatment (control); (Groups 2 to 4) 1, 2, and 5
g/kg ethanol, once by gastric gavage; (Group 5) lead as lead acetate, 0.55 g/l
in drinking water; (Groups 6 to 8) 1, 2, and 5 g/kg ethanol, once by gastric
gavage plus lead as 0.55 g/l lead acetate in drinking water. Ethanol or lead
when given alone inhibited the activity of blood gamma-aminolevulinic acid
dehydratase (p < 0.05 compared to control for all levels after 2 mo
treatment). Ethanol caused a dose-dependent incr in hepatic lipid peroxidation,
which was more marked after 4 mo co-exposure to lead and ethanol. The
co-administration of 5 but not 1 or 2 g/kg ethanol significantly enhanced the
lead-induced inhibition of blood gamma-aminolevulinic acid dehydratase activity
and the elevation of gamma-aminolevulinic acid excretion (p < 0.05). Exposure
to lead and ethanol (5 g/kg) produced a more pronounced incr in hepatic lipid
peroxidation and blood glucose level than either ethanol or lead alone.
Co-exposure to ethanol did not affect the lead-induced incr in blood zinc
protoporphyrin except at 5 g/kg after 4 mo exposure, when the level was
significantly higher than in the lead group (p < 0.05). This combination also
caused a significant incr in the dopamine contents of striatum, midbrain and
pons medulla, norepinephrine contents in midbrain and 5-hydroxytryptamine
contents of hypothalamus, striatum, midbrain and pons medulla over levels
produced by lead alone. However, the level of norepinephrine in hypothalamus
decr upon co-administration. The uptake and retention of lead was significantly
(p < 0.05) higher in blood, liver, kidney and brain in animals co-exposed to
lead and 5 g/kg ethanol. Blood and kidney lead was also increased by 2 g/kg
ethanol (p < 0.05).
The effects of ethanol on
releasable Ca stores were examined in microsomes isolated from ICR mouse whole
brains. Ca release was monitored by detn of changes in the extra-microsomal Ca
concn using Indo-1, a fluorescent Ca indicator. In the absence of ATP, ethanol
released Ca from microsomes in a concn dependent manner, with a threshold for Ca
release between 25 and 50 mM. A 50 mM concn of ethanol released about 0.5 nmol
of Ca per mg of microsomal protein. The highest concn of ethanol (400 mM)
released approx 5 nmol Ca/mg microsomal protein. Release was maximal within 10
sec. Ethanol induced release of microsomal Ca was reduced by approx 50% after
ATP stimulated uptake of Ca, indicating that the ethanol releasable pool was
diminished by ATP dependent uptake of Ca into an ethanol insensitive microsomal
pool. Release of Ca produced by ethanol was linear with concn (25 to 400 mM). Ca
release induced by ethanol was not altered by incr the temp from 15 to 25 C.
However, incr the temp from 25 to 32 C and from 32 to 36 C produced a large incr
in the ability of ethanol to release Ca. Simultaneous addition of ethanol and
inositol 1,4,5-triphosphate produced additive responses.
Intranasal cocaine and oral
ethanol (ETOH) were admin to nine male subjects (21-45 yr) during daily exptl
sessions. In 3 hr sessions (5 days), a 14 min period of resting baseline was
followed by the exptl session which consisted of 10 min of task performance,
admin of ETOH (0, 19.4, 38.7, or 58.1 g), 35 min of ETOH baseline, admin of
cocaine HCl (4, 48, 96 mg), 20 min of ETOH and intranasal cocaine baseline, 10
min of task performance, 40 min of resting, 10 min of task performance, and 6
min of resting. Intranasal cocaine increased resting heart rate and blood
pressure, and oral ETOH increased resting heart rate and decreased resting blood
pressure.
Drug Tolerance:
CROSS TOLERANCE BETWEEN
ALCOHOL & OTHER DRUGS MAY BE DUE TO PHARMACODYNAMIC TOLERANCE IN THE CNS OR
TO MORE RAPID METABOLISM, SINCE THE USE OF ALCOHOL INCR HEPATIC MICROSOMAL
ENZYME ACTIVITY.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Ethanol will enter the
environment as emissions from its manufacture, use as a solvent and chemical
intermediate, and release in fermentation and alcoholic beverage preparation. It
naturally occurs as a plant volatile, microbial degradation product of animal
wastes, and in natural fermentation of carbohydrates. When spilled on land it is
apt to volatilize, biodegrade, and leach into the ground water, but no data on
the rates of these processes could be found. Its fate in ground water is
unknown. When released into water it will volatilize and probably biodegrade. It
would not be expected to adsorb to sediment or bioconcentrate in fish. Although
no data on its biodegradation in natural waters could be found, laboratory tests
suggest that it may readily biodegrade and its detection in water systems may be
due in part to its extensive use in industry with possible relatively steady and
large levels of discharges. When released to the atmosphere it will photodegrade
in hours (polluted urban atmosphere) to an estimated range of 4 to 6 days in
less polluted areas. Rainout should be significant. Human exposure will be
primarily in occupational atmospheres and consumption of products containing
ethanol. Exposure will also occur from other contaminated atmospheres especially
in proximity to industries and cities, and ingestion of contaminated drinking
water, as well as proximity to sources of natural release(SRC).
Probable Routes of Human Exposure:
Humans will be exposed to
ethanol by ingestion of foods, flavorings, beverages, and pharmaceuticals (SRC).
Workers will be exposed to ethanol in occupational settings associated with its
manufacture, use as a solvent or use in synthesis(1), or when released as a
product of fermentation, decomposition or combustion (including cigarette
smoke)(2).
Inhalation of vapor and
percutaneous absorption ... eye and skin contact.
NIOSH (NOHS Survey 1972-1974)
has statistically estimated that 3,240,470 workers are exposed to ethanol in the
USA(1). Finnish furniture factory, 1975-84, 394 samples, 70% pos, 32 ppm avg of
pos(2).
There is probably greater
exposure to ethanol than to any other solvent with the exception of water. Not
only is it used as a solvent in industry, but it is heavily consumed by large
numbers of people as a component of potentially intoxicating beverages. As a
result of the petroleum shortage, plans call for diluting gasoline with ethanol
to form a combustible product termed "gasohol". At that point it is
likely that ... /there will be/ universal exposure to ethanol.
Natural Pollution Sources:
Emissions from animal wastes,
plants, insects, forest fires, microbes, and volcanoes(1). Emissions from
natural fermentation of carbohydrates(2).
Artificial Pollution Sources:
Emissions from petroleum
manufacture and storage, plastics, printing, refuse combustion, tobacco smoke,
wood pulping, and whiskey manufacture(1). Leachate from landfills(2). Emissions
and wastewater from its manufacture and use as a solvent and chemical
intermediate(SRC,3).
In gasoline exhaust: 0.1 to
0.6 ppm; in workrooms: concn up to 5000 ppm have been reported; from whiskey
fermentation vats: avg 182.2 g/cu m grain input
Environmental Fate:
TERRESTRIAL FATE: When spilled
on soil, ethanol will both evaporate and leach into the ground due to the
relatively high vapor pressure and low adsorption in soil. It will biodegrade in
soil, probably to acetic acid and formaldehyde(1). If degradation is not rapid,
it will leach into groundwater(SRC).
AQUATIC FATE: When released
into water, ethanol will volatilize (estimated half life is 6 days) and
biodegrade. It will not sorb to sediment or bioconcentrate in aquatic organisms.
Although it readily biodegrades in laboratory tests, no data on its rate of
degradation in natural waters could be found(SRC).
ATMOSPHERIC FATE: When
released into the atmosphere, ethanol will photodegrade with a half-life ranging
from hours in polluted urban atmospheres to approximately 6 days in cleaner
atmospheres (based on a hydroxyl radical concn of 8X10+6 moles/cu cm). Due to
its solubility in water, rainout may be an important process(SRC).
Environmental Biodegradation:
Ethanol is biodegraded in
aerobic systems using activated sludge, sewage (including filtered and settled),
wastewater and soil inoculums(1-6). 5 day theoretical BOD values range from 37%
- 86%(1,4). Biodegradation of 3, 7, and 10 mg/l with filtered sewage seed in
fresh water resulted in 74% theoretical BOD in 5 days and 84% in 20 days; in
salt water 45% theoretical BOD in 5 days and 75% in 20 days were observed(4).
Formaldehyde and acetic acid are products of biodegradation by a soil
inoculum(6). Anaerobic degradation (thermophilic digestion, 54 deg C) of ethanol
(5 ml of a 5% aqueous ethanol solution) produced approx 1000 ml gas/g sample
using seed which had been prepared in a synthetic medium(7).
Environmental Abiotic Degradation:
The estimated half-life of
ethanol in the atmosphere ranges from 5.9 days(1) to 4 days (based on a hydroxyl
radical concentration of 0.8X10+6 molec/cu cm(2,9)). The half-life for ethanol
in hydrogen peroxide/nitrite/carbon monoxide mixtures (total pressure 100 torr;
typical sunlit atmosphere) is 10 hrs at 19 degrees C(3). Photochemical smog
chamber tests with 500 ppm ethanol and 500 ppm nitrite, sulfide, and/or water
resulted in varying amounts of degradation: 50% degradation in 0.7 hr
(nitrite/sulfide/water), 50% in 2.8hr (nitrite) and 25% in 6.3hr (sulfide)(5). A
smog chamber test with 2 ppm ethanol and 1 ppm nitrogen resulted in 20%
degradation in 5 hr(4). Ethanol is considered to have low reactivity (class 2 in
a 5 class system (5 high)) in photochemical smog situations having ozone forming
potential slightly higher than that of toluene(6). Reaction with hydroxyl
radicals in aquatic media will not likely be a significant process(7,8).
Alcohols are known to be resistant to hydrolysis(9).
Environmental Bioconcentration:
No information on the
bioconcentration factor for ethanol could be found in the literature. However,
its low octanol/water partition coefficient (log P -0.31; recommended value(1))
indicates that it will not bioconcentrate in fish(SRC).
Soil Adsorption/Mobility:
No information on the
adsorption of ethanol could be found in the literature. Its low octanol/water
partition coefficient (log P -0.31; recommended value(1)) indicates that its
adsorption to soil will be low(SRC).
Volatilization from Water/Soil:
The estimated half life for
evaporation of ethanol from water 1m deep with a 1m/sec current and 3m/sec wind
is 6.1 days and the gas exchange rate plays a more dominant role than the liquid
exchange rate(1,SRC) based on the non dimensional Henry constant(0.257x10(-3)
(2)). Ethanol is relatively volatile (vapor pressure 50 torr(3)) and would,
therefore, readily evaporate from soil at the soil/air interface and solid
surfaces(SRC).
Environmental Water Concentrations:
DRINKING WATER: Detected (not
quantified) in 5 city public supplies(1); detected (not quantified) in city
public supplies(2-4). Philadelphia (1975-1976), identified, not quantified, in 1
of 3 water treatment plants and in drinking water of 1 of 1 hotel(5).
GROUNDWATER: Ethanol was found
in groundwater suspected of leachate contamination (based on levels of
inorganics) 190 ppb (1/13 sites pos), and detected at 58 ppb in landfill
groundwater where inorganic levels indicated good or unknown water quality(2).
Not detected in Miami, FL(1).
SURFACE WATER: Detected (not
quantified) in 4 raw water sources - uncontaminated and contaminated with
agricultural runoff, municipal or industrial wastes(1); Hayashida River (Jpn)
highly polluted by leather industry, 4020 ppb(2). Detected at 58 ppb in landfill
groundwater where inorganic levels indicated good or unknown water quality(3).
RAIN/SNOW: Santa Rita, AZ
(rural), concn in precipitation, 15 ppb (by mass), ratio of concn in
precipitation/condensate 0.31(1).
Effluent Concentrations:
Ethanol was detected in
leachate from Minnesota landfills in the range of 23,000 ppb to 110,000 ppb (2/6
sites pos)(1). Traces found in 1 of 11 domestic wells near Granby, CT landfill,
1984(2). Concn in exhaust from simple hydrocarbon fuels (e.g. benzene,
isooctane) <0.1-0.6 ppm(3).
Atmospheric Concentrations:
RURAL/REMOTE: Pt. Barrow, AK,
1967, 24 hr avg is 0.77 ppb (upper limit methanol has same retention time; 17 of
25 samples pos)(1). URBAN: Chicago, IL: detected near 9% and in 46% homes tested
(min 0.5 ppb; max <100 ppb)(2). Urban: Leningrad, USSR 1976 - detected not
quantified(3). Air pollution peak: Japan 29-57 ppb(4). Concn mean atmospheric
(ppb by mass/volume): Tuscon, AZ, Feb-Sept 1982, 3.3 ppb (17 samples each);
Santa Rita and Mt. Lemmon (rural), but influenced by anthropogenic contamination
from the greater Tucson metropolitan area Aug-Sept 1982, 0.40 ppb (18 samples
each)(5).
... In workrooms: concn up to
5000 ppm have been reported ... .
Food Survey Values:
Identified, not quantified, as
a volatile plant isolate in soy beans(1). Present at various concn in many
beverages(2). Concn (ppb) in lima, common, mung, and soy beans (7, 5, 1 and 1
samples respectively): 1500-7900, 4200 avg; split peas, 3600; lentils 4400(3).
Identified, not quantified, as a volatile flavor component in fried bacon(4) and
mountain Beaufort cheese (French Alps, summer and winter)(5).
It is ... present to extent of
3-6% by vol in naturally fermented beers and ales, 10-12% in wines and 20-60% in
distilled beverages.
Environmental Standards & Regulations:
FIFRA Requirements:
Unless designated as an active
ingredient /as determined by EPA/, this substance, when used in antimicrobial
products as a solvent (except in textures or where sole or major active
ingredients) is considered inert, having no independent pesticidal activity. The
percentage of such an ingredient shall be included on the label in the total
percentage of inert ingredients.
Residues of ethyl alcohol are
exempted from the requirement of a tolerance when used as a solvent or cosolvent
in accordance with good agricultural practices as inert (or occasionally active)
ingredients in pesticide formulations applied to growing crops or to raw
agricultural commodities after harvest.
Ethyl alcohol is exempted from
the requirement of a tolerance when used as a solvent or cosolvent in accordance
with good agricultural practice as inert (or occasionally active) ingredients in
pesticide formulations applied to animals.
Atmospheric Standards:
This action promulgates
standards of performance for equipment leaks of Volatile Organic Compounds (VOC)
in the Synthetic Organic Chemical Manufacturing Industry (SOCMI). The intended
effect of these standards is to require all newly constructed, modified, and
reconstructed SOCMI process units to use the best demonstrated system of
continuous emission reduction for equipment leaks of VOC, considering costs, non
air quality health and environmental impact and energy requirements. Ethanol is
produced, as an intermediate or final product, by process units covered under
this subpart.
FDA Requirements:
Substance added directly to
human food affirmed as generally recognized as safe (GRAS).
Ethanol is an indirect food
additive for use only as a component of adhesives.
Allowable Tolerances:
Residues of ethyl alcohol are
exempted from the requirement of a tolerance when used as a solvent or cosolvent
in accordance with good agricultural practices as inert (or occasionally active)
ingredients in pesticide formulations applied to growing crops or to raw
agricultural commodities after harvest.
Ethyl alcohol is exempted from
the requirement of a tolerance when used as a solvent or cosolvent in accordance
with good agricultural practice as inert (or occasionally active) ingredients in
pesticide formulations applied to animals.
Chemical/Physical Properties:
Molecular Formula:
C2-H6-O
Molecular Weight:
46.07
Color/Form:
CLEAR, COLORLESS, VERY MOBILE
LIQUID
Clear, colorless liquid.
Odor:
Mild, rather pleasant; like
wine or whiskey
Weak, ethereal, vinous odor.
Taste:
Burning
Boiling Point:
78.5 DEG C
Melting Point:
-114.1 DEG C
Critical Temperature & Pressure:
CRITICAL TEMPERATURE: 243 DEG
C; CRITICAL PRESSURE: 63 ATM
Density/Specific Gravity:
0.789 @ 20 DEG C/4 DEG C
Dissociation Constants:
pKa = 15.9 at 25 deg C
Heat of Combustion:
326.68 kg cal/g mol wt at 25
deg C
Heat of Vaporization:
9673.9 G CAL/G MOLE
Octanol/Water Partition Coefficient:
log Kow= -0.31
Solubilities:
> 10% in water
> 10% in ether
> 10% in acetone
> 10% in benzene
MISCIBLE WITH WATER & MANY
ORG SOLVENTS
Water solubility = miscible
Spectral Properties:
INDEX OF REFRACTION: 1.361 @
20 DEG C/D
MAX ABSORPTION (GAS): 181 NM
(LOG E= 2.51); SADTLER REFERENCE NUMBER: 188 (IR, PRISM); 64 (IR, GRATING)
IR: 6986 (Coblentz Society
Spectral Collection)
NMR: 14 (Varian Associates NMR
Spectra Catalogue)
MASS: 16 (Atlas of Mass
Spectral Data, John Wiley & Sons, New York)
Intense mass spectral peaks:
31 m/z , 45 m/z, 46 m/z
Surface Tension:
22.75 dynes/cm in contact with
vapor @ 20 deg C
Vapor Density:
1.59 (AIR= 1)
Vapor Pressure:
59.3 mm Hg at 25 deg C /from
experimentally derived coefficients/
Viscosity:
44.0 CP -98.11 deg C; 1.773 CP
at 0 deg C; 1.200 CP at 20 deg C; 0.504 CP at 70 deg C
Other Chemical/Physical Properties:
% IN SATURATED AIR: 6.58 @ 25
DEG C; DENSITY OF SATURATED AIR: 1.04 (AIR= 1); EQUIVALENCES: 1 MG/L= 532 PPM; 1
PPM= 1.88 MG/CU M @ 25 DEG C & 760 MM HG
RATIO OF SPECIFIC HEATS OF
VAPOR: 1.128; HEAT OF SOLUTION: -55 CAL/G= -2.3X10+5 J/KG= -99 BTU/LB; REID
VAPOR PRESSURE: 2.3 PSIA
Specific heat 0.618 cal/g @ 23
deg C
Heat of Formation: -66.37
kcal/mol (liq); -56.19 kcal/mol (gas) at 25 deg C
Heat of Fusion: 26.05 cal/g=
108.99 J/g= 5,021 J/mol
Absorbs water rapidly
SOLIDIFIES BELOW -130 DEG C
Heat capacity: 113.0 J/mol-K
(liquid) & 65.7 J/mol-K (gas) at 25 deg C & 1 atm
VOLATILE
Dielectric constant: 25.00 at
20 deg C; 20.21 at 55 deg C; dipole moment: 1.69 (gas), 1.71 in benzene at 25
deg C
Enthalpies of formation:
-66.20 kcal/mole (liquid); -56.03 kcal/mole (gas); Gibbs (free) energies of
formation: -41.63 kcal/mole (liquid); -40.13 kcal/mole (gas); Entropies: 38.49
cal/deg-mole (liquid); 67.54 cal/deg-mole (gas); Heat capacities: 26.76
cal/deg-mole (liquid); 15.64 cal/deg-mole (gas)
Heat of melting: 1.198
kcal/mole; heat of sublimation: 10.11 kcal/mole at 298 K; specific heat: 19.36
cal/K.mol at 400 K
Observed and estimated
solubility of naphthalene in ethanol at 40 deg C: 0.073 mole fraction (observed)
& 0.054 mole fraction (estimated)
Observed and estimated
solubility of anthracene in ethanol at 20 deg C: 0.0005 mole fraction (observed)
& 0.0004 mole fraction (estimated)
Observed and estimated
solubility of phenanthrene in ethanol at 20 deg C: 0.0123 mole fraction
(observed) & 0.0102 mole fraction (estimated)
Rate constant for reaction of
ethanol with OH radical at 300 K: 1.8X10+12 cu cm/mol-sec
Electrical conductivity:
1.35X10-9/ohm cm at 25 deg C; heat of solution: 2.54 kcal/mole solute in water
at 13 deg C; latent heat of fusion: 24.9 cal/g; specific tension: 22.1 dynes/cm
at 25 deg C; wt/gal: 6.61 at 20 deg C
Forms binary azeotropes with
tert-amyl ethyl ether, benzene, 1-bromobutane, 2-bromobutane,
cis-1-bromo-1-butene, trans-1-bromo-1-butene, cis-2-bromo-2-butene,
trans-2-bromo-2-butene, 2-bromo-1-butene, 1-bromo-3-methylbutane,
1-bromo-1-methylpropane, 2-bromo-2-methylpropane, 1-bromopropane,
2-bromopropane, 2-bromopropane, trans-1-bromopropene, cis-1-bromopropene, tert-butyl
ethyl ether, carbon disulfide, carbon tetrachloride, 1-chlorobutane,
2-chlorobutane, cis-1-chloro-1-butene, trans-1-chloro-1-butene,
2-chloro-1-butene, cis-2-chloro-2-butene, chloroform, 1-chloro-3-methylbutane,
1-chloro-2-methylpropane, 1-chloropropane, 2-chloropane, trans-1-chloropropene,
3-chloropropene, 1,3-cyclohexadiene, cyclohexane, cyclohexane, cyclopentane,
1,1-dichloropropane, 2,2-dichloropropane, 2,5-dimethylhexane, diethoxymethane,
ethyl acetate, ethyl acrylate, ethyl propionate, ethyl propyl ether, ethyl
sulfide, fluorobenzene, n-heptane, n-hexane, 2-iodobutane,
1-iodo-2-methylpropane, 1-iodopropane, 2-iodopropane, 3-iodopropene, isobutyl
formate, isoprene, isopropyl acetate, methyl acetate, methyl acrylate, methyl
borate, 2-methylbutane, methyl butyrate, methyl carbonate, methylcyclopentene,
methylcyclopentene, methyl ethyl ketone, methyl propionate, octane, pentane,
2-pentanone, perchloroethylene, propanediol, propyl acetate, propyl ether,
thiophene, toluene, trichloroethylene
Forms ternary azeotropes with
water, acetal; water, benzene; water, bromodichlormethane; water,
1-bromo-2-methylpropane; water, cis-1-bromopropane; water, trans-bromopropane;
water, 1-bromopropane; water, 2-bromopropane; water, carbon disulfide; water,
chloroform; water, 1-chloro-2-methylpropane; water, cyclohexene; water,
1,2-dichloroethane; water, cis-1,2-dichloroethylene; water,
trans-1,2-dichloroethylene; water, dimethoxymethane; water, ethyl acetate;
water, ethyl chloroacetate; water, trichloroethylene; water, triethylamine
Saturated concn in air: 105
g/cu m at 20 deg C, 182 g/cu m at 30 deg C
Liquid heat capacity: 0.583
BTU/lb-F @ 70 deg F; Liquid thermal conductivity: 1.159 BTU-in/hr-sq ft-F at 70
deg F; Saturated vapor density: 0.00716 lb/cu ft @ 70 deg F; Ideal gas heat
capacity: 0.384 BTU/lb-F @ 75 deg F
Diffusion coefficient: 0.034
sq m/hr (calculated) & 0.037 sq m/hr (experiment) in air at 0 deg C and 1
atm
Magnetic susceptibility:
0.734X10-6 at 20 deg C
VAPOR PRESSURE= 40 MM HG @ 19
DEG C
Henry's Law constant = 5X10-6
atm-cu m/mol at 25 deg C
Chemical Safety & Handling:
DOT Emergency Guidelines:
Fire or explosion: HIGHLY
FLAMMABLE: Will be easily ignited by heat, sparks or flames. Vapors may form
explosive mixtures with air. Vapors may travel to source of ignition and flash
back. Most vapors are heavier than air. They will spread along ground and
collect in low or confined areas (sewers, basements, tanks). Vapor explosion
hazard indoors, outdoors or in sewers. Some may polymerize (P) explosively when
heated or involved in a fire. Runoff to sewer may create fire or explosion
hazard. Containers may explode when heated. Many liquids are lighter than water.
/Ethanol; Ethanol, solution/
Health: Inhalation or contact
with material may irritate or burn skin and eyes. Fire may produce irritating,
corrosive and/or toxic gases. Vapors may cause dizziness or suffocation. Runoff
from fire control may cause pollution. /Ethanol; Ethanol, solution/
Public safety: CALL Emergency
Response Telephone Number on Shipping Paper first. If Shipping Paper not
available or no answer, refer to appropriate telephone number listed on the
inside back cover. Isolate spill or leak area immediately for at least 25 to 50
meters (80 to 160 feet) in all directions. Keep unauthorized personnel away.
Stay upwind. Keep out of low areas. Ventilate closed spaces before entering.
/Ethanol; Ethanol, solution/
Protective clothing: Wear
positive pressure self-contained breathing apparatus (SCBA). Structural
firefighters' protective clothing will only provide limited protection.
/Ethanol; Ethanol, solution/
Evacuation: Large spill:
Consider initial downwind evacuation for at least 300 meters (1000 feet). Fire:
If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters
(1/2 mile) in all directions; also, consider initial evacuation for 800 meters
(1/2 mile) in all directions. /Ethanol; Ethanol, solution/
Fire: CAUTION: All these
products have a very low flash point: Use of water spray when fighting fire may
be inefficient. Small fires: Dry chemical, CO2, water spray or alcohol-resistant
foam. Large fires: Water spray, fog or alcohol-resistant foam. Do not use
straight streams. Move containers from fire area if you can do it without risk.
Fire involving tanks or car/trailer loads: Fight fire from maximum distance or
use unmanned hose holders or monitor nozzles. Cool containers with flooding
quantities of water until well after fire is out. Withdraw immediately in case
of rising sound from venting safety devices or discoloration of tank. ALWAYS
stay away from the ends of tanks. For massive fire, use unmanned hose holders or
monitor nozzles; if this is impossible, withdraw from area and let fire burn.
/Ethanol; Ethanol, solution/
Spill or leak: ELIMINATE all
ignition sources (no smoking, flares, sparks or flames in immediate area). All
equipment used when handling the product must be grounded. Do not touch or walk
through spilled material. Stop leak if you can do it without risk. Prevent entry
into waterways, sewers, basements or confined areas. A vapor suppressing foam
may be used to reduce vapors. Absorb or cover with dry earth, sand or other
non-combustible material and transfer to containers. Use clean non-sparking
tools to collect absorbed material. Large spills: Dike far ahead of liquid spill
for later disposal. Water spray may reduce vapor; but may not prevent ignition
in closed spaces. /Ethanol; Ethanol, solution/
First aid: Move victim to
fresh air. Call emergency medical care. Apply artificial respiration if victim
is not breathing. Administer oxygen if breathing is difficult. Remove and
isolate contaminated clothing and shoes. In case of contact with substance,
immediately flush skin or eyes with running water for at least 20 minutes. Wash
skin with soap and water. Keep victim warm and quiet. Ensure that medical
personnel are aware of the material(s) involved, and take precautions to protect
themselves. /Ethanol; Ethanol, solution/
Odor Threshold:
10 PPM
1.00X10-1 mg/l gas (detection
in air, purity not specified)
1.00X10+2 mg/l liquid
(detection in water, purity not specified)
9.23 ppm (detection in water,
purity not specified)
2.50X10-1 ppm (detection in
water, purity not specified)
5.75 ppm (detection in water,
purity not specified)
1.88X10-1 ppm (detection in
water, purity not specified)
1.00X10+2 ppm (detection in
water, purity not specified)
1.00X10+1 ppm (recognition in
air, chemically pure)
4.40X10+3 ppm (detection in
air, purity not specified)
2.40X10+13 molecules/cu cm (in
air, purity not specified)
3.30X10+13 molecules/cu cm (in
air, purity not specified)
Odor thresholds: 0.3420 mg/cu
m (low) 9690.000 mg/cu m (high).
Fire Potential:
DANGEROUS WHEN EXPOSED TO HEAT
OR FLAME ... .
NFPA Hazard Classification:
Health: 0. 0= Materials that,
on exposure under fire conditions, offer no hazard beyond that of ordinary
combustible material.
Flammability: 3. 3= This
degree includes Class IB and IC flammable liquids and materials that can be
easily ignited under almost all normal temperature conditions. Water may be
ineffective in controlling or extinguishing fires in such materials.
Reactivity: 0. 0= This degree
includes materials that are normally stable, even under fire exposure
conditions, and that do not react with water. Normal fire fighting procedures
may be used.
Flammable Limits:
LOWER 3.3%; UPPER 19% (BY VOL)
Flash Point:
55 DEG F (13 DEG C) (CLOSED
CUP)
55 deg F (closed cup); 64 deg
F (open cup)
63 deg F (17 deg C) (closed
cup) /96%/
79 deg F (24 deg C) (closed
cup) /50%/
144 deg F (62 deg C) (closed
cup) /5%/
Autoignition Temperature:
685 DEG F (363 DEG C)
Fire Fighting Procedures:
The most appropriate
extinguishers are carbon dioxide and dust; Water may be used, provided it is
/used/ in large amounts.
Do not extinguish fire unless
flow can be stopped. Use water in flooding quantities as fog. Solid streams of
water may be ineffective. Cool all affected containers with flooding quantities
of water. Apply water from as far a distance as possible. Use
"alcohol" foam, dry chemical ... .
Explosive Limits & Potential:
VAPOR MAY EXPLODE IF IGNITED
IN AN ENCLOSED AREA.
Hazardous Reactivities & Incompatibilities:
STRONG OXIDIZING AGENTS SUCH
AS CHLORINE, PERMANGANATE, OR CHROMATE IN ACID SOLN REACT, IN SOME CASES
VIOLENTLY, WITH ALCOHOL TO PRODUCE OXIDATION PRODUCTS.
A solution of permanganic acid
(or its explosive anhydride dimanganese heptoxide) ... will explode on contact
with ... ethanol ... .
Solid /ruthenium (VIII) oxide/
or its concentrated solutions or vapor, tends to oxidize ethanol, cellulose
fibers ... explosively.
Bromine pentafluoride ...
contact with ... ethanol is likely to cause fire or explosion ... .
... Ethanol ignites then
explodes /upon contact with nitrosyl perchlorate/.
... Ethanol ... ignites on
contact with /chromyl/ chloride ... .
Uranium hexafluoride /reacts
violently/ with ethanol ... .
... Ethanol ... ignites in
contact with /iodine heptafluoride/ gas ... .
Attempted crystallization of
... /uranyl perchlorate/ from ethanol caused an explosion ... .
Interaction ... /between/
water, methanol or ethanol /and acetyl bromide/ is violent, hydrogen bromide
being evolved.
Reclaimed silver nitrate
crystals, damp with the alcohol used for washing, exploded violently when
touched with a spatula ... .
A 15% soln of nitric acid in
ethanol was used to etch a bismuth crystal. After removing the metal, the
mixture decomp vigorously.
Violent reaction on mixing /of
disulfuryl difluoride & ethanol/ at ambient temp.
The desiccant /magnesium
perchlorate/ in a drying tube, accidentally exposed to ethanol vapor, was left
for several months. The explosion which occurred when the desiccant was scraped
out was certainly due to formation of ethyl perchlorate.
Addition of platinum black
catalyst to ethanol caused ignition. Pre-reduction with hydrogen and/or nitrogen
purging of air prevented this.
Contact of 1.5 g portions of
the solid /potassium tert-butoxide/ ... with ... /ethanol vapor for 7 min/
caused ignition ... .
Silver oxide and ammonia or
hydrazine slowly form explosive silver nitride and, in presence of alcohol,
silver fulminate may also be produced.
Air must be excluded during
exothermic interaction of ethanol with sodium finely dispersed in hydrocarbons
to avoid the possibility of hydrogen air mixture explosions.
In the preparation of ethyl
polysilicate by mixing tetrachlorosilane and industrial methylated spirit
containing some water, failure of the agitator is thought to have led to
layering of the alcohol over the dense chloride. Evolution of hydrogen chloride
led to mixing of the layers, and a greatly incr rate of reaction and
self-accelerating gas evolution which burst the reactor.
Acetyl chloride reacts
violently with ethyl alcohol or water.
A mixture of silver oxide plus
ethyl alcohol and aq ammonia forms the very sensitive silver nitride.
A little calcium hypochlorite
added to ethyl alcohol or glycerol will result in a violent explosion after a
short time.
No really safe conditions
exist under which ethyl alcohol and chlorine oxides can be handled.
The addition of alcohols to
highly concn hydrogen peroxide forms powerful explosives which can be detonated
by shock.
The Petrov method of preparing
1-iodo-2-ethoxy-3-butene calls for addition of 15 g of mercuric oxide to 0.11
molar ethyl alcohol in 25 ml of methyl alcohol, followed by 25 g of powdered
iodine at -10 to -15 deg C, filtration, and dilution. A change in the procedure
used 1 molar ethyl alcohol. While the alcohol was being distilled off under
vacuum, a violent explosion occurred.
A violent explosion occurred
when manganese perchlorate, absolute alcohol and 2,2-dimethoxypropane were
gently refluxed for about two hr under a stream of nitrogen.
Alcohols should not be mixed
with mercuric nitrate, as explosive mercury fulminate may be formed.
Certain metal perchlorates
recrystallized from benzene or ethyl alcohol can explode spontaneously. /Metal
perchlorates/
In mineral analysis the
potassium cation is sometimes identified by adding perchloric acid in the
presence of ethyl alcohol concn. Explosions frequently occur that are due to the
spontaneous decomp of ethyl perchlorate formed during concn and of residual
perchloric acid.
To dispose of a
sodium-potassium waste, it was placed in a glove box, which was then purged with
argon for 10 min. When 10 ml of alcohol was added to the waste, an immediate
pressure rise caused the glove to burst and flame issued from the port. Also, a
highly oxidized sphere of potassium was cut in two and one half was dropped into
a dish of alcohol; an immediate explosion shattered the dish. Potassium
superoxide was considered the cause of both incidents.
Addition of air, or alcohol,
or moisture to sodium hydrazide can produce an explosion.
Strong oxidizers, potassium
dioxide, bromine pentafluoride, acetyl bromide, acetyl chloride, platinum,
sodium.
Immediately Dangerous to Life or Health:
3300 ppm [Based on 10% of the
lower explosive limit for safety considerations even though the relevant
toxicological data indicated that irreversible health effects or impairment of
escape existed only at higher concentrations.]
Protective Equipment & Clothing:
ALL-PURPOSE CANISTER; SAFETY
GOGGLES.
Personal protective equipment
... should be provided where there is ... prolonged skin contact.
Protective clothing should be
worn by persons who are exposed to ethanol and should be composed of natural
rubber, neoprene, nitrile, or vitron as these compounds have breakthrough times
(ie the time it takes for a compound to move from the outer surface of
protective clothing to the inner surface) of at least an hour or more.
Breakthrough times geater than
one hour reported by (normally, two or more testers for butyl rubber (butyl),
natural rubber (nat.rub) neoprene (neop), nitrile rubber (nitrile) and viton.
Breakthrough times less (usually significantly less) than one hour reported by
(normally) two or more testers for polyvinyl alcohol (PVA) and polyvinyl
chloride (PVC). No data for neoprene/styrene-butadiene rubber (neop/SBR),
nitrile rubber/polyvinyl chloride (nitrile/PVC), polyethylene (PE), polyurethane
(PU), and styrene-butadiene rubber (SBR).
Wear appropriate personal
protective clothing to prevent skin contact.
Wear appropriate eye
protection to prevent eye contact.
Recommendations for respirator
selection. Max concn for use: 3300 ppm. Respirator Class(es): Any supplied-air
respirator. Any self-contained breathing apparatus with a full facepiece.
Recommendations for respirator
selection. Condition: Emergency or planned entry into unknown concn or IDLH
conditions: Respirator Class(es): Any self-contained breathing apparatus that
has a full facepiece and is operated in a pressure-demand or other
positive-pressure mode. Any supplied-air respirator that has a full facepiece
and is operated in a pressure-demand or other positive-pressure mode in
combination with an auxiliary self-contained breathing apparatus operated in
pressure-demand or other positive-pressure mode.
Recommendations for respirator
selection. Condition: Escape from suddenly occurring respiratory hazards:
Respirator Class(es): Any appropriate escape-type, self-contained breathing
apparatus.
Preventive Measures:
Good ventilation will prevent
the formation of harmful concentrations of alcohol vapors ... Arrangements
should be made by the provision of sills and curbs and by the design of floors
to limit the spread of escaping liquid and to conduct it to a safe place ...
Precautions should be taken ... by the provision of flameproof electrical
installations and equipment, to prevent sources of ignition where large
quantities of ethyl alcohol are made or used /and/or stored/.
If material /is/ not on fire
and not involved in fire: Keep sparks, flames, and other sources of ignition
away. Keep material out of water sources and sewers. Build dikes to contain flow
as necessary. Attempt to stop leak if without undue personnel hazard. Use water
spray to disperse vapors and dilute standing pools of liquid.
Avoid breathing vapors. Keep
upwind. Do not handle broken packages unless wearing appropriate personal
protective equipment. Wash away any material which may have contacted the body
with copious amounts of water or soap and water.
Evacuation: If material
leaking (not on fire) consider evacuation from downwind area based on amount of
material spilled, location and weather conditions.
Employees who handle liquid
isobutyl alcohol should wash their hands before eating or smoking. /Isobutyl
alcohol/
The worker should immediately
wash the skin when it becomes contaminated.
Work clothing that becomes wet
should be immediately removed due to its flammability hazard.
Contact lenses should not be
worn when working with this chemical.
Shipment Methods and Regulations:
No person may /transport,/
offer or accept a hazardous material for transportation in commerce unless that
person is registered in conformance ... and the hazardous material is properly
classed, described, packaged, marked, labeled, and in condition for shipment as
required or authorized by ... /the hazardous materials regulations (49 CFR
171-177)./
The International Air
Transport Association (IATA) Dangerous Goods Regulations are published by the
IATA Dangerous Goods Board pursuant to IATA Resolutions 618 and 619 and
constitute a manual of industry carrier regulations to be followed by all IATA
Member airlines when transporting hazardous materials.
The International Maritime
Dangerous Goods Code lays down basic principles for transporting hazardous
chemicals. Detailed recommendations for individual substances and a number of
recommendations for good practice are included in the classes dealing with such
substances. A general index of technical names has also been compiled. This
index should always be consulted when attempting to locate the appropriate
procedures to be used when shipping any substance or article.
Storage Conditions:
Keep tightly closed, cool and
away from flame.
STORAGE TEMP: AMBIENT.
VENTING: OPEN (FLAME ARRESTER) OR PRESSURE VACUUM.
Protect containers against
physical damage. Underground storage tanks outside the building is preferred for
use of large quantities. Small amt may be stored outside the building in the
original shipping containers. ... Should not be stored with perchlorates,
peroxides, chromic acid and nitric acid.
Cleanup Methods:
Land spill: Apply appropriate
foam to diminish vapor and fire hazard.
Water spill: Use natural
barriers or oil spill control booms to limit spill travel. Allow to aerate.
Air spill: Apply water spray
or mist to knock down vapors.
Disposal Methods:
SRP: At the time of review,
criteria for land treatment or burial (sanitary landfill) disposal practices are
subject to significant revision. Prior to implementing land disposal of waste
residue (including waste sludge), consult with environmental regulatory agencies
for guidance on acceptable disposal practices.
The following wastewater
treatment technologies have been investigated for ethanol: Biological Treatment.
Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit:
Table Z-1 8-hr Time Weighted Avg: 1000 ppm (1900 mg/cu m).
Threshold Limit Values:
8 hr Time Weighted Avg (TWA):
1000 ppm.
Excursion Limit
Recommendation: Excursions in worker exposure levels may exceed three times the
TLV-TWA for no more than a total of 30 min during a work day, and under no
circumstances should they exceed five times the TLV-TWA, provided that the
TLV-TWA is not exceeded.
A4; Not classifiable as a
human carcinogen.
NIOSH Recommendations:
Recommended Exposure Limit: 10
Hr Time-Weighted Avg: 1000 ppm (1900 mg/cu m).
Immediately Dangerous to Life or Health:
3300 ppm [Based on 10% of the
lower explosive limit for safety considerations even though the relevant
toxicological data indicated that irreversible health effects or impairment of
escape existed only at higher concentrations.]
Other Occupational Permissible Levels:
MAXIMUM ACCEPTABLE CONCN (MAC)
USSR 1000 mg/cu m
Other recommendations: the
USSR (1967) East Germany (1973) and Czechoslovakia (1969) limits are 500 ppm;
West Germany (1974) and Sweden (1975) 1000 ppm.
Manufacturing/Use Information:
Major Uses:
IN ALCOHOLIC BEVERAGES;
MANUFACTURING OF DENATURED ALCOHOLS; PHARMACEUTICALS; IN PERFUMERY; IN ORGANIC
SYNTHESIS; OCTANE BOOSTER IN GASOLINE; SOLVENT AND DEHYDRATING AGENT.
IN SYNTHETIC RUBBER, PAINT
& LACQUER, & EXPLOSIVES INDUSTRIES; ANTI-FREEZE AGENT.
Manufacturing of surface
coatings; gasohol, yeast growth medium
Solvent for resins, fats,
fatty acids, oils, hydrocarbons
DIRECT FOOD ADDITIVES
Manufacturing of acetaldehyde,
acetic acid, ethylacetate, ethylchloride, ethylether, butadiene, ethylene
dibromide, plastics and plasticizers, soap and cleaning preparations, dyes,
explosives
MEDICATION (VET):
MEDICATION
In inks
For surgical suture packaging
Ethylene is manufactured by
the vapor phase dehydration of ethanol
The addition of one mole of
ethylene oxide to ethanol gives ethylene glycol monoethyl ether. Dilute soln of
alcohol as fermented worts are oxidized by air at 30-40 deg C in the presence of
various organisms to produce dilute acetic acid as vinegar.
Mono-, di-, and triethylamines,
produced by catalytic reaction of ethanol with ammonia, are a significant outlet
for ethanol. In the synthesis of ethyl acrylate, the esterification of acrylic
acid is a major use for ethanol.
The addition of ethanol to
acetylene gives ethyl vinyl ether.
Manufacturers:
American Development Corp, Hq,
3200 Park Center Dr, Costa Mesa, CA 92626, (714) 641-6660; Production site:
Hastings, NE 68901
Archer Daniels Midland Co, Hq,
PO Box 1470, Decatur, IL 62525, (217) 424-5200; ADM Processing Division;
Production sites: Cedar Rapids, IA 52413; Clinton, IN 47800; Decatur, IL 62500;
Peoria, IL 61600
CENEX, Hq, PO Box 43089, St
Paul, MN 55164, (612) 451-5151; CENEX Agrifuels Co, Road 9, Walhalla, ND 58282
Eastman Kodak Co, Hq, 343
State St, Rochester, NY 14650, (716) 724-4000, Eastman Chemical Products, Inc,
PO Box 431, Kingsport, TN 37662; Texas Eastman Co; Production site: Longview, TX
75607
Edington Oil Co, Hq, 2400 E
Artesia Boulevard, Long Beach, CA 90805, Subsidiary: Agrifuels Refining Corp,
New Iberia, LA 70560, (318) 367-3511
Energy Fuels Development Corp,
Hq, PO Box 892, Portales, NM 88130, (505) 356-8535
Georgia-Pacific Corp, Hq, 133
Peachtree St NE, Atlanta, GA 30303, (404) 521-4000; Chemical Division;
Production site: 300 Laurel St, Bellingham, WA 98225
Grain Processing Corp, Hq,
1600 Oregon St, Muscatine, IA 52761, (319) 264-4265
High Plains Corporation, Hq,
412 N First St, Colwich, KS 67030, (316) 796-1234
Kentucky Agricultural Energy
Corp, 3150 Nashville Rd, Franklin, KY 42134, (502) 586-9586
Midwest Grain Products, Inc,
Hq, 1300 Main St, (PO Box 130) Atchison, KS 66002, (913) 367-1480; Production
sites: Atchison, KS 66002; South Front St, Pekin, IL 61554
New Energy Co of Indiana, Hq,
3201 W Calvert St, South Bend, IN 46680, (219) 233-3116
Pekin Energy Co, Hq, PO Box
10, Pekin, IL 61555, (309) 347-9200
Quantum Chemical Corp, Hq, 99
Park Ave, New York, NY 10016, (212) 949-5000; USI Division, 11500 Northlake Dr,
Cincinnati, OH 45249; Production site: Tuscola, IL 61953
South Point Ethanol, County Rd
1, Old US 52, PO Box 1004, South Point, OH 45680, (614) 377-2765
Staley Continental, Inc, AE
Staley Manufacturing Co, Hq, 2200 East Eldorado St, Decatur, IL 62525, (217)
423-4411; Sweetener Business Group, Ethanol Division, Production site: Loudon,
TN 37774
Tennol Energy Co, Hq, 1901
Research Blvd, Suite 430, Rockville, MD 20850, (301) 738-1933; Production site:
Jasper, TN 37347
Union Carbide Corp, Hq, Old
Ridgebury Rd, Danbury, CT 06817, (203) 794-2000; Chemicals and Plastics Business
Group, Solvents and Coatings Materials Division; Production site: Texas City, TX
77591
Universal Foods Corp, Hq, 433
E Michigan St, Milwaukee, WI 53202, (414) 271-1820; Fermentation Division;
Production site: Juneau, WI 53201
Dow Chemical Co, 2020 Willard
Highway, Dow Center, Midland, MI 48686-0994, (517) 636-6125 /Ethyl alcohol,
synthetic/
Eastman Kodak Co, Hq, 34 State
St, Rochester, NY 14650, (716) 724-4000; Production site: Texas Eastman Co,
Division, Kingsport, TN 37662 /Ethyl alcohol, synthetic/
Hoechst Celanese Corp, Hq, Rt
202-206 N, Somerville, NJ 08876, (201) 231-2000/; Production sites: Chemical Grp
Division, 1250 W Mockingbird Lane, Dallas, TX 75247, Fibers Division, Charlotte,
NC 28232; Sou-Tex, Mount Holly, NC 28120 /Ethyl alcohol, synthetic/
Shell Oil Co, Hq, PO Box 3105,
Houston, TX 77002; Production site: Shell Chemical Co, Houston TX 77002 /Ethyl
alcohol, synthetic/
USI Chemical Co, Inc, USI
Division, 11500 Northlake Dr, Cincinnati, OH 45249, (513) 530-6580 /Ethyl
alcohol, synthetic/
Methods of Manufacturing:
... Chemical uses of n-butane
include manufacturing of acetic acid and by-product ... ethyl alcohol ... .
MANUFACTURED FROM ACETYLENE,
SULFITE WASTE LIQUORS, & SYNTHESIS GAS (CO + H); BY HYDROLYSIS OF ETHYL
SULFATE, & OXIDN OF METHANE.
a) From ethylene by direct
catalytic hydration ... b) fermentation of biomass, especially agricultural
wastes; c) enzymatic hydrolysis of cellulose
Ethanol can ... be obtained by
the reaction of methanol with synthesis gas at 185 deg C and under pressure
(6.9-20.7 MPa or 68-204 atm) in the presence of a cobalt octacarbonyl catalyst.
Using ... acid catalyst as in
the hydration of ethylene to ethanol, ethyl ether can be hydrated to the
alcohol. Catalysts that have been used for the hydration of ether include
phosphoric acid, sulfuric acid, hydrochloric acid, metallic oxides and
silicates. Sulfuric acid concn ranging from 5-25% at 200 deg C to 63-70% at
110-135 deg C and 1.01-1.42 MPa (10-14 atm) have been claimed.
General Manufacturing Information:
Industrial ethyl alcohol ...
always contains a denaturant, ie, a substance added to render it unfit or
undesirable as a beverage or vehicle for any medication intended for ingestion.
Denatured alcohols are designed to have objectionable odors or tastes and to
provoke vomiting or to induce significant systemic toxicity. The IRS and federal
regulations recognize two classes of denatured alcohol, completely denatured
(CD) and specifically denatured (SD).
... Wood consists of 2/3
carbohydrates, considerable attention has been given to the potential of wood
residues as a raw material for conversion to ethanol.
Formulations/Preparations:
Grades: USP (95% by vol);
Absolute; Pure; Completely denatured; Specially denatured; Industrial; Various
proofs ... .
Materials containing alcohol:
Apple Distillate K 2/032410; Arnica Distillate 2/378370; Birch Distillate
2/384280; Chamomille Distillate 2/380930; Linden Blossom Distillate 2/382920
To every 100 gal of ethyl
alcohol add: Four gal of methyl alcohol and one gal of methyl isobutyl ketone;
or four gal methyl alcohol and 1/8 avoirdupois oz denatonium benzoate, NF
To every 100 gal of ethyl
alcohol add: One-half gal benzene or one-half gal rubber hydrocarbon solvent.
To every 100 gal of ethyl
alcohol add: Thirty-three pounds, or more metallic sodium and either one-half
gal benzene or one-half gal rubber hydrocarbon solvent
To every 100 gal of ethyl
alcohol add: Five gal methyl alcohol
To every 100 gal of ethyl
alcohol add: One gal of pine tar NF
To every 100 gal of ethyl
alcohol add: One gal of the following solution: Five gal of an aq soln
containing 40% nicotine; and 3.6 avoirdupois oz of methylene blue, NF; water
sufficient to make 100 gal
To every 100 gal of ethyl
alcohol add: Five gal of benzene
To every 100 gal of ethyl
alcohol add: Ten gal of ethyl ether
To every 100 gal of ethyl
alcohol add: Five-hundredths gal of bone oil (Dipple's oil)
To every 100 gal of ethyl
alcohol add: One hundred gal of ethyl ether
To every 100 gal of ethyl
alcohol add: Ten gal of formaldehyde soln (USP)
To every 100 gal of ethyl
alcohol add: Ten gal of acetone, NF
To every 100 gal of ethyl
alcohol add: Three pounds of salicyclic acid, USP, one pound resorcin, USP, and
1 gal bergamont oil, NF, or bay oil, NF
To every 100 gal of ethyl
alcohol add: Eight gal of acetone, NF and 1.5 gal of methyl isobutyl ketone
To every 100 gal of ethyl
alcohol add: Twenty pounds of iodine, USP and 15 pounds of either potassium or
sodium iodide USP
To every 100 gal of ethyl
alcohol add: A soln composed of 20 pounds of iodine USP, 15 pounds of potassium
or sodium iodide USP and 15 pounds of water.
To every 100 gal of ethyl
alcohol add: One gal of rosemary oil, NF and 30 lb of camphor, USP
To every 100 gal of ethyl
alcohol add: Thirty-five lb of camphor, USP and 1 gal of clove oil, USP
To every 100 gal of ethyl
alcohol add: One gal of lavender oil, USP and 100 lb of medicinal soft soap, USP
To every 100 gal of ethyl
alcohol add: Ten gal of methyl alcohol
To every 100 gal of ethyl
alcohol add: One hundred lb of glycerol, USP and 20 lb of hard soap, NF
To every 100 gal of ethyl
alcohol add: Thirty lb of methyl violet, USP
To every 100 gal of ethyl
alcohol add: 29.75 gal of ethyl acetate having an ester content of 100% by wt or
the equivalent thereof not to exceed 35 gal of ethyl acetate with an ester
content of not less than 85% by wt
To every 100 gal of ethyl
alcohol add: 4.25 gal of ethyl acetate having an ester content of 100% by wt or
the equivalent thereof not to exceed 5 gal of ethyl acetate with an ester
content of not less than 85% by wt
To every 100 gal of ethyl
alcohol add: 3 gal of ammonia, aq, 27 to 30% by wt: three gal of strong ammonia
soln, USP: 17.5 lb of caustic soda, liq grade, containing 50% sodium hydroxide
by wt: or 12.0 lb of caustic soda, liq grade, containing 73% sodium hydroxide by
wt.
To every 100 gal of ethyl
alcohol add: 45 fluid oz of eucalyptol, USP, 30 avoirdupois oz of thymol, NF and
20 avoirdupois oz of mentol, USP
To every 100 gal of ethyl
alcohol add: Ten lb of any one or a total of 10 lb of two or more of the oils
and substances listed below: anethole, USP; anise oil, USP; bay oil (myrcia
oil), NF; benzaldehyde, NF; bergamot oil, NF; bitter almond oil, NF; camphor,
USP; cedar leaf oil, USP, XIII; chlorothymol, NF; cinnamic aldehyde, NF, IX;
cinnamon oil (cassia oil), USP; citronella oil, natural; clove oil, USP; coal
tar, USP; eucalyptol, USP; eucalyptus oil, NF; eugenol, USP; guaiacol, NF;
lavender oil, USP; menthol, USP; mustard oil, volatile (allyl isothiocyanate),
USP, XII; peppermint oil, USP; phenol, USP; phenyl salicylate (salol), NF; pine
oil, NF; pine needle oil, dwarf, NF; rosemary oil, NF; safrol; sassafras oil,
NF; spearmint oil, NF; spearmint oil, terpeneless; spike lavender oil, natural;
storax, USP; thyme oil, NF; thymol, NF; tolu balsam, USP; turpentine oil, NF;
wintergreen oil (methyl salicylate), USP
To every 100 gal of ethyl
alcohol add: 10 lb of menthol, USP and 1.25 gal of formaldehyde soln, USP
To every 100 gal of ethyl
alcohol add: Two and one-half lb of menthol, USP and 2.5 gal of formaldehyde
soln, USP
To every 100 gal of ethyl
alcohol add: (1) Six lb of boric acid, USP, 1 and 1/3 lb thymol, NF, 1 and 1/3
lb chlorothymol, NF and 1 and 1/3 lb menthol, USP; or (2) Seven lb of boric
acid, USP, and a total of 3 lb of any two or more denaturing materials listed
under SDA No 38-B
To every 100 gal of ethyl
alcohol add: Nine lb of sodium salicylate or salicylic acid, USP, 1.25 gal fluid
extract of quassia, NF, VII and 1/8 gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: Sixty avoirdupois oz of any one of the following alkaloids or salts
together with 1/8 gal of tertiary butyl alcohol: quinine, NF; quinine bisulfate,
NF; quinine hydrochloride, USP; cinchonidine; cinchonidine sulfate, NF, IX
To every 100 gal of ethyl
alcohol add: Two and 1/2 gal of diethylphthalate and 1/8 gal of tertiary butyl
alcohol
To every 100 gal of ethyl
alcohol add: One gal of diethylphthalate
To every 100 gal of ethyl
alcohol add: One gal of bay oil, NF and either 50 avoirdupois oz of quinine
sulfate, USP, 50 avoirdupois oz of quinine bisulfate, NF, or 200 avoirdupois oz
of sodium salicylate, USP
To every 100 gal of ethyl
alcohol add: One and one-half avoirdupois oz of brucine (alkaloid), or brucine
sulfate (NF, IX), or quassin, or one and one-half av oz of any combination of
two or of three of those denaturants, and 1/8 gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: One lb of sucrose octa-acetate and 1/8 gal of tertiary butyl
alcohol
To every 100 gal of ethyl
alcohol add: One-sixteenth avoirdupois oz of denatonium benzoate, NF, (Bitrex)
and 1/8 gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: Three gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: Eighty g of potassium iodide, USP and 109 g of red mercuric iodide,
NF or 95 g of thimerosal, NF or 76 g of any of the following: phenyl mercuric
nitrate, NF; phenyl mercuric chloride, NF; or phenyl mercuric benzoate
To every 100 gal of ethyl
alcohol add: Ten gal of n-butyl alcohol
To every 100 gal of ethyl
alcohol add: Three hundred lb of refined white or orange shellac
To every 100 gal of ethyl
alcohol add: 25 fluid oz of phenol, USP and 4 fluid oz of wintergreen oil
(methyl salicylate), USP
Grades of purity: Anhydrous
(200 proof); 190 proof
Preparations: Alcohol &
Dextrose Injectio, USP; Ethanol for Disinfection; Evaporating Lotion; High
alcoholic Elixir; Iso-alcoholic Elixir; Low alcoholic Elixir; Spirit Ear-drops
Consumption Patterns:
MOTOR FUEL SUPPLEMENT, 25%;
SOLVENT FOR: TOILETRIES & COSMETICS, 11%; COATINGS, INKS & PROPRIETARY
BLENDS, 11%; DETERGENTS, DISINFECTANTS & FLAVORINGS, 7%; PROCESSING, 5%;
PHARMACEUTICALS, 2%; OTHER SOLVENT USES, 2%; CHEM INTERMED FOR: GLYCOL ETHERS,
6%; ETHYL ACRYLATE, 6%; ETHYL AMINES, 5%; ETHYL ACETATE, 3%; ACETALDEHYDE, 3%;
OTHER USES, 4% (1981 NON-BEVERAGE USE)
Chemicals manufacture, 40%;
vinegar, 8%; solvents: coatings & inks, 15%; solvents: cosmetics &
toiletries, 15%; solvents: foods flavors, and pharmaceuticals, 12%; other
solvents, 5%; miscellaneous, 5% (1984 estimate)
CHEMICAL PROFILE: Synthetic
ethanol: chemical intermediate (for ethyl acetate, ethyl acrylate, glycol
ethers, ethylamines and other), 30%; toiletries and cosmetics, 20%; coatings
solvent, 15%; vinegar, 10%; household cleaners, 7%; detergents, 5%;
pharmaceuticals, 5%; printing inks, 3%; miscellaneous, 5%. Fermentation ethanol:
fuel component, 90%; beverages, 8%; industrial (chemical and solvent) uses, 2%
(1988).
CHEMICAL PROFILE: Ethanol.
Demand: Synthetic/1987: 210 million gallons; 1988: 215 million gallons; 1992
/projected/: 230 million gallons. (Includes 15 to 20 million gallons of
synthetic ethanol imports; exports are negligible). Fermentation/1987: 860
million gallons; 1988: 950 million gallons; 1992 /projected/: 1,150 million
gallons (Foreign trade is minimal) (1988).
U. S. Production:
(1977) 8.42X10+11 G (NOT INCL
BEVERAGE)
(1982) 9.33X10+11 G (NOT INCL
BEVERAGE)
(1984) 5.43X10+8 gal
/estimate/
(1985) 6.49X10+8 lb /Synthetic
only for non-beverage purposes/
(1986) 5.11X10+8 lb /Synthetic
only/
(1987) 5.74X10+8 lb
U. S. Imports:
(1977) 5.9X10+10 G (NOT INCL
BEVERAGE)
(1982) 1.09X10+11 G (NOT INCL
BEVERAGE)
(1985) 1.62X10+11 gal (for
nonbeverage purposes)
(1986) 1.57X10+8 gal
U. S. Exports:
(1978) 2.18X10+10 G (NOT INCL
BEVERAGE)
(1983) 7.53X10+9 G (NOT INCL
BEVERAGE)
(1985) 3.24X10+6 gal
(1987) 1.04X10+6 gal
(1988) 4.59X10+5 gal
Laboratory Methods:
Clinical Laboratory Methods:
RAPID VAPOR PHASE METHOD FOR
DETERMINING ETHANOL IN BLOOD & URINE BY GAS CHROMATOGRAPHY, AM J CLIN PATHOL,
46, 152, 1966.
BLOOD OR URINE,
SPECTROPHOTOMETRY AT 450 OR 350 NM; DUBOWSKI, K, TESTS FOR ALCOHOL ... COMMITTEE
ON MEDICOLEGAL PROBLEMS, ED, US MEDICAL ASSOCIATION, CHICAGO, ILL, 1968, 61.
AUTOMATED BLOOD ALCOHOL
DETERMINATION (ADH-METHOD) USING THE LKB-SUBSTRATE ANALYZER 2074 WAS DISCUSSED.
DEPROTEINATED SERUM OR BLOOD SAMPLES WERE INCUBATED WITH NAD & ALCOHOL
DEHYDROGENASE FOR 15 MIN AT 25 DEG C, EXTINCTION DETERMINED @ 340 NM. ACCURACY
96.76%, STANDARD DEVIATION 0.049.
NIOSH 8002: Analytes: methyl
ethyl ketone, ethanol, toluene (simultaneous); Specimen: venous blood;
Technique: gas chromatography, flame ionization detector; Carrier gas: helium,
25 ml/min; Column: glass, 3m X 2mm ID, 5% Carbowax 20 m on 100/120 mesh
Chromosorb WHP; Range: 0.01 to 0.6 mg/ml; Precision (relative standard
deviation): 0.056 (0.1 mg/ml blood) /2-Butanone, ethanol, & toluene in
blood/
A novel mouth cup device for
sampling breath from unconscious subjects and analysis with a hand held breath
alcohol instrument, the Alcolmeter SD-2 are described. The Alcolmeter SD-2
operates by means of an electrochemical detector and is calibrated to read
directly in terms of blood alcohol content on the basis of a 2300:1 blood/breath
ratio of ethanol. The mouth cup device was made from a disposable polypropylene
cup. The nasal tube is a polypropylene tube, 1.5 cm x 0.3 cm. The equipment was
evaluated in six healthy volunteers (three men and three women) 30 to 120 min
after they drank a moderate dose of alcohol. Three kinds of breath were
analyzed: end expired air from a conventional mouth tube; breath sampled from
the mouth cup; and air from a nasal tube supplied with the breath analyzer. The
ethanol concentration in breath from the mouth cup was slightly less than in end
expired air but significantly greater than in nasal air. Results with mouth tube
and mouth cup correlated highly with blood ethanol concentration as determined
by gas chromatography; nasal tube air correlated less well.
Analytic Laboratory Methods:
Alcohol by vol in distilled
liquors was determined by a Pycnometer method. Samples containing 60% or less
alcohol by vol as well as samples containing more than 60% by vol were
determined.
Alcohol by vol in distilled
liquors was determined by a hydrometer method. Applicable to spirits containing
< or = 600 mg extract/100 ml.
Alcohol in distilled liquors
by a densitometric method. Mettler/Paar DMA 55D, with adapter No 5771 which
permits continuous flow of sample through U-tube was used.
Alcohol in distilled liquors
by Williams Field Test.
Alcohol by vol in liqueur-type
and alcoholic dairy products by densitometer method. Applicable to products
containing dissolved solids.
Alcohol by vol in beer by a
specific gravity method.
Ethanol in beer a by gas
chromatographic method. ... n-propanol internal standar is added to sample, and
ethanol is determined by gas chromatography using flame ionization detection.
Alcohol in wines by vol from
refraction (rapid method). Determine immersion refractometer reading of
distillate ... and find corresponding % alcohol ... .
Alcohol in wines by dichromate
oxidation. Sample is steam-distilled into acidified potassium dichromate soln.
Oxidation of ethanol to ethyl acetate is completed by heating. Unreacted
dichromate is determined by titration with standard ferric ammonium sulfate soln,
using o-phenanthroline as indicator. Calculate % alcohol by vol ... .
Alcohol in wines by a gas
chromatographic method.
Alcohol in vanilla extract by
a pycnometer method.
Alcohol in flavors /lemon,
orange, lime, almond, cassia, cinnamon, and clove extracts/ by a gas
chromatographic method.
... Ethyl alcohol in cosmetics
by a gas chromatographic method.
... Alcohol in drugs by gas
chromatographic method. Applicable to liquid preparations containing ethanol
with isopropanol or acetone or individual cmpd.
TRACE ODOR POLLUTANTS IN MODEL
GARBAGE & WASTE DISPOSAL PLANT WERE IDENTIFIED BY GC & MASS
SPECTROSCOPY. NEUTRAL AND AMINE CMPD WERE COLLECTED BY THE COLD TRAP METHOD IN
THE SAMPLING HEAD SPACE GAS OF THE MODEL GARBAGE. ETHYL ALC WAS IDENTIFIED AS
ONE OF THE NEUTRAL COMPONENTS.
A modified variant of the
purge-and-trap gas chromatographic analysis of volatile organic carbon compounds
in water was designed. Samples are purged in an ultrapure helium gas stream
using an open loop arrangement. Volatile eluates are trapped onto selective
adsorbents packed inside stainless steel tubes connected in series. After
stripping, the adsorbent tubes are disconnected, fitted with analytical
desorption caps and sequentially desorbed on a thermal desorber. The desorbed
organics are trapped on a packed cold trap prior to flash volatilization of the
volatiles across a fused silica transfer line onto a capillary column.Ethanol
was among the 200 organic compounds separated using flame ionization and ion
trap detection. The method is capable of quantitation down to 5 ng/l per
component. The recoveries of ethanol from water at 30 and 60 C were 59 and 87%,
respectively.
Sampling Procedures:
NIOSH 1400: Analyte: ethanol;
Matrix: air; Sampler: solid sorbent tube (coconut shell charcoal, 100 mg/50 mg);
Flow rate: 0.05 l/min; Vol: min: 0.1 l, max: 1 l; Stability: store in freezer;
analyze as soon as possible /Alcohols I, ethanol/
NIOSH 8002: Analytes: methyl
ethyl ketone, ethanol, toluene (simultaneous); Specimen: venous blood, after 2
or more hr of exposure; Container: 5 ml heparin coated vacuum tube; Shipment:
air express at 4 deg C; Sample stability: stable at 4 deg C for 3 wk; Controls:
Pre-shift whole blood samples as well as whole blood samples from non exposed
controls /2-Butanone, ethanol, & toluene in blood/
A novel mouth cup device for
sampling breath from unconscious subjects and analysis with a hand held breath
alcohol instrument, the Alcolmeter SD-2 are described. The mouth cup device was
made from a disposable polypropylene cup. The nasal tube is a polypropylene
tube, 1.5 cm x 0.3 cm.
Special References:
Special Reports:
Sato C et al; Alcohol Relat
Dis Gastroenterol: p.172-84 (1985). A review with many references on the
interactions of ethanol with drugs and xenobiotics. The effects of ethanol on
absorption, plasma protein binding, hepatic blood flow, distribution, hepatic
uptake, and phase I & II hepatic metabolism are briefly summarized and the
clinical relevance of the observed changes is discussed.
Lieber CS, Leo MA; Falk Symp
39 Hepatology: 15-36 (1985). A review with 60 references on the direct effects
of ethanol on vitamin A metabolism and resulting alterations of hepatic vitamin
A levels even at early stages of alcohol liver injury. Implication with regard
to vitamin A therapy in alcoholics and possible vitamin A toxicity were also
discussed.
Synonyms and Identifiers:
Synonyms:
ABSOLUTE ETHANOL
**PEER REVIEWED**
AETHANOL (GERMAN)
**PEER REVIEWED**
AETHYLALKOHOL (GERMAN)
**PEER REVIEWED**
ALCOHOL
**PEER REVIEWED**
ALCOHOL ANHYDROUS
**PEER REVIEWED**
ALCOHOL DEHYDRATED
**PEER REVIEWED**
ALCOHOL, ETHYL
**PEER REVIEWED**
ALCOOL ETHYLIQUE (FRENCH)
**PEER REVIEWED**
ALCOOL ETILICO (ITALIAN)
**PEER REVIEWED**
ALGRAIN
**PEER REVIEWED**
ALKOHOL (GERMAN)
**PEER REVIEWED**
ANHYDROL
**PEER REVIEWED**
COLOGNE SPIRIT
**PEER REVIEWED**
ETANOLO (ITALIAN)
**PEER REVIEWED**
ETHANOL 200 PROOF
**PEER REVIEWED**
Ethanol solution
**PEER REVIEWED**
ETHYL ALCOHOL
**PEER REVIEWED**
ETHYL ALCOHOL ANHYDROUS
**PEER REVIEWED**
ETHYLALCOHOL (DUTCH)
**PEER REVIEWED**
ETHYL HYDRATE
**PEER REVIEWED**
ETHYL HYDROXIDE
**PEER REVIEWED**
ETYLOWY ALKOHOL (POLISH)
**PEER REVIEWED**
FEMA NUMBER 2419
**PEER REVIEWED**
FERMENTATION ALCOHOL
**PEER REVIEWED**
GRAIN ALCOHOL
**PEER REVIEWED**
JAYSOL S
**PEER REVIEWED**
METHYLCARBINOL
**PEER REVIEWED**
MOLASSES ALCOHOL
**PEER REVIEWED**
NCI-C03134
**PEER REVIEWED**
POTATO ALCOHOL
**PEER REVIEWED**
SPIRITS OF WINE
**PEER REVIEWED**
TECSOL
**PEER REVIEWED**
TECSOL C
**PEER REVIEWED**
Formulations/Preparations:
Grades: USP (95% by vol);
Absolute; Pure; Completely denatured; Specially denatured; Industrial; Various
proofs ... .
Materials containing alcohol:
Apple Distillate K 2/032410; Arnica Distillate 2/378370; Birch Distillate
2/384280; Chamomille Distillate 2/380930; Linden Blossom Distillate 2/382920
To every 100 gal of ethyl
alcohol add: Four gal of methyl alcohol and one gal of methyl isobutyl ketone;
or four gal methyl alcohol and 1/8 avoirdupois oz denatonium benzoate, NF
To every 100 gal of ethyl
alcohol add: One-half gal benzene or one-half gal rubber hydrocarbon solvent.
To every 100 gal of ethyl
alcohol add: Thirty-three pounds, or more metallic sodium and either one-half
gal benzene or one-half gal rubber hydrocarbon solvent
To every 100 gal of ethyl
alcohol add: Five gal methyl alcohol
To every 100 gal of ethyl
alcohol add: One gal of pine tar NF
To every 100 gal of ethyl
alcohol add: One gal of the following solution: Five gal of an aq soln
containing 40% nicotine; and 3.6 avoirdupois oz of methylene blue, NF; water
sufficient to make 100 gal
To every 100 gal of ethyl
alcohol add: Five gal of benzene
To every 100 gal of ethyl
alcohol add: Ten gal of ethyl ether
To every 100 gal of ethyl
alcohol add: Five-hundredths gal of bone oil (Dipple's oil)
To every 100 gal of ethyl
alcohol add: One hundred gal of ethyl ether
To every 100 gal of ethyl
alcohol add: Ten gal of formaldehyde soln (USP)
To every 100 gal of ethyl
alcohol add: Ten gal of acetone, NF
To every 100 gal of ethyl
alcohol add: Three pounds of salicyclic acid, USP, one pound resorcin, USP, and
1 gal bergamont oil, NF, or bay oil, NF
To every 100 gal of ethyl
alcohol add: Eight gal of acetone, NF and 1.5 gal of methyl isobutyl ketone
To every 100 gal of ethyl
alcohol add: Twenty pounds of iodine, USP and 15 pounds of either potassium or
sodium iodide USP
To every 100 gal of ethyl
alcohol add: A soln composed of 20 pounds of iodine USP, 15 pounds of potassium
or sodium iodide USP and 15 pounds of water.
To every 100 gal of ethyl
alcohol add: One gal of rosemary oil, NF and 30 lb of camphor, USP
To every 100 gal of ethyl
alcohol add: Thirty-five lb of camphor, USP and 1 gal of clove oil, USP
To every 100 gal of ethyl
alcohol add: One gal of lavender oil, USP and 100 lb of medicinal soft soap, USP
To every 100 gal of ethyl
alcohol add: Ten gal of methyl alcohol
To every 100 gal of ethyl
alcohol add: One hundred lb of glycerol, USP and 20 lb of hard soap, NF
To every 100 gal of ethyl
alcohol add: Thirty lb of methyl violet, USP
To every 100 gal of ethyl
alcohol add: 29.75 gal of ethyl acetate having an ester content of 100% by wt or
the equivalent thereof not to exceed 35 gal of ethyl acetate with an ester
content of not less than 85% by wt
To every 100 gal of ethyl
alcohol add: 4.25 gal of ethyl acetate having an ester content of 100% by wt or
the equivalent thereof not to exceed 5 gal of ethyl acetate with an ester
content of not less than 85% by wt
To every 100 gal of ethyl
alcohol add: 3 gal of ammonia, aq, 27 to 30% by wt: three gal of strong ammonia
soln, USP: 17.5 lb of caustic soda, liq grade, containing 50% sodium hydroxide
by wt: or 12.0 lb of caustic soda, liq grade, containing 73% sodium hydroxide by
wt.
To every 100 gal of ethyl
alcohol add: 45 fluid oz of eucalyptol, USP, 30 avoirdupois oz of thymol, NF and
20 avoirdupois oz of mentol, USP
To every 100 gal of ethyl
alcohol add: Ten lb of any one or a total of 10 lb of two or more of the oils
and substances listed below: anethole, USP; anise oil, USP; bay oil (myrcia
oil), NF; benzaldehyde, NF; bergamot oil, NF; bitter almond oil, NF; camphor,
USP; cedar leaf oil, USP, XIII; chlorothymol, NF; cinnamic aldehyde, NF, IX;
cinnamon oil (cassia oil), USP; citronella oil, natural; clove oil, USP; coal
tar, USP; eucalyptol, USP; eucalyptus oil, NF; eugenol, USP; guaiacol, NF;
lavender oil, USP; menthol, USP; mustard oil, volatile (allyl isothiocyanate),
USP, XII; peppermint oil, USP; phenol, USP; phenyl salicylate (salol), NF; pine
oil, NF; pine needle oil, dwarf, NF; rosemary oil, NF; safrol; sassafras oil,
NF; spearmint oil, NF; spearmint oil, terpeneless; spike lavender oil, natural;
storax, USP; thyme oil, NF; thymol, NF; tolu balsam, USP; turpentine oil, NF;
wintergreen oil (methyl salicylate), USP
To every 100 gal of ethyl
alcohol add: 10 lb of menthol, USP and 1.25 gal of formaldehyde soln, USP
To every 100 gal of ethyl
alcohol add: Two and one-half lb of menthol, USP and 2.5 gal of formaldehyde
soln, USP
To every 100 gal of ethyl
alcohol add: (1) Six lb of boric acid, USP, 1 and 1/3 lb thymol, NF, 1 and 1/3
lb chlorothymol, NF and 1 and 1/3 lb menthol, USP; or (2) Seven lb of boric
acid, USP, and a total of 3 lb of any two or more denaturing materials listed
under SDA No 38-B
To every 100 gal of ethyl
alcohol add: Nine lb of sodium salicylate or salicylic acid, USP, 1.25 gal fluid
extract of quassia, NF, VII and 1/8 gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: Sixty avoirdupois oz of any one of the following alkaloids or salts
together with 1/8 gal of tertiary butyl alcohol: quinine, NF; quinine bisulfate,
NF; quinine hydrochloride, USP; cinchonidine; cinchonidine sulfate, NF, IX
To every 100 gal of ethyl
alcohol add: Two and 1/2 gal of diethylphthalate and 1/8 gal of tertiary butyl
alcohol
To every 100 gal of ethyl
alcohol add: One gal of diethylphthalate
To every 100 gal of ethyl
alcohol add: One gal of bay oil, NF and either 50 avoirdupois oz of quinine
sulfate, USP, 50 avoirdupois oz of quinine bisulfate, NF, or 200 avoirdupois oz
of sodium salicylate, USP
To every 100 gal of ethyl
alcohol add: One and one-half avoirdupois oz of brucine (alkaloid), or brucine
sulfate (NF, IX), or quassin, or one and one-half av oz of any combination of
two or of three of those denaturants, and 1/8 gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: One lb of sucrose octa-acetate and 1/8 gal of tertiary butyl
alcohol
To every 100 gal of ethyl
alcohol add: One-sixteenth avoirdupois oz of denatonium benzoate, NF, (Bitrex)
and 1/8 gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: Three gal of tertiary butyl alcohol
To every 100 gal of ethyl
alcohol add: Eighty g of potassium iodide, USP and 109 g of red mercuric iodide,
NF or 95 g of thimerosal, NF or 76 g of any of the following: phenyl mercuric
nitrate, NF; phenyl mercuric chloride, NF; or phenyl mercuric benzoate
To every 100 gal of ethyl
alcohol add: Ten gal of n-butyl alcohol
To every 100 gal of ethyl
alcohol add: Three hundred lb of refined white or orange shellac
To every 100 gal of ethyl
alcohol add: 25 fluid oz of phenol, USP and 4 fluid oz of wintergreen oil
(methyl salicylate), USP
Grades of purity: Anhydrous
(200 proof); 190 proof
Preparations: Alcohol &
Dextrose Injectio, USP; Ethanol for Disinfection; Evaporating Lotion; High
alcoholic Elixir; Iso-alcoholic Elixir; Low alcoholic Elixir; Spirit Ear-drops
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1170; Ethyl alcohol
IMO 3.2; Ethyl alcohol
(Ethanol or ethanol solutions including alcoholic beverages)
IMO 3.3; Ethyl alcohol
(Ethanol or ethanol solutions including alcoholic beverages)
Standard Transportation Number:
49 091 10; Ethyl Alcohol,
anhydrous, denatured in part with gasoline content not to exceed 5% (alcohol,
nos)
49 091 59; Cologne Spirits
(Ethanol or Ethyl Alcohol)
RTECS Number:
NIOSH/KQ6300000
Administrative Information:
Hazardous Substances Databank
Number: 82
Last Revision Date: 20020722
Last Review Date: Reviewed by SRP on 03/16/1990