1,2-DICHLOROETHANE
http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~0IVGrs:1
1,2-DICHLOROETHANE
Synonym: Ethylene Dichloride
CASRN: 107-06-2
Human Health Effects:
Toxicity Summary:
... The predominant source of exposure to 1,2-dichloroethane
by the general population is indoor and outdoor air, only minor amounts
being contributed by drinking water. Intake of 1,2-dichloroethane
from food is probably negligible. ... 1,2-dichloroethane
is readily absorbed following inhalation, ingestion or dermal exposure
and is rapidly and widely distributed throughout the body. It is rapidly and
extensively metabolized in rats and mice, with principally sulfur-containing
metabolites being eliminated in the urine in a dose-dependent manner. ... 1,2-Dichloroethane
appears to be metabolized via two principal pathways: the first involves
a saturable microsomal oxidation mediated by cytochrome P-450 to
2-chloroacetaldehyde and 2-chloroethanol followed by conjugation with
glutathione. The second pathway entails direct conjugation with glutathione to
form S-(2-chloroethyl)-glutathione, which may be nonenzymatically converted to a
glutathione episulfonium ion: this ion can form adducts with DNA. Although DNA
damage has been induced by the P-450 pathway in vitro, several lines of evidence
indicate that the glutathione conjugation pathway is probably of greater
significance than the P-450 pathway as the major route for DNA damage. ... The
acute toxicity of 1,2-dichloroethane is low in
experimental animals. ... The results of short-term and subchronic studies in
several species of experimental animals indicate that the liver and kidneys are
the target organs ... Morphological changes in the liver were observed in
several species following subchronic exposure to airborne concentrations ...
Increases in the relative liver weight have been observed in rats following
subchronic oral administration ... The carcinogenicity of 1,2-dichloroethane
has been investigated in a few limited bioassays on experimental animals
... Significant increases were not reported in the incidence of any type of
tumor in Sprague-Dawley rats or Swiss mice /by inhalation/ ... There was a
non-significant increase in the incidence of mammary gland adenomas and
fibroadenomas in female Sprague-Dawley rats exposed /by inhalation/ ... In
contrast, there was convincing evidence of increases in tumor incidence in two
species following ingestion. Significant increases in the incidence of tumors at
several sites (including squamous cell carcinomas of the stomach (males),
hemangiosarcomas (males and females), fibromas of the subcutaneous tissue
(males), adenocarcinomas and fibroadenomas of the mammary gland (females)) were
observed in Osborne-Mendel rats administered daily doses ... by gavage ...
Similar increases in the incidences of tumors at multiple sites (including
alveolar/bronchiolar adenomas (males and females), mammary gland adenocarcinomas
(females) and endometrial stromal polyp or endometrial stromal sarcoma combined
(females) and hepatocellular carcinomas (males)) occurred in B6C3F1 mice
administered daily doses ... by gavage ... The incidence of lung tumors (benign
papillomas) was significantly increased in female mice following repeated dermal
application of 1,2-dichloroethane ... Concomitant
exposure to inhaled 1,2-dichloroethane and disulfiram
in the diet resulted in an increased incidence of intrahepatic bile duct
cholangiomas and cysts, subcutaneous fibromas, hepatic neoplastic nodules,
interstitital cell tumors in the testes and mammary adenocarcinomas in rats,
compared to rats administered either compound alone or untreated controls. No
potential to initiate or promote tumor development was evident ... In in vitro
assays, 1,2-dichloroethane has been consistently
positive in mutagenicity bioassays in Salmonella typhimurium. In cultured
mammalian cells, 1,2-dichloroethane forms adducts with
DNA. It also induces unscheduled DNA synthesis in primary cultures of rodent and
human cells and gene mutation in several cell lines. Mutation frequency in human
cell lines has been correlated with differences in glutathione-S-transferase
activity. ... There is no evidence that 1,2-dichloroethane is
teratogenic in experimental animals. ... Acute incidental exposure to 1,2-dichloroethane
by inhalation or ingestion has resulted in a variety of effects in
humans, including effects on the central nervous system, liver, kidney, lung and
cardiovascular system. The potential carcinogenicity of 1,2-dichloroethane
in exposed human populations has not been extensively investigated. ...
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence in humans for the
carcinogenicity of 1,2-dichloroethane. There is
sufficient evidence in experimental animals for the carcinogenicity of 1,2-dichloroethane.
Overall evaluation: 1,2-Dichloroethane is
possibly carcinogenic to humans (Group 2B).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR
CLASSIFICATION: Based on the induction of several tumor types in rats and mice
treatd by gavage and lung papillomas in mice after topical application. HUMAN
CARCINOGENICITY DATA: None.
A4. Not classifiable as a human carcinogen.
Human Toxicity Excerpts:
/Ethylene dichloride/ ... is a
central nervous system depressant that produces symptoms ranging from nausea,
vomiting, headache, lightheadedness, & weakness to stupor, dysequilibrium,
coma, & respiratory arrest. Typically, in severe cases, CNS signs appear
first within several hr of exposure & are followed by a quiescent period. On
the second day, oliguria & hepatic transaminasemia may develop.
Subsequently, over the next several days, hepatorenal failure can occur. Severe
ingestions produce widespread organ damage (especially kidney, liver, &
adrenal gland) as well as gastrointestinal bleeding. Hepatic & renal
dysfunction has been complicated by fatal massive midzonal hepatic necrosis,
acute tubular necrosis, hypoglycemia, hypercalcemia, hypoprothombinemia, reduced
clotting factors, adrenal necrosis, & gastrointestinal hemorrhage. Heavy
exposure produces a bluish purple discoloration of the skin, dermatitis, &
corneal abrasions.
ACCIDENTAL ORAL INGESTION OF A SINGLE DOSE OF 0.5-1.0 G/KG HAS
BEEN REPORTED TO RESULT IN DEATH; AUTOPSY REVEALED LIVER NECROSIS AND FOCAL
ADRENAL DEGENERATION AND NECROSIS.
Chronic poisoning: (From inhalation or skin absorption.) Wt
loss, low blood pressure, jaundice, oliguria, or anemia may occur after repeated
minimal exposure.
Repeated contact with liquid can produce a dry, scaly,
fissured dermatitis. Liquid and vapor may also cause eye damage, including
corneal opacity. ... Acute exposures can lead to death from respiratory and
circulatory failure. Autopsies ... have revealed widespread bleeding and damage
in most internal organs.
IN CASES OF HUMAN POISONING BY 1,2-DICHLOROETHANE,
THE MAX ACTIVITY OF SERUM GLUTAMATE OXALACETATE TRANSAMINASE, GLUTAMATE
PYRUVATE TRANSAMINASE, AND GLUTAMATE DEHYDROGENASE WAS OBSERVED AFTER 5-8 DAYS,
AND IN 1 CASE AFTER 12 DAYS.
Agricultural workers received exposure dermally & via
inhalation (4-60 ppm) resulting from fumigation practices. 90 of 118 workers
reported symptoms including conjunctival congestion & burning sensation,
weakness, bronchial & pharyngeal symptoms, metalic taste in mouth, headache,
dermatographism, nausea, liver pain, tachycardia, & dyspnea after effort.
Liver function measurements showed abnormality in 40/56.
Aircraft industry workers using glue emitting 5-40 ppm ethylene
dichloride while drying were investigated over 5 years. Diseases of the
liver & bile ducts (19/83), neurotic conditions (13/89), autonomic dystonia
(11/83), asthenic conditions (5/89), & goiter & hyperthyroidism (10/89)
were revealed.
Intensification of light sensitivity due to exposure was
measured at concentrations of 1-12.5 ppm (4-50 mg/cu m). 1 ppm produced no
change in light sensitivity of the eye while at higher concentrations the
threshold of light perception decreased.
Circulatory changes after ingestion included a reduction in
clotting factors, platelet count, blood glucose levels, and albumin to globulin
ratio and an increase in fibrinolysis, prothrombin time, serum calcium, aldolase,
and bilirubin. Associated pathological changes included thrombi (pulmonary
arterioles and capillaries), hemorrhages (mucosa of esophagus, stomach, rectum
and cardiac tissue), overt bleeding into visceral organs and lungs, focal
hemorrhaging of the liver and kidney damage.
Ingestion of 1 or 2 oz, 400-800 mg/kg body weight, by an adult
male is fatal, deaths caused by circulatory or respiratory failure. The primary
target appears to be the central nervous system (CNS).
Neurotoxic effects: ... Mental confusion; vertigo; ...
functional nervous system changes; nervousness; insomnia; memory disorders;
tremor; nystagmus. /From table/
The cause-specific mortality of 2,510 males employed at an
east Texas chemical plant was examined in a historical prospective study to
evaluate a suspected incr in deaths from multiple myeloma & brain cancer.
Potential exposures from chemicals, either used in manufacturing processes or
produced during the study period 1952-1977, included the fuel additive
tetraethyl lead, ethylene dibromide, ethylene dichloride, inorganic
lead, & vinyl chloride monomer. Overall mortality for all workers (156
observed vs 211.14 expected) & for workers first employed between 1952 &
1959 (131 observed vs 167.33 expected) when tetraethyl lead was the single major
product was lower than expected when compared to the (USA) general population.
There were no significant increases in mortality from malignancies or other
causes of death. The deficits may be due to the small number of total deaths,
& the lower power for detecting excess risk of mortality from multiple
myeloma (zl-beta= 27, alpha= 0.05), brain cancer (zl-beta= 31, alpha= 0.05), or
other rare causes of death; lack of complete workplace exposure data for
production workers; & the absence of historical measurements on the extent
of environmental exposure. ...
1,2-Dichloroethane (EDC) and
1,2-dibromoethane (DBE) were tested for the ability to induce gene mutations in
2 human lymphoblastoid cell lines, designated AHH-1 and TK6. Both chemicals were
direct-acting mutagens in both cell lines. ... EDC was 25-fold more mutagenic in
the AHH-1 cell line than in the TK6 cell line. This differential sensitivity
between AHH-1 cells and TK6 cells was related to the levels of glutathione S-transferase
activity in these 2 cell lines.
Repeated skin contact should be avoided since the solvent can
cause defatting of the skin, severe irritation, and moderate edema. Eye contact
may have slight to severe effects.
WORKERS EXPOSED FULL-TIME TO CHEMICALS INCL ETHYLENE
DICHLORIDE IN PRODN OF ETHYLENE OXIDE SHOWED EXCESS MORTALITY FROM TUMORS
& DISEASES OF THE CIRCULATORY SYSTEM. ETHYLENE DICHLORIDE WAS
A PRIME SUSPECT.
Alpha-proteinase inhibitor can be inactivated by aldehydes
found in the cigarette smoke as well as by industrial chemicals. Studies
demonstrate the synergistic inactivation of alpha-proteinase inhibitor by 1,2-dichloroethane
when mixed with acrolein or pyruvic aldehyde. Smokers exposed to the
chemical may be more prone to lung emphysema due to synergistic inactivation of
alpha-proteinase inhibitor by chemicals and cigarette smoke components.
Three workers who spent about 4 hr washing yarn in an open vat
became dizzy & nauseated & vomited profusely. They complained of
weakness, trembling, & cramplike epigastic pain. When examined about an hr
after onset, all were still vomiting frequently, all had red macerated hands,
& least one had rales in lungs & a palpable liver. Partial recovery was
prompt, but occasional nausea persisted for several days. The men were
discharged in a wk but their hands healed only after several more weeks.
In man, death has resulted from the ingestion of 20 to 50 ml. Ethylene
dichloride is hepato- and nephro-toxic. Acute exposure also leads to
central nervous depression, reduced blood pressure, and cardiac impairment. In
humans, signs of intoxication are headache, nausea, vomiting, dizziness, watery
stool, internal bleeding, cyanosis, weak and rapid pulse and loss of
consciousness. In one human poisoning by ingestion, hypoglycemia, increased
clotting time and hypercalcemia were prominent laboratory findings. Symptoms
developed slowly; death occurred after six days. Extensive necrosis of liver,
kidney and adrenal glands was found at autopsy.
Fatal dichloromethane poisoning in 2 workers following
inhalation exposure was described. The 2 men (50 & 55 yr old) were employed
at an Italian chemical factory & were found dead in a 2 m deep well where
they had been burying barrels of chemical waste. The barrels contained mixed
solvent & solid wastes. On site air sampling found dichloromethane vapor
concns ranging up to 582 mg/l. Concns below 6 mg/l of 1
2-dichloroethane, l,l,l-trichloroethane & styrene were also detected.
Blood samples collected 24 hr after death contained 571.6 & 600.9 mg/l
dichloromethane. Smaller concns of 1,2-dichloroethane, 1,1,1-trichloroethane
& styrene were also found. Blood carboxyhemoglobin concns of 30% saturation
were also found. Autopsies revealed extensive brain & lung edema &
congestion gastric congestion & erosive multifocal gastritis in both
victims. Kidney congestion was manifested as tubular swelling &
degeneration, glomerular swelling & congestion of the vessels. Congestion
was also seen in the liver, spleen & adrenals. ... Both deaths were caused
by acute inhalation of extremely high dichloromethane vapor concns. ...
The United States National Toxicology Program lists ... 1,2-dichloroethane
/as a suspected carcinogen/. This category implies that these chemicals
may be reasonably anticipated to be carcinogens based on (1) evidence of
carcinogenicity from studies in humans that cannot exclude chance bias or
confounding but appear credible; or (2) sufficient evidence of carcinogenicity
from studies of animals which indicate an increased incidence of malignant
tumors (a) in multiple species or strains, (b) in multiple experiments, or (c)
to an unusual degree with regard to the incidence, site, or type of tumor.
Halogenated solvents tested during the 1800s for use as an
anesthetic & discarded included ... 1,2-dichloroethane (/caused/
excessive salivation, convulsive movements, postoperative blue-gray corneal
opacities)... .
Centrilobular hepatic necrosis has been observed in autopsy of
one case of a 51-yr old man who died following an inhalation exposure in a
confined space. This case was remarkable for the elevation of serum ammonia,
serum transaminase (SGOT, SGPT), lactate dehydrogenase (LDH), & creatine
kinase isoenzymes (MM-CPK). In addition, elevation of mitochondrial ornithine
carbonyl transferase (OCT) & mitochondrial glutonic oxaloacetic transaminase
was observed, which indicates that dichloroethane can cause mitochondrial
damage.
In a study of 278 men working in the chlorohydrin unit of a
chemical production plant between 1940-1967 & followed up to 1988, there was
a significant (p<0.01) excess of deaths due to pancreatic cancer compared to
the USA national rates [Standardized Mortality Ratio (SMR)= 492 (95%
CI=158-1140); Observed:Expected (O:E)= 8:16]. The excess was greater when
confined to men who worked in the unit for more than 2 yr (SMR= 800). Based on
comparison with 2 groups of workers in nearby plants, there were pronounced
increases in mortality due to pancreatic cancer as exposure duration increased.
Though an excess of deaths due to "lymphatic & hemopoietic
cancers" was also observed, it appeared to be attributable principally to
leukemia, for which numbers of observed cases were small (O=4) &
associations with duration of exposure were less consistent. ... The authors
concluded on the basis of considerable qualitative information that workers in
this unit had been exposed primarily to 1,2-dichloroethane in
combination with bis-chloroethyl ether, ethylene oxide & ethylene
chlorohydrin.
A 51-yr old man who inhaled a concentrated vapor of 1,2-dichloroethane
for only 30 min died 4 days later from cardiac arrhythmia ... . No
attempt was made to estimate the actual exposure concn. An autopsy revealed
congestion of the lungs, degenerative changes in the myocardium, liver necrosis,
renal tubular necrosis, and shrunken nerve cells in the brain.
... ingestion of large amt of 1,2-dichloroethane
may be lethal to humans. ... reported a case in which a 63-yr old man
accidentally swallowed approx 2 ounces (60 ml) of 1,2-dichloroethane
and died 22 hr later of circulatory failure. A 50-yr old man mistakenly
ingested approx 30 ml of 1,2-dichloroethane and died
after 10 hr ... . A 14-yr old boy died 6 days after ingesting 15 ml of
1,2-dichlorethane ... . A 30-yr old patient in a neuropsychiatric hospital
ingested approx 40 ml of 1,2-dichloroethane and died 28
hr later ... . ... reported a case of an 18-yr old man who because drowsy,
cyanotic, and exhibited bradycardia after drinking approx 50 ml of Marament
which is equivalent to 50 g of 1,2-dichloroethane (714
mg/kg/day); he died 17 hr later in a state of circulatory shock.
The respiratory effects exhibited by individuals who died
following acute oral exposure to 1,2-dichloroethane incl
congestion, pulmonary edema (at 570 mg/kg/day) and bronchitis ... .
Clinical investigation of patients who died following acute
ingestion of 1,2-dichloroethane determined that
cardiovascular insufficiency and hemorrhage were major factors contributing to
death ... .
GI symptoms have been observed in humans prior to death
following oral exposure to 570 or 714 mg/kg/day of 1,2-dichloroethane.
These symptoms incl nausea, vomiting, and diarrhea ... . Hemorrhagic
colitis, hemorrhagic gastritis, and focal hemorrhages of the GI tract have also
been reported upon autopsy ... .
1,2-Dichloroethane has been
implicated as a hepatotoxin humans after acute oral poisoning ... . Ingestion of
> or = 570 mg/kg/day of 1,2-dichloroethane resulted
in severe hepatocellular damage and liver atrophy ... and necrosis ... .
Acute renal damage resulting from ingestion of 1,2-dichloroethane
has been observed in humans. Ingestion of 714 mg/kg/day resulted in
bleeding and hyperemia of kidney in a 50-yr old man ... . In one case study,
renal damage that resulted from acute oral poisoning of a 25-yr old man was not
considered severe or permanent, and the patient fully recovered ... . The amt of
1,2-dichloroethane ingested was not reported. However,
individuals who died following ingestion of 15-30 ml of 1,2-dichloroethane
had severe kidney damage, primarily in the form of diffuse renal necrosis
... . These are only crude estimates of ingested dose.
Neurological effects, such as CNS depression, have been
reported in humans following acute oral intoxication with 1,2-dichloroethane
... . Morphological alterations in the nervous system were observed in
patients who died of acute oral poisoning by 1,2-dichloroethane.
These alterations incl vascular disorders, diffuse changes in cerebellar
cells, parenchymatous changes in brain and spinal cord, myelin degeneration, and
hyperemia and hemorrhage of the brain ... . The morphological changes observed
in the cerebellum may affect the coordination of muscular movements.
Human Toxicity Values:
The lethal oral dose of 1,2-dichloroethane in
humans has been estimated to be between 20-50 ml.
Skin, Eye and Respiratory Irritations:
Vapors are irritating.
Medical Surveillance:
Annual medical exams shall be made available to all workers
exposed to ethylene dichloride including medical and
work history and comprehensive medical exam with particular attention to
cardiovascular, pulmonary, neurological, liver and kidney functions. Records
will be maintained for 20 yrs /SRP: OSHA requires 30 years/ after termination of
employment.
PRECAUTIONS FOR "CARCINOGENS": Whenever medical
surveillance is indicated, in particular when exposure to a carcinogen has
occurred, ad hoc decisions should be taken concerning ... /cytogenetic and/or
other/ tests that might become useful or mandatory. /Chemical Carcinogens/
Preplacement physical examinations should focus on
establishing a baseline for kidney & cardiac function as well as detecting
preexisting conditions (arteriosclerotic heart disease, liver dysfunction,
chronic skin conditions, alcoholism) that may predispose the worker to toxic
effects of halogenated solvents. Periodic medical exams should be designed to
detect alterations in CNS function (e.g., impairment of perceptual speed,
reaction time, & manual dexterity), hepatic dysfunction, GI symptoms, &
dermatitis. The extent of routine laboratory analyses (serum hepatic
transaminases, urinalysis, serum creatinine) depends on the physician's judgment
of the severity of exposure based on workplace practice, environmental
monitoring, & biologic exposure limits. /Halogenated solvents/
The assessment of ethylene dichloride exposure
can be accomplished through measurement of ethylene
dichloride. However, this measurement should be performed shortly after
exposure, since ethylene dichloride is rapidly
eliminated form the body. In addition it is not possible from /Whole blood or
Urine/ measurement to assess the level of ethylene chloride to
which the person was exposed, due to the lack of reference ranges which
correlate with exposure levels.
Chest Radiography: Chest radiographs are widely used to assess
pulmonary disease. They are useful for detecting early lung cancer in
asymptomatic people, & especially for detecting peripheral tumors such as
adenocarcinomas. However, even though OSHA mandates this test for exposure to
some toxicants such asbestos, experts' views on the risk-to-benefit ratio in
detection of pulmonary disease conflict, so routine annual chest x-rays are not
recommended for all people.
Pulmonary Function Tests: The tests that have been found to be
practical for population monitoring include: Spirometry & expiratory
flow-volume curves; Determination of lung volumes; Diffusing capacity for carbon
monoxide; Single-breath nitrogen washout; Inhalation challenge tests; Serial
measurements of peak expiratory flow; Exercise testing.
Urine Albumin: Albuminuria has been shown to be a specific
marker of glomerular dysfunction. Tubular damage, however, can also result in
increased levels of albumin in the urine.
Urinary Beta-2-Microglobulin and/or Retinal Binding Protein:
Measurements for the presence of either of these low molecular weight proteins
are useful in detection of early impairment of proximal tubular function.
However, beta-2-microglobulin is unstable at urinary pH less than 6, and may
degrade in the bladder prior to collection and subsequent neutralization of the
urine sample. Measurement of retinal binding protein appears to be a better
marker for early tubular dysfunction due to its stability in the urine
subsequent to collection and analysis. However, retinal binding protein is
produced in the liver and not a constitutive protein of the kidney, so that its
presence in the kidney provides only indirect evidence of tubular damage.
Urinary Enzyme N-Acetylglucosaminidase: This lysosomal enzyme
has shown promise in assessment of subclinical nephrotoxic injury. This enzyme
is not normally filtered at the glomerulus due to its high molecular weight. In
the absence of glomerular injury, this enzyme will be detected in the urine as a
result of leakage or exocytosis from damaged, stimulated, or exfoliated renal
cells. The sensitivity of measurement for this enzyme has not been thoroughly
studied, but it's usefulness has shown some promise. However, this enzyme is
unstable at urinary pH >8, which could diminish the sensitivity of the
measurement due to enzyme degradation.
Routine Urinalysis: Performing a routine urinalysis including
parameters such as specific gravity, glucose, & microscopic exam may be
useful for assessing renal toxicity. Cylinduria, or formation of various types
of casts from material in the renal tubules, is detected only by microscopic
analysis, but is often preceded by albuminuria or increases in white cells, red
cells, or epithelial cells in the urine. Workers with potential exposure to
nephrotoxins should have baseline, pre-exposure measurements of the parameters
that will be selected for assessing early renal damage. Periodic measurement
should be compared to the baseline results. The normal progression of chronic
renal insufficiency usually takes several years to evolve, however
glomerulonephritis can occur as early as several months.
Liver Function Tests: Biochemical tests - Enzymes that reflect
cholestasis: alkaline phosphatase (AP), 5'-nucleotidase (5'-NT) & leucine
aminopeptidase (LAP); Enzymes that detect direct hepatic damage: aspartate
aminotransferase (AST), alanine aminotransferase (ALT) & gammma glutamyl
Transpeptidase (GGTP); Clearance tests - indocyanine green, antipyrine test
& serum bile acids.
Populations at Special Risk:
Nursing mothers should not be exposed to 1,2-dichloroethane.
Phenobarbital, which has been used widely for a number of
seizure disorders and as a soporific, is known to induce cytochrome P-450
activity and thus incr the rate of the first metabolic steps involved in 1,2-dichloroethane
metabolism ... . Thus, individuals taking phenobarbital are at greater
risk for experiencing 1,2-dichloroethane-induced
toxicity.
The synergistic effect of disulfiram ... on 1,2-dichloroethane
hepatotoxicity and carcinogenicity in animal studies suggests that
individuals exposed concurrently to 1,2-dichloroethane and
disulfiram, either in the rubber industry or medically ... have incr risk for
liver toxicity ... . Disulfiram and its reduced form diethyldithiocarbamate are
known inhibitors of microsomal MFO enzyme, particularly cytochrome P-450 2E1 ...
. It is possible that people exposed to other MFO inhibitors of like specificity
would be at similar risk.
Alpha-proteinase inhibitor can be inactivated by aldehydes
found in the cigarette smoke as well as by industrial chemicals. Studies
demonstrate the synergistic inactivation of alpha-proteinase inhibitor by 1,2-dichloroethane
when mixed with acrolein or pyruvic aldehyde. Smokers exposed to the
chemical may be more prone to lung emphysema due to synergistic inactivation of
alpha-proteinase inhibitor by chemicals and cigarette smoke components.
Probable Routes of Human Exposure:
... WORKERS PRIMARILY EXPOSED TO 1,2-DICHLOROETHANE
WERE THOSE IN HOSPITALS, BLAST FURNACES, STEEL MILLS AND AIR
TRANSPORTATION INDUSTRIES.
NIOSH (NOES Survey 1981-1983) has statistically estimated that
83,246 workers (33,361 of these are female) are potentially exposed to 1,2-dichloroethane
in the US(1). Occupational exposure to 1,2-dichloroethane
may occur through inhalation and dermal contact with this compound at
workplaces where 1,2-dichloroethane is produced or
used(SRC). Monitoring data indicate that the general population may be exposed
to 1,2-dichloroethane via inhalation of ambient air,
ingestion of food and drinking water, and dermal contact with this compound and
consumer products containing 1,2-dichloroethane(SRC). 5
of 1043 household products were found to contain 1,2-dichlroethane, a 0.5%
occurrence(2). These include automotive products (0.6% frequency, 0.1% w/w avg
concn), oils, greases and lubricants (2.6% frequency, 0.1% w/w avg concn), and
miscellaneous products (3.2% frequency, 0% w/w avg concn)(2). 12.5 million
people are estimated to be exposed to avg annual concn of 0.009-9 ppb near
production facilities(2). The exposure estimate from filling tank with gasoline
is 0.1 ug/day (time-weighted avg)(2).
Body Burden:
1,2-Dichloroethane was detected in
human breath of residents from Old Love Canal, Niagara Falls, NY at a concn of
0-54 parts/trillion, 4 of 9 samples pos and in urine at a concn of 0-140
parts/trillion, 3 of 9 samples pos(1). It was detected in mothers' milk of women
had occupational exposure of up to 14 ppm at a concn of 5.4-6.4 ppm immediately
after exposure(2).
Animal Toxicity Studies:
Toxicity Summary:
... The predominant source of exposure to 1,2-dichloroethane
by the general population is indoor and outdoor air, only minor amounts
being contributed by drinking water. Intake of 1,2-dichloroethane
from food is probably negligible. ... 1,2-dichloroethane
is readily absorbed following inhalation, ingestion or dermal exposure
and is rapidly and widely distributed throughout the body. It is rapidly and
extensively metabolized in rats and mice, with principally sulfur-containing
metabolites being eliminated in the urine in a dose-dependent manner. ... 1,2-Dichloroethane
appears to be metabolized via two principal pathways: the first involves
a saturable microsomal oxidation mediated by cytochrome P-450 to
2-chloroacetaldehyde and 2-chloroethanol followed by conjugation with
glutathione. The second pathway entails direct conjugation with glutathione to
form S-(2-chloroethyl)-glutathione, which may be nonenzymatically converted to a
glutathione episulfonium ion: this ion can form adducts with DNA. Although DNA
damage has been induced by the P-450 pathway in vitro, several lines of evidence
indicate that the glutathione conjugation pathway is probably of greater
significance than the P-450 pathway as the major route for DNA damage. ... The
acute toxicity of 1,2-dichloroethane is low in
experimental animals. ... The results of short-term and subchronic studies in
several species of experimental animals indicate that the liver and kidneys are
the target organs ... Morphological changes in the liver were observed in
several species following subchronic exposure to airborne concentrations ...
Increases in the relative liver weight have been observed in rats following
subchronic oral administration ... The carcinogenicity of 1,2-dichloroethane
has been investigated in a few limited bioassays on experimental animals
... Significant increases were not reported in the incidence of any type of
tumor in Sprague-Dawley rats or Swiss mice /by inhalation/ ... There was a
non-significant increase in the incidence of mammary gland adenomas and
fibroadenomas in female Sprague-Dawley rats exposed /by inhalation/ ... In
contrast, there was convincing evidence of increases in tumor incidence in two
species following ingestion. Significant increases in the incidence of tumors at
several sites (including squamous cell carcinomas of the stomach (males),
hemangiosarcomas (males and females), fibromas of the subcutaneous tissue
(males), adenocarcinomas and fibroadenomas of the mammary gland (females)) were
observed in Osborne-Mendel rats administered daily doses ... by gavage ...
Similar increases in the incidences of tumors at multiple sites (including
alveolar/bronchiolar adenomas (males and females), mammary gland adenocarcinomas
(females) and endometrial stromal polyp or endometrial stromal sarcoma combined
(females) and hepatocellular carcinomas (males)) occurred in B6C3F1 mice
administered daily doses ... by gavage ... The incidence of lung tumors (benign
papillomas) was significantly increased in female mice following repeated dermal
application of 1,2-dichloroethane ... Concomitant
exposure to inhaled 1,2-dichloroethane and disulfiram
in the diet resulted in an increased incidence of intrahepatic bile duct
cholangiomas and cysts, subcutaneous fibromas, hepatic neoplastic nodules,
interstitital cell tumors in the testes and mammary adenocarcinomas in rats,
compared to rats administered either compound alone or untreated controls. No
potential to initiate or promote tumor development was evident ... In in vitro
assays, 1,2-dichloroethane has been consistently
positive in mutagenicity bioassays in Salmonella typhimurium. In cultured
mammalian cells, 1,2-dichloroethane forms adducts with
DNA. It also induces unscheduled DNA synthesis in primary cultures of rodent and
human cells and gene mutation in several cell lines. Mutation frequency in human
cell lines has been correlated with differences in glutathione-S-transferase
activity. ... There is no evidence that 1,2-dichloroethane is
teratogenic in experimental animals. ... Acute incidental exposure to 1,2-dichloroethane
by inhalation or ingestion has resulted in a variety of effects in
humans, including effects on the central nervous system, liver, kidney, lung and
cardiovascular system. The potential carcinogenicity of 1,2-dichloroethane
in exposed human populations has not been extensively investigated. ...
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence in humans for the
carcinogenicity of 1,2-dichloroethane. There is
sufficient evidence in experimental animals for the carcinogenicity of 1,2-dichloroethane.
Overall evaluation: 1,2-Dichloroethane is
possibly carcinogenic to humans (Group 2B).
CLASSIFICATION: B2; probable human carcinogen. BASIS FOR
CLASSIFICATION: Based on the induction of several tumor types in rats and mice
treatd by gavage and lung papillomas in mice after topical application. HUMAN
CARCINOGENICITY DATA: None.
A4. Not classifiable as a human carcinogen.
Non-Human Toxicity Excerpts:
... Chronic toxicity of 1,2-dichloroethane /was
studied/ by exposing /rats, rabbits, guinea pigs, monkeys, dogs, & cats/ 7
hr/day, 5 days/wk to concn of 100-1000 ppm of the vapor in air. At a concn of
1000 ppm rats, rabbits, & guinea pigs died after a few 7 hr exposures. Dogs
& cats ... /were/ more resistant, but deaths eventually occurred.
Pathological exams of the various animals showed ... pulmonary congestion, renal
tubular degeneration, fatty degeneration of the liver, & less commonly,
necrosis & hemorrhage of the adrenal cortex & fatty infiltration of the
myocardium. ... Deaths occurred among guinea pigs, rabbits, & rats, although
some of the animals survived many exposures. Pathological exam revealed lesions
similar to those seen with 1000 ppm. A concn of 200 ppm was ... tolerated by 2
monkeys & 5 rabbits. ... When concn ... was lowered to 100 ppm, even rats,
guinea pigs & mice survived exposures for 4 mo & developed no
demonstrable lesions. A comparable chronic study was carried out /by others/ ...
/in/ animals /exposed/ 7 hr/day, 5 days/wk. They likewise showed high mortality
at 400 ppm in rats & guinea pigs in periods of 14 to 56 days of exposure.
The animals showed loss of weight & slight incr in weights of liver &
kidneys, but relatively slight histopathological changes. Guinea pigs showed
more definite histopathological changes in both the liver & kidneys.
GROUPS OF 50 MALE & 50 FEMALE 5 WK-OLD B6C3F1 MICE WERE
ADMIN TECHNICAL-GRADE 1,2-DICHLOROETHANE IN CORN OIL BY
GAVAGE ON 5 CONSECUTIVE DAYS/WK FOR 78 WK. ... THE TIME-WEIGHTED AVG DOSES WERE
195 AND 299 MG/KG BODY WT/DAY FOR HIGH-DOSE MALES AND FEMALES AND 97 AND 149
MG/KG BODY WT/DAY FOR LOW-DOSE MALES AND FEMALES. A GROUP OF 20 MALE AND 20
FEMALE MICE THAT RECEIVED CORN OIL ALONE SERVED AS MATCHED VEHICLE CONTROLS.
ANOTHER GROUP OF 60 MALE AND 60 FEMALE MICE THAT RECEIVED THE SAME VEHICLE
SERVED AS POOLED VEHICLE CONTROLS. OF THE HIGH-DOSE MALES, 50% SURVIVED AT LEAST
84 WK, & 42% SURVIVED UNTIL END OF STUDY; 72% (36/50) OF HIGH-DOSE FEMALE
MICE DIED BETWEEN WK 60 & 80. IN LOW-DOSE GROUPS, 52% (26/50) OF MALES
SURVIVED < 74 WK, & 68% (34/50) OF FEMALES SURVIVED UNTIL END OF STUDY.
IN VEHICLE CONTROL GROUPS, 55% (11/20) OF MALES & 80% (16/20) OF FEMALES
SURVIVED UNTIL END OF STUDY. ALMOST ALL ORGANS & ANY TISSUE CONTAINING
VISIBLE LESIONS WERE EXAM HISTOLOGICALLY. THE NUMBERS OF ANIMALS WITH TUMORS
& TOTAL NUMBER OF TUMORS WERE SIGNIFICANTLY GREATER IN MALE & FEMALE
MICE TREATED WITH THE HIGHER DOSE LEVEL, AND IN FEMALE MICE TREATED WITH THE LOW
DOSE, THAN IN CONTROLS. INCR INCIDENCE OF THE FOLLOWING NEOPLASMS WERE OBSERVED:
MAMMARY ADENOCARCINOMAS, UTERINE ADENOCARCINOMAS ENDOMETRIAL STROMAL NEOPLASMS
OF UTERUS & SQUAMOUS-CELL CARCINOMAS OF FORESTOMACH IN FEMALES; LUNG
ADENOMAS & MALIGNANT HISTIOCYTIC LYMPHOMAS IN MALES & FEMALES; AND
HEPATOCELLULAR CARCINOMAS IN MALE MICE.
1,2-Dichloroethane is mutagenic in
Salmonella typhimurium TA1530, TA1535, & TA100, presumably causing base-pair
substitution mutations; the mutagenic effect was enhanced by addition of cytosol
& glutathione. It was ineffective in inducing somatic crossing-over &
nondisjunction in Aspergillus nidulans.
GROUPS OF 50 MALE & 50 FEMALE OSBORNE MENDEL RATS, 9 WK
OLD, WERE ADMIN TECHNICAL-GRADE 1,2-DICHLOROETHANE IN
CORN OIL BY GAVAGE ON 5 CONSECUTIVE DAYS/WK FOR 78 WK. ... THE TIME-WEIGHTED AVG
DOSES WERE 95 & 47 MG/KG BW/DAY FOR HIGH- & LOW-DOSE MALES &
FEMALES. A GROUP OF 20 MALE & 20 FEMALE RATS RECEIVED CORN OIL ALONE &
WERE USED AS MATCHED VEHICLE CONTROLS; ANOTHER GROUP OF 60 MALE & 60 FEMALE
RATS RECEIVED THE SAME VEHICLE & WERE USED AS THE POOLED VEHICLE CONTROL
GROUP. THE LAST HIGH-DOSE MALE RAT DIED DURING WK 23 ... & THE LAST
HIGH-DOSE FEMALE RAT DIES DURING WK 15 OF THE OBSERVATION PERIOD. LOW-DOSE RATS
WERE OBSERVED FOR 32 WK AFTER ADMIN. MORTALITY WAS INCR IN HIGH-DOSE GROUPS: 50%
OF MALES WERE DEAD BY WK 55 & 50% OF FEMALES BY WK 57; BY WK 75, 84% OF
MALES & 80% OF FEMALES WERE DEAD. IN LOW-DOSE GROUP, 52% OF MALES SURVIVED
OVER 82 WK, & 50% OF FEMALES SURVIVED OVER 85 WK. ALL TREATED & CONTROL
ANIMALS WERE EXAM HISTOLOGICALLY. THE TOTAL NUMBER OF TUMORS WAS SIGNIFICANTLY
GREATER THAN THAT IN CONTROLS ONLY IN FEMALE RATS TREATED WITH HIGH DOSE;
HOWEVER, A SIGNIFICANT INCR IN NUMBER OF SQUAMOUS-CELL CARCINOMAS OF FORESTOMACH
IN MALE RATS & MAMMARY GLAND ADENOCARCINOMAS & FIBROADENOMAS IN FEMALE
RATS TREATED WITH THE HIGH DOSE WAS OBSERVED. ... A GROUP OF 20 MALE & 20
FEMALE UNTREATED MATCHED CONTROLS WAS INCL, BUT IT WAS NOT CONSIDERED IN
STATISTICAL ANALYSES OF TUMORS INCIDENCE.
... INCR IN MUTATION FREQUENCY /REPORTED/ IN BARLEY (HORDEUM
VULGARE) WHEN KERNELS WERE TREATED FOR 24 HR AT 20 DEG C WITH 30.3 MMOL 1,2-DICHLOROETHANE.
EXPOSURE OF VIRGIN DROSOPHILA MELANOGASTER FEMALES TO 1,2-DICHLOROETHANE
VAPORS IN AIR (7 MG IN A 1.5-L DESICCATOR FOR 4 OR 8 HR) LED TO AN INCR
IN FREQUENCY OF SEX-LINKED RECESSIVE LETHALS; INCR IN THE FREQUENCY OF
SEX-CHROMOSOME NON-DISJUNCTION WAS SEEN AFTER THE 8-HR TREATMENT.
MALE & FEMALE ICR SWISS MICE RECEIVED 1,2-DICHLOROETHANE
@ 0, 0.03, 0.09, OR 0.29 MG/ML IN WATER. NO DOSE-DEPENDENT EFFECTS ON
FERTILITY, GESTATION, VIABILITY, OR LACTATION INDICES WERE OBSERVED & THE
SURVIVAL OF PUPS & WT GAIN WERE NOT ADVERSELY AFFECTED.
WHEN HALOETHANES WERE BEING TESTED AS DIRECT-ACTING AGENTS IN
THE CHINESE HAMSTER OVARY CELL/HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE (CHO/HGPRT)
SYSTEM ETHYLENE BROMIDE EXHIBITED MORE CYTOTOXIC & MUTAGENIC ACTIVITY THAN ETHYLENE
DICHLORIDE & ETHYLENE BROMOCHLORIDE. ON A MOLAR BASIS, THE RELATIVE
ACTIVITY OF ETHYLENE BROMIDE : ETHYLENE BROMOCHLORIDE : ETHYLENE
DICHLORIDE WAS APPROX 100 : 6 : 1. CELL SURVIVAL WAS DECREASED TO 50% BY
APPROX 3, 6 & 50 MMOLES OF THESE COMPOUNDS RESPECTIVELY. WHEN THESE 3
HALOETHANES WERE ASSAYED IN PRESENCE OF S9 MIXTURE, THERE WAS 5-25-FOLD INCR IN
MUTAGENICITY; HOWEVER, ONLY ETHYLENE BROMOCHLORIDE & ETHYLENE
DICHLORIDE ALSO SHOWED CONCOMITANT INCR IN MUTAGENICITY OF 4-FOLD.
... 250 or 500 ppm /of 1,2-dichloroethane was
admin/ in feed mash to rats for 2 yr period. Approx 60-70% of the dose was
consumed. No significant decrease in fertility, litter size or fetal weight was
observed.
... Rats /were exposed/ to vapor at 100 & 300 ppm for 7 hr
daily during days 6-15 of gestation. Ten of the 16 rats at 300 ppm died &
only one rat had an implanted pregnancy with total resorption.
Harmful to plants, retarding growth & development along
with seedling development. Induces morphological & chlorophyll mutations,
resulting in necrosis & atrophy, in some cases.
1,2-Dichloroethane ... inhibited ...
growth of DNA polymerase-deficient /(pol I, pol A1-)/ Escherichia coli.
1,2-Dichloroethane produced
single-stranded breaks in DNA of hamster cells & chromosomal aberrations in
barley kernels.
The effects of 1,2-dibromoethane (DBE) & 1,2-dichloroethane
(EDC) on the incorporation of (3)H-thymidine into DNA were evaluated in
various tissues of mice. The cmpds were given ip 24 hr before sacrifice in an
equimolar dose (293 umol/kg). Two hr before the animals were killed, 0.5 nCi
(3)H-thymidine/g was injected ip. Both agents inhibited the (3)H-thymidine
incorporation in the forestomach, a site for their carcinogenic action. ... EDC
was inhibitory in the kidney. ...
... The present study examines the effect on liver tumor
incidence of continuous treatment of chloroform (CHCl3) (600 mg/l and 1800
mg/l), 1,1-dichloroethane (835 mg/l and 2500 mg/l), and 1,2-dichloroethane
(835 mg/l and 2500 mg/l) administered in drinking water to male B6C3F1
mice using a two-stage (initiation/promotion) treatment protocol. Seventy
4-week-old male B6C3F1 mice constituted each treatment group. Of these mice, 35
were initiated by treatment with diethylnitrosamine (10 mg/l) in the drinking
water for 4 weeks. The remaining 35 received deionized drinking water. Each
group was subsequently treated with one of two concentrations of chloroform,
1,1-dichloroethane or 1,2-dichloroethane in drinking
water for 52 weeks. An additional group received phenobarbital (500 mg/l) and
served as the positive control for liver tumor promotion. Mice sacrificed after
24 weeks (10 mice) and 52 weeks (25 mice). Liver and lung tumors were detected;
/however/, 1,1-dichloroethane, and 1,2-dichloroethane did
not affect the incidence or number of liver or lung tumors in the
diethylnitrosamine-initiated animals. ...
Liver tissue from rats administered 13 different alkyl halides
/including 1,2-dichloroethane/ and 4 other hepatotoxins
were assayed for indexes of hepatic heme synthesis. These included
aminolevulinic acid dehydratase activity, porphyrin content, and microsomal
cytochrome p450 and glutathione content. Consistent decreases in the dehydratase
activity and cytochrome p450 content were found. Significant changes in
glutathione and porphyrin content also occurred after exposure to some
compounds, but they were not consistent. ...
Eight chlorinated ethanes and 3 chlorinated ethylenes were
tested in the BALB/c-3T3 cell transformation assay. ... Chloroethane,
1,1-dichloroethane, and 1,2-dichloroethane, 1,1,1,2-tetrachloroethane
and 1,1,2,2-tetrachloroethane, hexachloroethane, and tetrachloroethylene were
all negative in the assay conducted in the absence of an exogenous metabolic
activation system. ...
The effects of food deprivation, carbohydrate restriction, and
ethanol consumption on the metabolism of 8 volatile hydrocarbons (benzene,
toluene, 1,2-dichloroethane, 1,1-dichloroethylene, and
trichloroethylene) in rats were compared with the effects of enzyme induction by
phenobarbital, polychlorinated biphenyls and 3-methylcholanthrene on the
metabolism of these compounds. Although causing a marked increase in microsomal
protein and cytochrome p450 contents, phenobarbital (80 mg/kg/day for 3 days)
and polychlorinated biphenyls (a single dose of 500 mg/kg) induced only a
limited range of enzyme activity. ... In contrast, food deprivation,
carbohydrate restriction, and 3 wk ingestion of ethanol (2.0 g/day) each
enhanced the metabolism of all the hydrocarbons with little or no increase in
microsomal protein and p450 contents. ...
Chloroacetaldehyde, a postulated metabolite of 1,2-dichloroethane,
is mutagenic in Salmonella typhimurium TA100. /Chloracetaldehyde/
1,2-DICHLOROETHANE GIVES A WEAK
DIRECT MUTAGENIC EFFECT IN SALMONELLA TYPHIMURIUM TA1535, WHICH IS ENHANCED BY
ADDITION OF RAT POSTMITOCHONDRIAL LIVER FRACTION (S-9). THIS ACTIVATION IS NADPH-INDEPENDENT
& NONMICROSOMAL. THIS ACTIVATION IS FURTHER ENHANCED BY ADDITION OF
GLUTATHIONE BUT NOT BY ADDN OF L-CYSTEINE, N-ACETYL-L-CYSTEINE OR
2-MERCAPTOETHANOL. ACTIVATION OF 1,2-DICHLOROETHANE WAS
ALSO FOUND IN THE PRESENCE OF GLUTATHIONE AND GLUTATHIONE S-TRANSFERASE A AND C
BUT NOT WITH GLUTATHIONE S-TRANSFERASE B. APPARENTLY 1,2-DICHLOROETHANE
IS ACTIVATED BY CONJUGATION WITH GLUTATHIONE.
Carbon tetrachloride and 1,2-dichloroethane were
added in vitro to freshly prepared slices of rat liver and the time and
concentration dependence of their toxic effects on several metabolic parameters
determined. With each agent, the most sensitive effect was an increase of
malondialdehyde production by a microsomal preparation isolated from the treated
slices. The next most sensitive parameter was the inhibition of amino acid
incorporation into slice proteins, followed by inhibition of net K+ accumulation
and the induction of early necrotic changes, as indicated by loss of
histological staining with azure II. Substantially greater exposures were
required to reduce cellular ATP and to initiate entry of Ca2+. This sequence was
similar with both agents, CCl4 was the more potent in each case. When added in
combinations of submaximally effective concentrations, the two agents produced
at least additive inhibition of protein synthesis and K+ accumulation. Amino
acid incorporation and K+ transport are the most convenient indicator systems.
In vivo sister chromatid exchange induced by 1,2-dichloroethane
was studied in bone marrow cells of mice after acute treatment for 24 hr.
With the exception of the lowest concentration (0.5 mg/kg), each series
exhibited a statistically significant increase in sister chromatid exchange.
The studies were designed to determine the early
histopathological effects of two known water contaminants, 1,2-dichloroethane
and 1,1-dichloroethylene, administered alone or in mixtures to laboratory
rats. Both agents cause cytotoxic responses in kidney and liver. Significant
changes were seen in cell, cytoplasmic and nuclear volumes, except in the high
dose 1,2-dichloroethane group (600 mg/kg). Comparison
of measured parameters of the single dosed animals with the mixed dosed
exhibited the most significant differences in the lipid droplet compartment.
The metab & binding of (14)C-labelled 1,2-dichloroethane
in female C57BL mice were studied. As shown by whole-body autoradiography
of iv injected mice, a selective localization of non-volatile & bound 1,2-dichloroethane
metabolites occurred in the nasal olfactory mucosa & the tracheo-bronchial
epithelium. Low levels of metabolites were also present in the epithelia of the
upper alimentary tract, vagina & eyelid, & in the liver & kidney. A
decreased mucosal & epithelial binding was observed after pretreatment with
metyrapone, indicating that the binding might be due to an oxidative metab of 1,2-dichloroethane.
The levels of in vivo binding were considerably lower in mice injected ip
with 1,2-dichloroethane as compared to mice given
equimolar doses of (14)C-labelled 1,2-dibromoethane. In vitro experiments with
1000g supernatants from various tissues showed that nasal mucosa has a marked
ability to activate 1,2-dichloroethane into products
that become irreversibly bound to the tissue. The nasal olfactory mucosa is a
target tissue for toxicity of 1,2-dichloroethane.
The transcriptional & replicative activities of hepatic
nuclei during DNA damage induced by 1,2-dichloroethane, a
hepatocarcinogen, were examined. DNA damage was measured by DNA alkylation in
rodents exposed to 1,2-dichloroethane. A time-dependent
DNA damage in vivo & in vitro was observed. A significant inhibition of RNA
synthesis was observed when transcription was carried out in vitro using nuclei
of 1,2-dichloroethane treated animal. The inhibition in
RNA synthesis persisted even when 50% of DNA damage was removed. Similarly,
nuclear DNA synthesis in vitro was also significantly inhibited during DNA
damage. However, DNA synthesis was recovered rapidly even though 50% of DNA
damage persisted. Results on the effect of alpha-amanition RNA synthesis that
50-70% of synthesis was carried out by RNA polymerase II.
Three chloromethanes and 8 chlorinated ethanes (/including/
1,1- and 1,2-dichloroethane, were assayed in tests for
the induction of mitotic segregation in Aspergillus nidulans diploid strain P1.
Eight of the 11 compounds assayed /including/ 1,1- and 1,2-dichloroethane,
significantly increased the frequency of morphologically abnormal
colonies which produced euploid whole-chromosome segregants (haploids and non-disjunctional
diploids). The induction of aneuploidy as the primary genetic event was provided
in haploid strain 35f with 1,2-dichloroethane. Lipophilicity,
known to be related to c-mitotic activity, did not show any significant
relationhip with aneuploidizing activity.
Chlorinated hydrocarbons found in a bioassay to be
carcinogenic to both B6C3F1 mice and Osborne-Mendel rats (1,2-dichloroethane),
carcinogenic only to mice (1,1,2-trichloroethane,
1,1,2,2-tetrachloroethane, hexachloroethane, trichloroethylene, and
tetrachloroethylene, and noncarcinogenic to either species (1,1-dichloroethane
and 1,1,1-trichloroethane) were used to investigate the biochemical bases for
tumorigenesis. Studies were conducted after chronic oral dosing of adult mice
and rats with the MTD and 1/4 MTD of each compound. ... Metabolism of the
compounds (nmoles per kg body weight) was 1.7 to 10 times greater in mice than
in rats. Hepatic protein binding (nanomole equivalents bound to 1 mg of liver
protein) was 1.2 to 8.3 times higher in mice than in rats except for 1,2-dichloroethane
and 1,1,1- trichloroethane. The noncarcinogens 1,1-dichloroethane and
1,1,1-trichloroethane exhibited 2 to 18 times more binding in mice than did the
carcinogens 1,2-dichloroethane and
1,1,2-trichloroethane. Urinary metabolite patterns of the compounds were similar
in both species. The biochemical parameters measured provided no clue to
differentiate the carcinogens from the noncarcinogens.
Five chlorinated aliphatics /including/ 1,1-dichloroethane and
1,2-dichloroethane were examined in a rat liver foci
assay for evidence of initiating and promoting potential. Young adult male
Osborne-Mendel rats (ten/group) were given partial hepatectomies, followed 24 hr
later by a single ip dose of either diethylnitrosamine (30 mg/kg body weight) or
chlorinated aliphatics, 1 wk later either a diet containing 0.05% (w/w)
phenobarbital or daily oral gavage five times weekly of chlorinated aliphatics
in corn oil for 7 weeks, and sacrificed 1 wk later. Putative preneoplastic
markers monitored were foci with increased gamma-glutamyltranspeptidase
activity. Chlorinated aliphatics were without significant effect in the
initiation protocol at the maximum tolerated dose. In the promotion protocol,
1,1-dichloroethane /but not 1,2-dichloroethane/ induced
significant increases in gamma-glutamyltranspeptidase activity (+) foci above
control levels. Two variants of gamma-glutamyltranspeptidase activity (+) foci
were distinguishable, one associated predominantly with phenobarbital promotion,
resembling preneoplastic foci in other models, and the other associated with
chlorinated aliphatics promotion, which was less intensely strained and
exhibited branching, resembling foci undergoing redifferentiation.
3 of 19 pregnant rabbits exposed to 300 ppm and 4 of the 21
rabbits exposed to 100 ppm died during the study. No pathological changes were
observed on gross necropsy. Reproduction was not affected in rats exposed to up
to 150 ppm 1,2-dichloroethane by inhalation 6 hr/day
for 176 days.
Corneal clouding is described in poisoned dogs, and several
species developed hemorrhagic /CNS depression/ of the adrenal cortex. In rats,
radiolabeled ethylene dichloride was excreted primarily
in the urine, and the major urinary metabolites were chloroacetic acid,
5-carboxymethyl cysteine, and thiodiacetic acid. Large doses of chloroacetic
acid are said to deplete liver glutathione stores, and 1,2-dichloroethane
may have a similar effect. Feeding studies have produced a variety of
malignant tumors in experimental animals.
1,2-Dichloroethane was not
teratogenic in rats inhaling 100 ppm or in rabbits inhaling 100 or 300 ppm for 7
hr/day throughout the period of major organogenesis. Of the 16 rats exposed to
300 ppm, 10 died, which demonstrates that the 300 ppm exposure concentration was
maternally toxic. Symptoms which preceded death included lethargy, ataxia,
decreases in body weight and food consumption and vaginal bleeding.
1,2-Dichloroethane was reported to be
carcinogenic in rats in a long term bioassay using gavage in corn oil (24 &
48 mg/kg/day, but not by inhalation (up to 150-250 ppm, 7 hr day, 5 days/wk).
The daily dose metabolized was similar in the 2 experiments. In order to address
this discrepancy, the genotoxicity of 1,2-dichloroethane was
investigated in vivo under different exposure conditions. Female F344 rats
(183-188 g) were exposed to 1,2-(14)-C-dichloroethane in a closed inhalation
chamber to either a low, constant concn (0.3 mg/l= 80 ppm for 4 hr) or to a peak
concn (0.3 mg/l= 80 ppm for 4 hr) or to a peak concn (up to 18 mg/l= 4400 ppm)
for a few minutes. After 12 hr in the chamber, the dose metabolized under the
two conditions was 34 mg/kg & 140 mg/kg. DNA was isolated from liver &
lung & was purified to constant specific radioactivity. DNA was
enzymatically hydrolyzed to the 3'-nucleotides which were separated by reverse
phase HPLC. Most radioactivity eluted without detectable or with little optical
density, indicating that the major part of the DNA radioactivity was due to
covalent binding of the test compound. ...
Thirteen week studies were conducted to investigate potential
differences in rat strain susceptibility to 1,2-dichloroethane
toxicity. F344/N rats, Sprague-Dawley rats, Osborne-Mendel rats and
B6C3F1 mice (10 animals of each sex) were exposed to 1,2-dichloroethane
in drinking water at 0, 500, 1,000, 2,000, 4,000 or 8,000 ppm for 13
weeks. No compound related deaths occurred in any of the rat strains exposed to 1,2-dichloroethane
in drinking water. Weight gain depression was common in each sex of all
three rat strains in the 4,000 and 8,000 ppm groups throughout the studies.
Water consumption was decreased by 50%-60% with increasing dose for all exposed
male and female rats regardless of strain. Kidney and liver weights were
increased in dosed rats of all three strains. No chemical-related lesions were
observed except for a dose related incidence of renal tubular regeneration in
female F344/N rats. Nine of 10 female mice exposed to 8,000 ppm 1,2-dichloroethane
in drinking water died before the end of the study. Mean body weights of
males at 500 ppm or more and females at 1,000 ppm or more were lower than those
of controls throughout most of the studies. Kidney weights were significantly
increased for dosed males and females. 1,2-Dichloroethane admin
in drinking water resulted in less toxicity to F344/N rats than admin of similar
doses by gavage.
In dogs, investigators have found fairly consistently that in
ten to fifteen hours after systemic administration of 1,2
dichloroethane, either by inhalation or subcutaneous injection, both
corneas begin to become blue gray and swollen. Clouding increases to a maximum
about two to three days after the intoxication, then subsides in the course of
several days to several months, depending on the severity.
... Rats, guinea pigs, rabbits, and cats tolerated 6 hr daily
exposures to 500 ppm 5 days/week for 13 weeks with no adverse effect. Rats,
guinea pigs, and rabbits also tolerated injury and increased blood urea. Rats,
guinea pigs, and rabbits also tolerated an additional 13 weeks at 1000 ppm but
cats showed histological evidence of kidney injury and increased blood urea.
Adult male Sprague Dawley rats were given single doses of 0,
0.5, 1.0, 2.0, 4.0, & 8.0 g/kg in corn oil. There was significant mortality
only at 8 g/kg & no evidence of treatment-related effects on serum or
urinary enzyme levels, organ weights, or tissue morphology. Rats received
repeated oral doses of 0, 0.5, 1.0, 2.0, or 4.0 g/kg 5 days/wk for 12 wks. There
was marked CNS depression & high mortality only in the 4 g/kg group but
little evidence of toxicity other than transient CNS depression at lower levels.
Marked fatty degeneration in monkeys was demonstrated at 400
ppm for 8-12 days.
... The relative susceptibility of 3 strains of rats (F344/N,
Sprague-Dawley & Osborne-Mendel) & 1 strain of mice (B6C3F1), exposed to
1,2-dichloroethane in drinking-water at concns of up to
8000 mg/l for 13 wks, & one of the same strains or rats (F344/N) exposed to
doses of up to 480 mg/kg bw/day by gavage in corn oil for 13 wks, was
investigated. Based on increased relative organ weights, the liver & kidneys
were the target organs in both rats & mice, although treatment-related
microscopic lesions were noted only in female F344/N rats & B6C3F1 mice.
Admin of 1,2-dichloroethane to F344/N rats by gavage
resulted in more severe toxic effects (including death) than admin of similar
doses in drinking-water, probably due to greater peak levels of the cmpd in the
blood, & saturation of elimination mechanisms. The authors considered the
NOEL for 1,2-dichloroethane admin to F344/N rats by
gavage to be 120 & 150 mg/kg bw/day in males & females, respectively,
based on mortality & chemically related lesions in the forestomach. The NOEL
of B6C3F1 mice exposed via drinking-water was considered to be 780 mg/kg bw/day
(2000 ppm) in males, based on kidney lesions, & 2500 mg/kg bw/day (4000 ppm)
in females, based on mortality. The authors did not consider the doses to which
the 3 strains of rats were exposed in the drinking-water to be high enough to
result in biologically significant toxic effect, although alterations were
observed at doses as low as 49-82 mg/kg bw/day in some strains (i.e. Sprague-Dawley
& Osborne-Mendel).
In a 10 day toxicity study, Sprague Dawley rats of each sex
were given 1,2-dichloroethane at dose levels of 10, 30,
100 or 300 mg/kg body weight per day by gavage. Although 8/10 males and all
females in the high-dose group died, no hematological or clinical chemical
changes were observed. The only histopathological effect was a slight
inflammation of the forestomach in the 100 mg/kg body weight group. In a 90 day
study at dose levels of 37.5, 75 and 150 mg/kg body weight per day, no treatment
related effect on mortality or gross histopathology was observed.
In a teratology study, rats and rabbits were exposed to 100 or
300 ppm (400 or 1200 mg/cu m) 1,2-dichloroethane for 7
hours per day on days 6 through 15 (rats) or 6 through 18 Rabbits) of gestation.
In rats, 10/16 dams died at the high dose, one exhibited implantation sites but
all the implantantations were resorbed. At 100 ppm, 1,2-dichloroethane
was not overtly toxic to the dam and did not induce fetotoxicity,
teratogenicity or skeletal variations with the exception of a decrease in the
number of bilobed thoracic centra. In rabbits, 3/19 dams died at the high dose;
there were no adverse effects on fetal or embryonal development.
Acute exposure (< or = 14 days) /via inhalation/ resulted
in death in rats and guinea pigs at 400 ppm and in mice, rabbits, and dogs at
1500 ppm. These were the lowest exposure conc that produced death in animals.
Gross observations at necropsy revealed liver and kidney effects ranging from
incr organ weight to necrosis, pulmonary congestion, and fatty infiltration and
degeneration of the myocardium ... .
Intermediate-duration exposure (6-25 wk) /via inhalation/
resulted in death in rats and guinea pigs exposed to 200 ppm, rabbits exposed to
400 ppm, and dogs, cats, and monkeys exposed to 1000 ppm ... . Necropsy of these
animals revealed effects on the liver, kidnye, heart, and lungs similar to those
observed following acute exposure. In a chronic inhalation study, survival of
rats intermittently exposed to 50 ppm of 1,2-dichloroethane for
2 yr was similar to controls ... .
In animals, acute exposure to high concn of 1,2-dichloroethane
/via inhalation/ was also assoc with pulmonary congestion. A single 7-hr
exposure to 3,000 ppm ... produced death assoc with pulmonary congestion in
mice, rats, rabbits, and guinea pigs ... . Lower concn ... did not produce lung
lesions.
Acute lethal concentrations /via inhalation/ produced
myocarditis in rats, dogs, and monkeys ... . Guinea pigs that died following
intermittent exposure to > or = 200 ppm for 25 wk had fatty infiltration and
degeneration of the heart ... . Among animals that survived
intermediate-duration exposure ... cardiac changes were observed only in
monkeys.
In animals studies, GI effects, incl emesis and passing of red
watery stools, preceded death in dogs intermittently exposed to 1,500 ppm of 1,2-dichloroethane
for 6 days ... . Congestion of the GI tract was noted in these animals at
necropsy.
There are also reports of hepatic effects in animals following
acute-duration inhalation exposure to 1,2-dichloroethane. Serum
levels of enzymes used as indicators of hepatic damage ... were significantly
elevated in rats exposed to > or = 850 ppm for 4 hr ... . No effect was seen
at 618 ppm. ... Monkeys intermittently exposed to 400 ppm for 8-12 days had
marked fatty degeneration of the liver ... . Monkeys exposed to 100 ppm did not
show this effect. Slight parenchymatous degradation of the liver was found in
guinea pigs exposed to 400 ppm for < or = 14 days ... . ... Longer-term
exposure to 1,2-dichloroethane vapor produced hepatic
effects in guinea pigs, dogs, and monkeys. Guinea pigs intermittently exposed to
100 ppm ... for 246 days exhibited incr liver weight and hepatic fatty
infiltration ... . Monkeys exposed to 200 ppm for 25 wk and dogs exposed to 400
ppm for 8 mo also exhibited fatty degeneration of the liver ... . However, no
hepatic effects were observed upon gross and microscopic exam in mice, rats, or
rabbits intermittently exposed to concn of 100-400 ppm for 4-30 wk ... .
Acute-duration inhalation exposure to 1,2-
dichloroethane also produced renal effects in animals. Cloudy swelling of
the renal tubular epithelium and incr kidney weight were reported in guinea
pigs, and degeneration of the tubular epithelium was reported in monkeys
following intermittent exposure to 400 ppm for 8-12 days ... . ... Kidney
lesions have also been reported following longer-term exposure of animals ... .
Dogs intermittently exposed to 400 ppm for 8 mo exhibited fatty changes in the
kidney ... . In guinea pigs, degeneration of the kidney was observed but only at
lethal concn ... . Renal effects were not detected in rats, mice, guinea pigs,
or rabbits intermittently exposed to 100-400 ppm ... for 4-30 wk ... .
In animals there is evidence that exposure to
1,2-dichlorethane affects the ability to fight infection arising from inhaled
microbial pathogens. Female mice exposed to 5-11 ppm ... for 3 hr exhibited incr
susceptibility to Streptococcus zooepidemicus (i.e., incr mortality following
infection), suggesting reduced pulmonary defenses in the exposed mice ... . No
effect was observed at 2.3 ppm. Also in this study, high-dose mice had reduced
bactericidal activity in the lungs 3 hr after exposure to Klebsiella pneumoniae
... . Male rats exposed to 200 ppm for 5 hr or 100 ppm 5 hr/day for 12 days did
not exhibit any incr susceptibility to infection from these microbes ... .
Acute-duration exposure to concentrated 1,2-dichloroethane
also produced neurological effects in animals. Rats exposed to > or =
12,000 ppm for 30 min experienced CNS depression ... . Exposure to 20,000 ppm
for 15 min resulted in CNS depression sufficient to cause death; no
histopathology was conducted ... . Tremors, uncertain gait, and narcosis were
seen in rats, guinea pigs, and rabbits exposed to 3,000 ppm for 7 hr ... .
Longer-term exposure to lower concn ... did not appear to produce neurological
effects, although sensitive indicators of subtle neurological effects were not
examined.
Intermittent exposure of female rats /via inhalation/ to 4.7 +
or - 7 ppm for 4 mo prior to the mating period, followed by inhalation exposure
during pregnancy, produced a statistically significant (p<0.01) incr in
embryo mortality ... . In an earlier study ... reported decr fertility in rats
exposed to 14 ppm ... for 6 mo. No adverse effects on the fertility, gestation,
or survival of pups were observed in male or female rats exposed to 1,2-dichloroethane
concn of < or = 150 ppm in a one-generation reproduction study ... .
1,2-Dichloroethane has produced
genotoxic effects in animals following inhalation exposure. Inhalation of 1,000
ppm ... vapors for 4 hr produced irreversible deoxyribonucleic acid (DNA) damage
as evidenced by single-stranded breaks in mouse hepatocytes. This genetic damage
was seen at a concn that produced mortality in 80-100% of treated mice within 24
hr ... . In a study investigating the relationship between inhalation exposure
... and covalent binding to liver and lung DNA, female Fischer-344 rats were
exposed either to 80 ppm ... for 4 hrs ("constant-low" exposure) or
4,400 ppm for a few minutes ("peak" exposure) ... . The DNA covalent
binding index was elevated, compared to controls, after both exposure scenarios.
However, in both the liver and the lung the effect was much greater (approx 35
times greater) after peak exposure ... .
Evidence from animal studies suggests that the immune system
is a target of 1,2-dichloroethane after oral exposure.
In mice exposed for 14 days by gavage to 4.9 and 49 mg/kg/day, there was a
significant dose-related reduction in humoral immunity (measured by
immunoglobulin M(IgM) response to sheep erythrocytes), and a significant but not
dose-related, reduction in cell-mediated immunity (measured by delayed-type
hypersensitivity response to sheep erythrocytes) ... . In mice give 49
mg/kg/day, these effects wee accompanied by a 30% decr in total leukocyte
number.
Neurological effects have also been observed in animals
exposed to 1,2-dichloroethane by ingestion. Clinical
signs in rats exposed to > or = 240 mg/kg/day by gavage for < or = 13 wk
incl tremors, salivation, emaciation, abnormal posture, ruffled fur, and dyspnea
... . Upon microscopic exam, mild necrotic lesions were observed in the
cerebellum of rats dosed with 240 or 300 mg/kg/day.
Oral exposure to 1,2-dichloroethane has
produced genotoxic effects in animals. A single oral dose of 100 mg/kg of 1,2-dichloroethane
produced irreversible DNA damage, as revealed by single-stranged breaks
in the hepatocytes of mice ... . A single oral dose of 150 mg/kg produced high
levels of DNA binding in the liver of rats ... . The level of binding produced
was similar in rats that had previously been exposed via inhalation to 50 ppm
... vapor for 2 yr, and in rats that had served as controls in the 2-yr study.
Results of these studies indicate that 1,2-dichloroethane
is carcinogenic in rats by the oral route, with a gavage dose > or =
47 mg/kg/day, producing tumors at locations remote from the site of admin ... .
Statistically significant incr in multiple tumor types (malignant and benign)
were noted in treated animals of both species. An incr incidence of fibromas of
the sc tissue and hemangiosarcomas of the spleen, liver, pancreas, and adrenal
gland (as well as other organs and tissues) occurred in male rats of both
exposure groups (47 and 95 mg/kg/day). In the high-dose group (95 mg/kg/day),
male rats had incr squamous cell carcinomas of the forestomach, and female rats
had incr frequencies of adenocarcinomas and fibroadenomas of the mammary gland.
In mice, the incidence of hepatocellular carcinomas and pulmonary adenomas incr
in males given 195 mg/kg/day. In female mice from both the 149- and
299-mg/kg/day exposure groups, there were incr incidences of pulmonary adenomas,
adenocarcinomas of the mammary gland, and endometrial polyps and sarcomas.
The carcinogenicity of 1,2-dichloroethane following
dermal exposure has been evaluated in mice ... . In this study, a statistically
significant incr in pulmonary papillomas was observed in mice treated with 126
mg ... three times/wk for 428-576 days. These results, which indicate a
significant incr in benign tumors remote from the site of application, provide
suggestive or supportive evidence that 1,2-dichloroethane is
carcinogenic and that it can penetrate through the skin into the circulatory
system.
... Prior to exposure to ethylene dichloride
(EDC) groups of male mice were pretreated with phenobarbital or
3-methylcholanthrene to induce metabolism. Other mice were administered SKF525A
before ethylene dichloride exposure to inhibit
cytochrome p450 metabolism. Following the different pretreatments, mice were
exposed to ethylene dichloride at selected
concentrations (1000, 1250, or 1500 ppm). Exposure to ethylene
dichloride, without pretreatment, produced a dose-dependent increase in
mortality at 24 and 48 hr postexposure. This response was enhanced at all
concentrations of EDC by phenobarbital pretreatment and attenuated by the
administration of SKF 525A. Pretreatment with 3-methylcholanthrene prior to ethylene
dichloride exposure at 1000 ppm also produced an increase in mortality as
compared to ethylene dichloride exposure without
pretreatment. Exposure to ethylene dichloride was
associated with an increased kidney wt/body wt ratio. SKF 525A pretreatment
prevented the increase in the kidney wt/body wt ratio at an ethylene
dichloride exposure concn of 1000 ppm. Pathological changes produced in
the kidneys of mice exposed to ethylene dichloride were
decreased by SKF 525A pretreatment.
National Toxicology Program Studies:
A bioassay of technical grade 1,2-dichloroethane
for possible carcinogenicity was conducted using Osborne-Mendel rats and
B6C3F1 mice. 1,2-Dichloroethane in corn oil was admin
by gavage, at either of two dosages, to groups of 50 male and 50 female animals
of each species. The 78 wk period of chem admin was followed by an observation
period of 32 wk for the low dose rats of both sexes. The last high dose male rat
died after 23 wk of observation and the last high dose female rat died after 15
wk of observation. All treated groups of mice were observed for an additional 12
or 13 wk following chem admin. Initial dosage levels for the chronic bioassay
were selected on the basis of a preliminary subchronic toxicity test. Subsequent
dosage adjustments were made during the course of the chronic bioassay. The time
weighted avg high and low doses of 1,2-dichloroethane in
the chronic study were 95 and 47 mg/kg/day, respectively, for rats of both
sexes. The high and low time weighted avg doses for the male mice were 195 and
97 mg/kg/day, respectively, and 299 and 149 mg/kg/day, respectively, for the
female mice. For each species, 20 animals of each sex were placed on test as
vehicle controls. These animals were gavaged with corn oil at the same times
that dosed animals were gavaged with 1,2-dichloroethane mixtures.
Twenty animals of each sex were placed on test as untreated controls for each
species. These animals were not intubated. A statistically significant positive
association between dosage and the incidence of squamous cell carcinomas of the
forestomach and hemangiosarcomas of the circulatory system occurred in the male
rats, but not in the females. There was also a significantly incr incidence of
adenocarcinomas of the mammary gland in female rats. The incidences of mammary
adenocarcinomas in female mice were statistically significant. There was a
statistically significant positive association between chemical admin and the
combined incidences of endometrial stromal polyps and endometrial stromal
sarcomas in female mice. The incidence of alveolar/bronchiolar adenomas in both
male and female mice was also statistically significant. Under the conditions of
this study, 1,2-dichloroethane was carcinogenic to
Osborne-Mendel rats, causing squamous cell carcinomas of the forestomach,
hemangiosarcomas, and subcutaneous fibromas in male rats and causing mammary
adenocarcinomas in female rats. This cmpd was also found to be carcinogenic to
B6C3F1 mice, causing mammary adenocarcinomas and endometrial tumors in female
mice, and causing alveolar/bronchiolar adenomas in mice of both sexes. Levels of
Evidence of Carcinogenicity: Male Rats: Positive; Female Rats: Positive; Male
Mice: Positive; Female Mice: Positive.
Non-Human Toxicity Values:
LD50 Mouse oral 870-950 mg/kg
LD50 Rabbit oral 860-970 mg/kg
LD50 Rabbit percutaneous 3400-4460 mg/kg
LD50 Rat oral 670-890 mg/kg
LC50 Rat inhalation 12000 ppm/31.8 min, 3000 ppm/165 min, 1000
ppm/432 min
LD50 Mouse ip 370 mg/kg
LD50 Rat sc 700 mg/kg
LD50 Rat inhalation 1000 ppm/ 7 hr
LD50 Rat ip 807 mg/kg
LD50 Dog oral 5700 mg/kg
LC50 Rat inhalation 6600 mg/cu m/6 hr /From table/
LD50 Female mouse oral 413 mg/kg
LD50 Male mouse oral 489 mg/kg
Ecotoxicity Values:
LC50 Daphnia magna (water flea) 218,000 ug/l 48 hr.
/Conditions of bioassay not specified/
LC50 Mysid shrimp 113,000 ug/l/96 hr in salt water.
/Conditions of bioassay not specified/
LC50 GAMMARUS FASCIATUS (SCUD) GREATER THAN 100 MG/L/96 HR @
21 DEG C, AGE MATURE, STATIC BIOASSAY.
LC50 PTERONARCYS (STONEFLY) GREATER THAN 100 MG/L/96 HR @ 15
DEG C, SECOND YEAR CLASS, STATIC BIOASSAY.
LC50 SALMO GAIRDNERI (RAINBOW TROUT) 225 MG/L/96 HR @ 13 DEG
C, WT 1.8 G, STATIC BIOASSAY.
LC50 LEPOMIS MACROCHIRUS (BLUEGILL) 430 MG/L/96 HR (95%
CONFIDENCE LIMIT 230-710 MG/L), STATIC BIOASSAY, TEMP 21-23 DEG C, PH 7.9-6.5.
LC50 LEPOMIS MACROCHIRUS (BLUEGILL) > 600 MG/L/24 HR,
STATIC BIOASSAY, TEMP 21-23 DEG C, PH 7.9-6.5.
LC50 CYPRINODON VARIEGATUS (SHEEPSHEAD MINNOWS) > 130 PPM
BUT < 230 PPM @ 24 HR, 48 HR, 72 HR & 96 HR, STATIC TESTS, TEMP 25-31 DEG
C.
LC50 Pimephales promelas (fathead minnow) 136 mg/l/96 hr (95%
confidence limit: 129-144 mg/l), temp 25 deg C, dissolved oxygen 7.8 mg/l, water
hardness 44.8 mg/l calcium carbonate (CaCO3), alkalinity 41.4 mg/l CaCO3, pH
7.41, static bioassay. (Test 1)
LC50 Crangon crangon (brown shrimp) 75 mg/l/24 hr, 65 mg/l/48
hr, 65 mg/l/96 hr, + or - 2000 mg/l @ 3 min, + or - 630 mg/l/9 min, 345 mg/l/1
hr in sea water @ 15 deg C. /Conditions of bioassay not specified/
LC50 Gobius minutus (gobi) 185 mg/l/60 min, 3 hr & up to
96 hr in sea water @ 15 deg C. /Conditions of bioassay not specified/
LC50 Poecilia reticulata (guppy) 106 ppm/7 days. /Conditions
of bioassay not specified/
Toxicity threshold (cell multiplication inhibition test):
bacteria (Pseudomonas putida): 135 mg/l. Algae (Microcystis aeruginosa): 105
mg/l. Green algae (Scenedesmus quadricuda): 719 mg/l. Protozoa (Entosiphon
sulcatum): 1127 mg/l.
TSCA Test Submissions:
The ability of 1,2-dichloroethane to
induce morphological transformation in the BALB/3T3 mouse cell line (Cell
Transformation Assay) was evaluated. Based on preliminary clonal toxicity
determinations exposure time=1 day), 1,2-dichloroethane was
tested at 0, 4, 20, 100 and 250 ug/ml in one experiment and 5, 10, 25 and 50 ug/ml
in a second experiment, with cell survival ranging from 159% to 70% and from 98%
to 90% relative to controls, respectively. None of the tested concentrations
produced significantly greater transformation frequencies compared to untreated
controls.
The effects of 1,2-dichloroethane were
examined in the mouse hepatocyte primary culture/DNA repair test. Based on
preliminary toxicity tests, 1,2-dichloroethane was
tested at concentrations of 1, 0.1, 0.01, 0.001, 1x10(-4), 1x10(-5), 1x10(-6)
and 1x10(-7)% in DMSO solvent. The highest two concentrations were too cytotoxic
to be evaluated in the assay. The lower concentrations were not cytotoxic but
all these concentrations caused a significant increase in the unscheduled DNA
synthesis over the solvent control (DMSO).
The effects of 1,2-dichloroethane were
examined in the rat hepatocyte primary culture DNA repair assay. Based on
preliminary toxicity tests, 1,2-dichloroethane was
tested at concentrations of 1, 0.1, 0.01, 0.001, 1x10(-4), 1x10(-5) and
1x10(-6)% in DMSO solvent vehicle. The highest two concentrations were too
cytotoxic to be evaluated in the assay. The lower concentrations were not
cytotoxic but the 0.01, 0.001 and 1x10(-4)% levels caused a significant increase
in the unscheduled DNA synthesis over the solvent control (DMSO).
The mutagenicity of 1,2-dichloroethane was
evaluated in Salmonella tester strains TA98, TA100, TA1535 and TA1537 (Ames
Test), both in the presence and absence of added metabolic activation by Aroclor-induced
rat liver S9 fraction. 1,2-Dichloroethane caused a
positive response in strains TA100 and TA1535, both in the presence and absence
of added metabolic activation. 1,2-Dichloroethane did
not cause a positive response in strains TA98 or TA1537 in any of the tests. 1,2-Dichloroethane
was evaluated using a protocol in which the test article was usually
tested over a minimum of 6 dose levels, the highest nontoxic dose level being 10
mg/plate unless solubility, mutagenicity or toxicity dictated a lower limit.
In a one-generation reproduction study, male and female
Sprague Dawley rats (F0, 20/treated group, 30 in control group) were exposed to 1,2-dichloroethane
by inhalation at nominal doses of 25, 75 or 150 ppm for 6 hrs/day, 5
days/week for 12 weeks. The animals within each group were then bred
successively to produce F1a and F1b litters. Exposure of F0 animals increased to
7 days/week during mating, gestation and lactation. Litters were sacrificed at
21 days of age and F0 animals were then sacrificed. There were no significant
differences observed between treated and control animals in the following:
parental and fetal body weights, reproduction, fertility, external or internal
fetal anomalies, fetal or parental organ weights, gross necropsy findings, or
histological observations.
The effect of 1,2-dichloroethane was
examined in a mouse hepatocyte primary culture/DNA repair assay. The test
article was administered to B6C3F1 mouse liver hepatocytes at concentrations
ranging from 1x10E-7 to 1%, for 18 to 20 hours. A dose related increase in net
nuclear grain counts was observed, ranging from 9.4 at 1x10E-7% to 232.4 at
1x10E-2%. At exposure levels greater than 1x10E-2% 1,2-dichloroethane
was toxic to cells.
The effect of 1,2-dichloroethane was
examined in the rat hepatocyte primary culture/DNA repair assay. The test
article was administered under liquid exposure conditions to Osborne Mendell rat
liver hepatocytes at concentrations ranging from 1x10E-6 to 1%, for 18 to 20
hours. A dose related increase in net nuclear grain counts was observed, ranging
from 5.5 at 1x10E-4% to 120.1 at 1x10E-2%. At exposure levels greater than
1x10E-2% 1,2-dichloroethane was toxic to cells.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
THE METABOLITE, CHLOROETHANOL, WAS DETECTED IN BLOOD &
LIVER OF RATS DURING THE 1ST 2 DAYS AFTER INGESTION OF 750 MG/KG OF 1,2-DICHLOROETHANE.
FOLLOWING IP INJECTION OF 50-170 MG/KG BODY WT (14)C-1,2-DICHLOROETHANE
TO MICE, 10-42% WAS EXPIRED UNCHANGED AND 12-15% AS CARBON DIOXIDE,
DEPENDING ON DOSE; MOST OF REMAINDER WAS EXCRETED IN URINE, PRIMARILY AS
CHLOROACETIC ACID, S-CARBOXYMETHYLCYSTEINE AND THIODIACETIC ACID. THE METABOLISM
OF 1,2-DICHLOROETHANE TO CHLOROACETIC ACID PROCEEDS
POSSIBLY VIA CHLOROACETALDEHYDE TO 2-CHLOROETHANOL.
... (14)C-ETHYLENE DICHLORIDE /WAS
ADMIN/ TO MALE OSBORNE-MENDEL RATS BY GAVAGE (150 MG/KG IN CORN OIL) OR
INHALATION (150 PPM, 6 HR). ... THE MAJOR URINARY METABOLITES, THIODIACETIC ACID
AND THIODIACETIC ACID SULFOXIDE WERE IDENTIFIED, SUGGESTING A ROLE FOR
GLUTATHIONE IN BIOTRANSFORMATION OF ETHYLENE DICHLORIDE.
Metabolites (mammalian) of 1,2-dichloroethane
include: glycolic acid, oxalic acid, carbon dioxide, and
S,S-ethylene-bis-cysteine.
1,2-(14)C-Dichloroethane was metabolized by rat hepatic
microsomes to products that irreversibly bound polynucleotides. The
polynucleotides were enzymatically hydrolyzed and the products separated by a
high-performance liquid chromatography (HPLC) equipped with an ODS or a SCX
column. The products of microsome-mediated binding were identified in the high
performance liquid chromatography eluate as 1-N6-ethanoadenosine to polyadenylic
acid, 3,N4-ethanocytidine to polycytidylic acid, and 2 cyclic derivatives to
polyguanylic acid, 1,2-(14)C-dichloroethane was also metabolized in the presence
of a glutathione (GSH)-cytosolic fraction and a polynucleotide. After enzymatic
hydrolysis of the polynucleotide, the major peak of radioactivity was eluted
from a Sephadex G-25 column in the salt volume which excluded the presence of a
product containing glutathione and a nucleoside. Chromatography by ODS-High
performance liquid chromatography of the major peak from Sephadex G-25 indicated
the presence of a glutathione metabolite of 1,2-dichloroethane
that did not contain a nucleoside. A similar hydrophilic peak was
obtained for the hydrolysis products of polynucleotides from a glutathione plus
cytosol incubation in which the polynucleotide instead of being added prior to
the incubation was added after the incubation. The products of the
glutathione-cytosol metabolism of 1,2-(14)C-dichloroethane appeared to be
glutathione metabolites that coisolated with the polynucleotides rather than
covalently bound adducts. Covalently bound adducts were identified for microsome-mediated
binding of 1,2-dichloroethane to polynucleotides. ...
Male mice were pretreated with piperonyl butoxide (PIB), an
inhibitor of microsomal oxidative metabolism, and the effect of this
pretreatment on the extent of hepatic DNA damage produced by 1,2-dichloroethane
(EDC) was determined 4 hr after EDC administration. The in vivo
genotoxicity of 2-chloroethanol a product of the microsomal oxidative metabolism
of EDC, was also investigated. Hepatic DNA damage was measured with a sensitive,
alkaline DNA unwinding assay for the presence of single-strand breaks and
alkali-labile lesions in DNA. Pretreatment of mice with piperonyl butoxide to
inhibit microsomal oxidative metabolism significantly potentiated the hepatic
DNA damage observed 4 hr after a single, 200 mg/kg, ip dose of EDC. Treatment of
mice with single, ip doses of 2-chloroethanol as high as 1.2 mmol/kg failed to
produce any evidence of single-strand breaks and(or) alkali-labile lesions in
hepatic DNA. When 6-di-ethyl maleate (DEM) was used to deplete hepatic
glutathione levels prior to administration of 2-chloroethanol, the acute
hepatotoxicity of 2-chloroethanol was potentiated. ...
... Aryl halides were bound mainly to liver DNA whereas
interaction of alkyl halides with DNA of liver, kidney, and lung gave rise to
similar binding extent. In vitro activation of all chemicals was mediated by
microsomal p450-dependent mixed function oxidase system which is present in rat
and mouse liver and, in smaller amount, in mouse lung. Activation of alkyl
halides by liver cytosolic glutathione transferases also occurred. The relative
reactivity of chemicals in vivo, expressed as Covalent Binding Index (CBI) to
rat liver DNA, was: 1,2-dibromoethane > bromobenzene > 1,2-dichloroethane
> chlorobenzene > epichlorohydrin > benzene. ...
1,2-Dichloroethane is carcinogenic to
both B6C3F1 mice and Osborne-Mendel rats. ... Studies were conducted after
chronic oral dosing of adult mice and rats with the maximum tolerated dose (MTD)
and 1/4 maximum tolerated dose of each cmpd. The extent to which the cmpd were
metabolized in 48 hr, hepatic protein binding, and urinary metabolite patterns
were exam. Metabolism of the compounds (mmoles/kg) was 1.7-10 times greater in
mice than in rats. Hepatic protein binding (nm equiv bound to 1 mg of liver
protein) was 1.2-8.3 times higher in rats than in mice for 1,2-dichloroethane.
... Urinary metabolite patterns were similar in both species. ...
STIMULATION OF HEPATIC MICROSOMAL CARBON MONOXIDE-INHIBITABLE
NADPH OXIDN BY 1,2-DICHLOROETHANE WAS ENHANCED BY
INDUCTION WITH PHENOBARBITAL BUT NOT WITH BETA-NAPHTHOFLAVONE. INCUBATION OF
DICHLOROETHANES WITH HEPATIC MICROSOMES FROM PHENOBARBITAL-TREATED RATS, NADPH-GENERATING
SYSTEM, AND EDTA RESULTED IN THE CONVERSION OF 1,2-DICHLOROETHANE
TO CHLOROACETALDEHYDE AND TO A LESSER EXTENT TO CHLOROACETIC ACID AND
PROBABLY 2-CHLOROETHANOL. THE OMISSION OF DICHLOROETHANE OR THE NADPH-GENERATING
SYSTEM FROM INCUBATION MIXTURES ELIMINATED THESE EFFECTS. SKF-525A AND CARBON
MONOXIDE DIMINISHED OR ELIMINATED EFFECTS.
Ethylene dichloride is metabolized by
two competing pathways both of which consume glutathione. Ethylene
dichloride undergoes oxidation to form chloroacetaldehyde which is
detoxified by glutathione and also reacts directly with glutathione to form
2-(s-chloroethyl)-glutathione. A mathematical model for describing tissue
glutathione depletion and resynthesis after ethylene
dichloride exposure was developed. The reaction of glutathione with ethylene
dichloride and chloroacetaldehyde was simulated. Predicted values for the
glutathione content of the liver, lung, forestomach, or glandular stomach were
compared with experimental data obtained in male Fischer 344 rats and B6C3F1
mice dosed with 25 or 150 mg/kg ethylene dichloride. The
predicted values agreed with the experimental data. Of the tissues modeled, the
liver showed the greatest capacity for rapidly resynthesizing glutathione after
it was depleted by ethylene dichloride. In rats, liver
glutathione synthesis increased rapidly and rebounded past the preexposure
concentration 12 hr after exposure. The other tissue showed a much slower rate
of glutathione resynthesis. Similar results were seen for mouse liver ad lung
glutathione concentrations.
The metabolism of 1,2-dichloroethane is
mediated by enzymes located in the microsomal and cytosolic fraction of the
liver. The microsomal pathway is mediated by cytochrome p450 and quantitatively
more important in terms of both total metabolism and irreversible binding of
1,2-(14)C-dichloroethane to proteins. The cytosolic pathway is mediated by
glutathione transferase and is responsible for the mutagenicity of
1,2-(14)C-dichloroethane and for its binding DNA. The absorption and metabolism
of inhaled 1,2-dichloroethane was enhanced in rats
pretreated with phenobarbital, a classical inducer of cytochrome p450 and of
drug metabolism.
A study was conducted of the use of freshly isolated
hepatocytes to investigate the utilization of glutathione (GSH) in
1,2-dihaloethane metabolism. 1,2-Dichloroethane, 1,2-dibromoethane,
and 1-bromo-2-chloroethane were metabolized to S-(2-hydroxyethyl)glutathione),
S-(carboxymethyl)glutathione, and S,S -(1,2-ethanediyl)bis(glutathione).
1,2-Dihaloethane induced glutathione depletion was characterized and found to be
concomitant with the formation of at least three glutathione containing
1,2-dihaloethane derived metabolites and extensive protein covalent binding. The
formation of these glutathione containing metabolites accounted for 58%, 84%,
and 71% of the 1,2-dichloroethane, 1-bromo-2-chloroethane,
and 1,2-dibromoethane induced loss of intracellular glutathione, respectively.
Within 2.0 hours of incubation, the covalent binding of 1,2-dibromoethane to
hepatocyte protein reached 18.7 umol/ml of cell suspension. Half of this
covalent binding occurred within 0.5 hours of incubation in the presence of high
levels of intracellular glutathione. ...
1,2-Dichloroethane is readily
metabolized in the body. The primary metabolic pathways for this chemical are
mixed function oxidation (MFO) and glutathione conjugation. Oxidation products
incl chloroacetaldehyde, 2-chloroethanol, and 2-chloroacetic acid. MFO
metabolism of 1,2-dichloroethane appears to be
saturable at oral gavage doses of > or = 25 mg/kg and inhalation concn of
> or = 150 ppm (approx 500 mg/kg), both of which correspond to blood levels
of 5-10 ug/ml. Glutathione conjugation becomes relatively more important at
larger doses, and incr metabolism by this pathway may be responsible for the
toxic effects noted at these high doses.
Absorption, Distribution & Excretion:
... ETHYLENE DICHLORIDE IS READILY
ABSORBED VIA THE LUNG WHEN BREATHED OR VIA THE GI TRACT WHEN TAKEN BY MOUTH. TO
A LESSER EXTENT, IT IS ABSORBED THROUGH THE SKIN.
The effect of the pretreatment of male Sprague-Dawley rats
with phenobarbital, butylated hydroxyanisole & disulfiram on the inhalation
kinetics of 1,2-dichloroethane was studied by the gas
uptake method. ... The rate curves in all the pretreatment regimens showed
saturable dependence on 1,2-dichloroethane concn. These
saturable dependencies (Michaelis-Menten) appeared to be associated with
enzymatic metab. In general, a two-compartment, steady-state pharmacokinetic
model described the uptake data. Data were transformed by Hanes plots to
calculate the inhalational Km, the ambient 1,2-dichloroethane concn
at which uptake proceeded at half maximum rate, & Vmax, the maximum rate of
uptake (ie, maximum rate of metab). Although phenobarbital & butylated
hydroxyanisole pretreatments did not affect the Km of 1,2-dichloroethane,
phenobarbital pretreatment increased the Vmax while disulfiram
pretreatment decreased both the Km & Vmax.
The levels of 1,2-dichloroethane (1,2-EDC),
& its metabolites 2-chloroethanol, monochloroacetic acid, &
2-chloroacetaldehyde were determined by gas chromatography in the organs of
human cadavers in cases of acute poisoning. The highest 1,2-dichloroethane
levels were observed in the stomach & omentum; lower levels in the
kidney, spleen, brain, heart, large & small intestines, & blood, &
no detectable amounts in the liver. 2-Chloroethanol & monochloroacetic acid,
minor metabolites of 1,2-dichloroethane, were detected
in small amounts in the myocardium, brain, stomach, & small intestine.
2-Chloroacetaldehyde, because it is a reactive intermediate in the
biotransformation of 1,2-dichloroethane was not
detectable in the organs. The administration of acetylcysteine to acutely
intoxicated humans showed no positive clinical effect. ...
... (14)C-ETHYLENE DICHLORIDE /WAS
ADMIN/ TO MALE OSBORNE-MENDEL RATS BY GAVAGE (150 MG/KG IN CORN OIL) OR
INHALATION (150 PPM, 6 HR) ... APPROX 85% OF THE TOTAL METABOLITES APPEAR IN THE
URINE, WITH 7-8%, 4%, & 2% FOUND IN THE CARBON DIOXIDE, CARCASS, &
FECES, RESPECTIVELY, FOLLOWING EACH ROUTE OF ADMIN.
Urinary excretion of thiodiglycolic acid and thioethers after 1
2-dichloroethane dosing was studied in rats. Male Sprague-Dawley rats
were admin 0, 0.12, 0.25, 0.50, 1.01, 2.02, 4.04 or 8.08 uM/kg (14)C labeled 1,2-dichloroethane
orally. Urine samples were collected for 24 hours and analyzed for
thiodiglycolic acid and thioethers before and after alkaline hydrolysis by gas
chromatography and the Ellman reagent/absorption spectrophotometry (thioether
assay), respectively. The amounts of 1,2-dichloroethane derived
radioactivity excreted decreased as a logarithmic function of increasing 1,2-dichloroethane
dose ranging from 62.1% of the dose for 0.12 and 0.25 umol/kg 1,2-dichloroethane
to 7.4% of the 8.08 umol/kg dose. The concentratlons of urinary
thiodiglycolic acid were well correlated with 1,2-dichloroethane
dose up to 2.02 umol/kg. When expressed as a percentage of the dose
urinary excretion of thiodiglycolic acid was not dependent on the dose over the
range 0.12 to l.0l umol/kg 1,2-dichloroethane and
amounted to 21.8% of the dose. Before alkaline hydrolysis no thioethers could be
detected. After alkaline hydrolysis, urinary excretion of thioethers by rats
dosed with 0.12 and 0.25 umol/kg did not differ significantly from the control
value. Between 0.25 and 4.04 umol/kg 1,2-dichloroethane, thioether
excretion increased linearly with dose. The highest thioether/thiodiglycolic
ratio 0.17 occurred ln rats given 8.08 umol/kg 1,2-dichloroethane.
Urinary thiodiglycolic acid concentrations were not altered by alkaline
hydrolysis. The /results suggest/ that urinary thiodiglycolic acid excretion
correlates well with the oral dose of 1,2-dichloroethane in
rats. Urinary thiodiglycolic acid excretion may be a useful marker of 1,2-dichloroethane
exposure. Thiodiglycolic acid is hydrolyzed under alkaline conditions.
The thioether assay is not appropriate for estimating urinary thiodiglycolic
acid excretion.
Dichloroethane is readily absorbed from the GI &
respiratory tracts. Blood 1,2-dichloroethane levels
plateau in the rat at 8.3 ug/ml after a 2-3 hr exposure at 150 ppm. Steady-state
blood concns in the rat increased exponentially as the exposure concn increased;
after 6 hr of exposure at 50, 150, & 250 ppm, blood 1,2-dichloroethane
levels were 14, 8.3, & 31.3 ug/ml, respectively. During a 6 hr, 150
ppm exposure, the rats were calculated to have absorbed 113 mg 1,2-dichloroethane/kg,
or about 70% of the 1,2-dichloroethane they would have
inhaled if the minute ventilation was 0.76 liter/min/kg bw. 1,2-Dichloroethane
was rapidly cleared form the blood ... even following oral doses (<50
mg/kg) & inhalation exposure (<150 ppm)that result in nonlinear kinetics.
Urine was the principal route of elimination; approx 85% of the radioactivity
recovered following an oral exposure to 150 mg/kg or a 6-hr inhalation exposure
to 150 ppm of 1,2-[C14]dichloroethane, was excreted in the urine as thiodiacetic
acid & thiodiacetic acid sulfoxide. Anther 29% of the oral dose, but only
1.8% of the inhaled 1,2-[C14]dichloroethane, was excreted unchanged via the
lungs.
The rate of dermal absorption of 1,2-dichloroethane
by mice was 479.3 +or- 38.3 nmol/min/sq cm following covered application
of 0.5 ml of the undiluted solvent, while the rate of absorption of 1,2-dichloroethane
in 0.9% NaCl in vitro in excised skin of rats was 169 +or- 0.44 nmoles/min/sq
cm. Dermal absorption of 1,2-dichloroethane in aqueous
soln (1000 mg/l) was found to be similar in human & rat epidermis in vitro
within 1 hr of occluded application (20.3 ug/sq cm/hr versus 33.1 ug/sq cm/hr),
whereas when the substance was applied neat (uncovered), absorption within the
first 15 min was approx 4-10 fold greater in the rat epidermis than in the human
epidermis. In addition, absorption increased with applied dose in the rat
epidermis, whereas absorption was not dependent upon dose in the human
epidermis.
1,2-Dichloroethane has been detected
in the breast milk of women occupationally exposed via inhalation & dermal
contact.
The rate of elimination following oral (gavage) admin or
inhalation was such that 1,2-dichloroethane was not
detected in the blood a few hr after exposure & only small amounts were
detected in tissues (liver, kidney, lung, spleen, forestomach, stomach &
carcass) 48 hr after exposure ... . The rate of elimination from blood &
tissues appeared to depend on the exposure level; the higher the exposure level,
the lower the elimination rate of 1,2-dichloroethane, after
both oral & inhalation exposure. Elimination from the liver was reported to
be biphasic, a higher elimination rate occurring just after the peak levels of 1,2-dichloroethane
were reached. Elimination from other organs was monophasic. Following
inhalation up to an exposure level of 1012 mg/cu m, elimination was slowest in
adipose tissue & most rapid in the lung.
The % of admin radioactivity excreted in the urine over a 24
hr period in rats decreased with increasing single doses (0.25-8.08 mmol 1,2-dichloroethane/kg
bw) admin by gavage in mineral oil. The authors attributed these results to
saturation of metabolism rather than kidney damage, as there were no variations
in biochemical parameters of nephrotoxicity between the controls & groups
exposed to doses up to 4.04 mmol/kg bw. Urinary thiodiglycolic acid increased as
a linear function of the dose of 1,2-dichloroethane until
at least 1.01 mmol/kg bw; it accounted for 63% of the total metabolites in urine
at this dose.
Although 1,2-dichloroethane is
eliminated more slowly from adipose tissue than from blood or other tissues
(lung and liver) following exposure, it is unlikely to bioaccumulate, as no
significant difference was observed between levels in blood or tissues following
single or repeated (10 days) oral doses of 50 mg/kg body weight in rats.
1,2-Dichloroethane is well absorbed
through the lungs following inhalation exposure, the GI tract following oral
exposure, and the skin following dermal exposure in humans. In animal studies,
equilibrium blood concn of 1,2-dichloroethane were
obtained 2-3 hr after inhalation exposure, 15-60 min after oral exposure, and
1-2 hr after aqueous dermal exposure. Absorption probably occurs by passive
diffusion for all three routes of exposure. Upon absorption, 1,2-dichloroethane
is widely distributed within the body. Experiments in animals exposed
orally or by inhalation showed that the highest concn of 1,2-dichloroethane
(7-17 times that of the blood) were found in adipose tissue. The liver
and lung contained lower equilibrium levels of 1,2-dichloroethane
than the blood.
Excretion of 1,2-dichloroethane and
metabolites is rapid; in animal studies, excretion was essentially complete 48
hr after acute exposure. Following inhalation exposure to labeled 1,2-dichloroethane,
excretion of 1,2-dichloroethane was primarily in
the form of metabolites (thiodiglycolic acid and thiodiglycolic acid sulfoxide)
in the urine (84%), and as carbon dioxide (CO2) in the exhaled air (7%).
Following oral exposure to labeled 1,2-dichloroethane, the
amt of radioactivity excreted by these routes was reduced, and a large
percentage of the dose (29%) was excreted as unchanged 1,2-dichloroethane
in the exhaled air. The incr exhalation of unchanged 1,2-dichloroethane
may reflect the saturation of biotransformation enzymes.
Mechanism of Action:
The mechanism of the hepatocellular toxicity of
l,2-dichloroethane ... was examined in vitro. Hepatocytes from male Wistar rats
were preloaded with tritium (3)H labeled sodium palmitate and (14)C labeled
glucosamine. They were incubated with 0 to 6.5 uM 1,2-dichloroethane
for 5 to 60 min. Cytotoxicity was assessed by measuring changes in
cellular exclusion of trypan blue dye leakage of intracellular lactate
dehydrogenase (LDH) into the medium and depletion of intracellular reduced
glutathione (GSH). The cells were separated into the cytosolic microsome total
Golgi apparatus and secreted lipoglycoprotein fractions which were assayed for
changes in the distribution of (3)H and (14)C activity. 1,2-Dichloroethane
did not significantly affect cellular trypan blue exclusion and LDH
leakage until after 30 and 15 min incubation respectively. Hepatocellular GSH
concentrations were significantly decreased after 5 min. Incubation with 4.4 uM 1,2-dichloroethane.
1,2-Dichloroethane large decrease in lipoglycoprotein secretion which was
accompanied by significant accumulations of (3)H and (14)C activity in the
cells. The levels of (3)H and (14)C activity were significantly increased in the
microsomes and Golgi apparatus after 5 and 15 min of 1,2-dichloroethane
treatment. Within the lipoglycoprotein fraction 1,2-dichloroethane
significantly decreased the amounts of radiolabel in the lipid and sugar
moieties. ...
DNA sequence changes produced by 1,2-dibromoethane, 1,2-dichloroethane
and 1-bromo-2-chloroethane were analyzed using the vermilion locus of
Drosophila melanogaster. Under excision repair proficient (exr+) conditions (mutagenized
exr+ males mated with exr+ females) all mutants isolated from the first
generation (Fl) after 1,2-dibromoethane and 1,2-dichloroethane
exposure represented rearrangements (multi-locus deletions, small
deletions with tandem repeats, duplicate insertions). By contrast mutants
expressing a vermilion phenotype only in the F2 (Fl mosaics) all carried single
bp changes. When exr+ males after exposure to 1,2-dibromoethane were mated to
excision repair deficient (exr-) mus 201 females 11 of 14 mutational events
isolated from either Fl or F2 progeny were single bp changes. In general the
mutation spectra for the three dihaloalkanes were similar to the spectrum
obtained at the same locus for the direct acting monofunctional agent
methylmethanesulfonate. The data lend support to the conclusions that these
1,2-dihaloalkanes are genotoxic through modification at ring nitrogens in DNA
primarily at the N7 of guanine and, lesser extent, at the N1 of adenine. These
N-adducts could be directly miscoding. However, more important for the mutagenic
action of chemicals seems to be the formation of non-coding lesions and/or
misrepair.
The mechanism of action for 1,2-dichloroethane-induced
toxicity is not known. However, studies in rats and mice indicate that 1,2-dichloroethane
may be metabolized to 2-chloroacetaldehyde, S-(2-chloroethyl)glutathione,
and other putative reactive intermediates capable of binding covalently to
cellular macromolecules ... . The ability of a chemical to bind covalently to
cellular macromolecules is often correlated with the induction of toxic effects
... . In addition, 1,2-dichloroethane has been shown to
promote lipid peroxidation in vitro ... . Lipid peroxidation is also assoc with
production of tissue damage. The lag time between inhalation exposure and onset
of effects ... in an occupationally exposed 51-yr old male may have been a
reflection, in part, of the time required to metabolize 1,2-dichloroethane
to active intermediates.
Interactions:
The synergistic hepatotoxicity of dietary disulfiram (DSF)
with 1,2-dichloroethane (EDC) subchronically
administered by inhalation at three concentration levels (150, 300, and 450 ppm)
was studied. The criteria for hepatotoxicity were treatment related increases in
serum activities of sorbitol dehydrogenase, 5'-nucleotidase, and alkaline
phosphatase, and in liver-to-body weight ratios. Dietary disulfiram alone did
not elicit these responses while 1,2-dichloroethane at
the highest concentration level increased liver-to-body weight ratios and the
activity of 5'-nucleotidase. Exposure to dietary disulfiram alone decreased
cytochrome p450 levels, but in combination with 1,2-dichloroethane,
the decrement of cytochrome p450 was additive in a 1,2-dichloroethane
concn dependent manner. However, depression of cytochrome p450 by 1,2-dichloroethane
alone was not concentration dependent. Although dietary disulfiram and
dietary disulfiram/1,2-dichloroethane combination
increased the activity of glutathione S-transferases (GSTs), both dietary
disulfiram and 1,2-dichloroethane singly and in
combination increased the tissue levels of reduced glutathione (GSH).
The interaction of 1,2-dichloroethane with
disulfiram or ethanol was investigated in rats. Sprague-Dawley rats were exposed
for 24 months to 50 ppm concns of 1,2-dichloroethane in
an inhalation study while at the same time being exposed to 0.05% disulfiram in
the diet &/or 5% ethanol in the drinking water. A high incidence of
intrahepatic bile duct cholangioma were reported in both sexes receiving 1,2-dichloroethane
& disulfiram, 18% incidence among males & 34% among females. Male
rats also registered 12% incidence of hepatocellular adenomas, 22% incidence for
interstitial cell tumors in the testes, 20% subcutis fibroma, & 25% mammary
adenocarcinomas in females. The expected rates for these disorders would have
been 0, 4, 4, & 8%, respectively. A slight increase in neoplastic nodules
occurred in males receiving 1,2-dichloroethane &
ethanol, 8% versus 0% expected. The DNA binding by 1,2-dichloroethane
was not altered by disulfiram treatment, & the metab of 1,2-dichloroethane
was qualitatively the same as in corresponding controls. However, the
combined treatment of 1,2-dichloroethane &
disulfiram did reduce the rate of elimination of 1,2-dichloroethane,
& sustained the blood concn levels of unchanged 1,2-dichloroethane,
which may be related to the increased carcinogenic effect of the
combination.
The in vitro metabolism of 1,2-dichloroethane
by liver homogenates of rats admin ethanol increased with the dose of
ethanol up to 4 g/kg bw, but declined sharply at 5 g/kg bw.
High doses (1000-2000 mg/kg bw) of several chemicals,
including methionine, p-aminobenzoic acid, sulfanilamide & aniline, admin
orally to mice were protective against the lethal effects caused by inhalation
of 1600 mg/cu m (400 ppm) 1,2-dichloroethane.
The acute & subacute toxicity of dichloroethane increased
when it was administered under conditions of high temperature ... .
Induction of hepatic cytochrome P-450 enzymes by phenobarbital
and/or Aroclor 1254 incr the rate of MFO /mixed function oxidation/ metabolism
of 1,2-dichloroethane in vitro ... . Alterations in
metabolism could potentially produce profound effects on toxicity. Enhanced
enzymatic metabolism of 1,2-dichloroethane also occurs
after treatment with ethanol in vitro ... . Ethanol is an inducer of cytochrome
P-450 2E1, the primary MFO enzyme involved in 1,2-dichloroethane
metabolism ... .
Concurrent admin of 0.15% disulfiram in the diet and inhaled 1,2-dichloroethane
(10, 153-304, 455 ppm) in animals markedly incr hepatotoxicity much more
than would occur with exposure to 1,2-dichloroethane alone
... . Similarly, after chronic cotreatment with 50 ppm of 1,2-dichloroethane
by inhalation and 0.05% disulfiram in the diet for 2 yr, a series of
neoplastic lesions were produced in rats that were not produced by 1,2-dichloroethane
(or disulfiram) alone ... . The lesions included intrahepatic bile duct
cholangiomas, sc fibromas, hepatic neoplastic nodules, interstitial cell tumors
in the testes, and mammary adenocarcinomas.
Pharmacology:
Therapeutic Uses:
As a general anesthetic instead of chloroform, especially in
ophthalmic surgery. /Former use/
Interactions:
The synergistic hepatotoxicity of dietary disulfiram (DSF)
with 1,2-dichloroethane (EDC) subchronically
administered by inhalation at three concentration levels (150, 300, and 450 ppm)
was studied. The criteria for hepatotoxicity were treatment related increases in
serum activities of sorbitol dehydrogenase, 5'-nucleotidase, and alkaline
phosphatase, and in liver-to-body weight ratios. Dietary disulfiram alone did
not elicit these responses while 1,2-dichloroethane at
the highest concentration level increased liver-to-body weight ratios and the
activity of 5'-nucleotidase. Exposure to dietary disulfiram alone decreased
cytochrome p450 levels, but in combination with 1,2-dichloroethane,
the decrement of cytochrome p450 was additive in a 1,2-dichloroethane
concn dependent manner. However, depression of cytochrome p450 by 1,2-dichloroethane
alone was not concentration dependent. Although dietary disulfiram and
dietary disulfiram/1,2-dichloroethane combination
increased the activity of glutathione S-transferases (GSTs), both dietary
disulfiram and 1,2-dichloroethane singly and in
combination increased the tissue levels of reduced glutathione (GSH).
The interaction of 1,2-dichloroethane with
disulfiram or ethanol was investigated in rats. Sprague-Dawley rats were exposed
for 24 months to 50 ppm concns of 1,2-dichloroethane in
an inhalation study while at the same time being exposed to 0.05% disulfiram in
the diet &/or 5% ethanol in the drinking water. A high incidence of
intrahepatic bile duct cholangioma were reported in both sexes receiving 1,2-dichloroethane
& disulfiram, 18% incidence among males & 34% among females. Male
rats also registered 12% incidence of hepatocellular adenomas, 22% incidence for
interstitial cell tumors in the testes, 20% subcutis fibroma, & 25% mammary
adenocarcinomas in females. The expected rates for these disorders would have
been 0, 4, 4, & 8%, respectively. A slight increase in neoplastic nodules
occurred in males receiving 1,2-dichloroethane &
ethanol, 8% versus 0% expected. The DNA binding by 1,2-dichloroethane
was not altered by disulfiram treatment, & the metab of 1,2-dichloroethane
was qualitatively the same as in corresponding controls. However, the
combined treatment of 1,2-dichloroethane &
disulfiram did reduce the rate of elimination of 1,2-dichloroethane,
& sustained the blood concn levels of unchanged 1,2-dichloroethane,
which may be related to the increased carcinogenic effect of the
combination.
The in vitro metabolism of 1,2-dichloroethane
by liver homogenates of rats admin ethanol increased with the dose of
ethanol up to 4 g/kg bw, but declined sharply at 5 g/kg bw.
High doses (1000-2000 mg/kg bw) of several chemicals,
including methionine, p-aminobenzoic acid, sulfanilamide & aniline, admin
orally to mice were protective against the lethal effects caused by inhalation
of 1600 mg/cu m (400 ppm) 1,2-dichloroethane.
The acute & subacute toxicity of dichloroethane increased
when it was administered under conditions of high temperature ... .
Induction of hepatic cytochrome P-450 enzymes by phenobarbital
and/or Aroclor 1254 incr the rate of MFO /mixed function oxidation/ metabolism
of 1,2-dichloroethane in vitro ... . Alterations in
metabolism could potentially produce profound effects on toxicity. Enhanced
enzymatic metabolism of 1,2-dichloroethane also occurs
after treatment with ethanol in vitro ... . Ethanol is an inducer of cytochrome
P-450 2E1, the primary MFO enzyme involved in 1,2-dichloroethane
metabolism ... .
Concurrent admin of 0.15% disulfiram in the diet and inhaled 1,2-dichloroethane
(10, 153-304, 455 ppm) in animals markedly incr hepatotoxicity much more
than would occur with exposure to 1,2-dichloroethane alone
... . Similarly, after chronic cotreatment with 50 ppm of 1,2-dichloroethane
by inhalation and 0.05% disulfiram in the diet for 2 yr, a series of
neoplastic lesions were produced in rats that were not produced by 1,2-dichloroethane
(or disulfiram) alone ... . The lesions included intrahepatic bile duct
cholangiomas, sc fibromas, hepatic neoplastic nodules, interstitial cell tumors
in the testes, and mammary adenocarcinomas.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
1,2-Dichloroethane's production and
use as a chemical intermediate, in soaps, lead scavenger, solvent, and former
use as a fumigant may result in its release to the environment through various
waste streams. If released to air, a vapor pressure of 78.9 mm Hg at 25 deg C
indicates 1,2-dichloroethane will exist solely as a
vapor in the ambient atmosphere. Vapor-phase 1,2-dichloroethane
will be degraded in the atmosphere by reaction with photochemically-produced
hydroxyl radicals; the half-life for this reaction in air is estimated to be 63
days. Indirect evidence for photooxidation of 1,2-dichloroethane
comes from the observation that monitoring levels are highest during the
night and early morning. If released to soil, 1,2-dichloroethane
is expected to have very high mobility based upon a Koc of 33.
Volatilization from moist soil surfaces is expected to be an important fate
process based upon a Henry's Law constant of 1.18X10-3 atm-cu m/mole. 1,2-Dichloroethane
may volatilize from dry soil surfaces based upon its vapor pressure.
Biodegradation in soil or water is not expected to be an important environmental
fate process based upon a variety of biodegradation test data. If released into
water, 1,2-dichloroethane is not expected to adsorb to
suspended solids and sediment based upon the Koc. Volatilization from water
surfaces is expected to be an important fate process based upon this compound's
Henry's Law constant. Estimated volatilization half-lives for a model river and
model lake are 4 hrs and 4 days, respectively. A BCF of 2 suggests
bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be
an important environmental fate process since this compound lacks functional
groups that hydrolyze under environmental conditions. Occupational exposure to 1,2-dichloroethane
may occur through inhalation and dermal contact with this compound at
workplaces where 1,2-dichloroethane is produced or
used. Monitoring data indicate that the general population may be exposed to 1,2-dichloroethane
via inhalation of ambient air, ingestion of food and drinking water, and
dermal contact with this compound and consumer products containing 1,2-dichloroethane.
(SRC)
Probable Routes of Human Exposure:
... WORKERS PRIMARILY EXPOSED TO 1,2-DICHLOROETHANE
WERE THOSE IN HOSPITALS, BLAST FURNACES, STEEL MILLS AND AIR
TRANSPORTATION INDUSTRIES.
NIOSH (NOES Survey 1981-1983) has statistically estimated that
83,246 workers (33,361 of these are female) are potentially exposed to 1,2-dichloroethane
in the US(1). Occupational exposure to 1,2-dichloroethane
may occur through inhalation and dermal contact with this compound at
workplaces where 1,2-dichloroethane is produced or
used(SRC). Monitoring data indicate that the general population may be exposed
to 1,2-dichloroethane via inhalation of ambient air,
ingestion of food and drinking water, and dermal contact with this compound and
consumer products containing 1,2-dichloroethane(SRC). 5
of 1043 household products were found to contain 1,2-dichlroethane, a 0.5%
occurrence(2). These include automotive products (0.6% frequency, 0.1% w/w avg
concn), oils, greases and lubricants (2.6% frequency, 0.1% w/w avg concn), and
miscellaneous products (3.2% frequency, 0% w/w avg concn)(2). 12.5 million
people are estimated to be exposed to avg annual concn of 0.009-9 ppb near
production facilities(2). The exposure estimate from filling tank with gasoline
is 0.1 ug/day (time-weighted avg)(2).
Body Burden:
1,2-Dichloroethane was detected in
human breath of residents from Old Love Canal, Niagara Falls, NY at a concn of
0-54 parts/trillion, 4 of 9 samples pos and in urine at a concn of 0-140
parts/trillion, 3 of 9 samples pos(1). It was detected in mothers' milk of women
had occupational exposure of up to 14 ppm at a concn of 5.4-6.4 ppm immediately
after exposure(2).
Natural Pollution Sources:
1,2-Dichloroethane is not known to
occur as a natural product(1).
Artificial Pollution Sources:
1,2-Dichloroethane's production and
use as a chemical intermediate, in soaps, lead scavenger, solvent(1), and former
use as a fumigant(1,2) may result in its release to the environment through
various waste streams(SRC). Chlorination of water does not appear to contribute
to 1,2-dichloroethane in drinking water(3).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification scheme(1), a Koc
value of 33(2) indicates that 1,2-dichloroethane is
expected to have very high mobility in soil(SRC). Volatilization of 1,2-dichloroethane
from moist soil surfaces is expected to be an important fate process(SRC)
given a estimated Henry's Law constant of 1.18X10-3 atm-cu m/mole(3). The
potential for volatilization of 1,2-dichloroethane from
dry soil surfaces may exist(SRC) based upon a vapor pressure of 78.9 mm Hg(4).
Biodegradation is not expected to be an important environmental fate process in
soil as indicated by a variety of biodegradation tests(SRC); the percent BOD
produced in aerobic systems using sewage seed or activated sludge in 5-10 days
was 0-7%(5-7).
AQUATIC FATE: Based on a classification scheme(1), Koc value
of 33(2) indicates that 1,2-dichloroethane is not
expected to adsorb to suspended solids and sediment(SRC). Volatilization from
water surfaces is expected(3) based upon a Henry's Law constant of 1.18X10-3 atm-cu
m/mole(4). Using this Henry's Law constant and an estimation method(3),
volatilization half-lives for a model river and model lake are 4 hrs and 4 days,
respectively(SRC). Hydrolysis is not expected to be an important environmental
fate process since 1,2-dichloroethane lacks functional
groups that hydrolyze under environmental conditions(5). According to a
classification scheme(6), a BCF of 2(7), suggests bioconcentration in aquatic
organisms is low(SRC). Biodegradation is not expected to be an important
environmental fate process in water(SRC). The percent BOD produced in aerobic
systems using sewage seed or activated sludge in 5-10 days was 0-7%(8-10).
ATMOSPHERIC FATE: According to a model of gas/particle
partitioning of semivolatile organic compounds in the atmosphere(1), 1,2-dichloroethane,
which has a vapor pressure of 78.9 mm Hg at 25 deg C(2), is expected to
exist solely as a vapor in the ambient atmosphere. Vapor-phase 1,2-dichloroethane
is degraded in the atmosphere by reaction with photochemically-produced
hydroxyl radicals(SRC); the half-life for this reaction in air is estimated to
be 63 days(SRC), calculated from its rate constant of 2.48X10-13 cu
cm/molecule-sec at 25 deg C(3). Indirect evidence for photooxidation of 1,2-dichloroethane
comes from the observation that monitoring levels are highest during the
night and early morning(4).
Environmental Biodegradation:
AEROBIC: Biodegradability tests with 1,2-dichloroethane
resulted in little or no biodegradation in aerobic systems using sewage
seed or activated sludge(1-5). The one river die-away test reported no
degradation(1). The percent BOD produced in 5-10 days was 0-7%(2-4). Another
investigator reported slow to moderate biodegradation activity(5). In a
bioreactor study using microbial consortia enriched from subsurface sediments
contaminated with chlororinated hydrocarbons, a mixed-organic waste containing
21 ug/l of 1,2-dichloroethane was degraded to <5 ug/l
after a 21 day run(6).
ANAEROBIC: No degradation of 1,2-dichloroethane
occurred in an acclimated anaerobic system after 4 months incubation(1).
The attenuation rate constant in a groundwater plume for 1,2-dichloroethane
was 0.27/yr based on a study at the West KL Avenue Landfill, Kalamazoo,
MI via the use of vertical profile sampling of monitoring wells on the site(2).
Environmental Abiotic Degradation:
The rate constant for the vapor-phase reaction of 1,2-dichloroethane
with photochemically-produced hydroxyl radicals has been estimated as
2.48X10-13 cu cm/molecule-sec at 25 deg C(1). This corresponds to an atmospheric
half-life of about 63 days at an atmospheric concentration of 5X10+5 hydroxyl
radicals per cu cm(1). The direct photolysis of 1,2-dichlorethane is not an
important environmental fate process(2). Indirect evidence for photooxidation of
1,2-dichloroethane comes from the observation that
monitoring levels are highest during the night and early morning(5). The
products of photooxidation are CO2 and HCl(4). The tropospheric lifetime in the
Northern Hemisphere has been estimated at 0.32 yrs(3). A hydrolysis half-life of
50,000 yrs was approximated for 1,2-dichloroethane(3).
However, in a test designed to simulate oxygen-deficient natural waters,
reaction of 1,2-dichloroethane with water and hydrogen
sulfide ion has demonstrated that primary chloroalkanes are susceptible to
abiotic dehalogenation by both agents under conditions that are environmentally
relevant, i.e. 15 deg C , pH 7, 10-6 to 10-3 total sulfide(6). Although firm
experimental data are lacking, the photooxidation of 1,2-dichloroethane
in water is expected to be slow(4).
Environmental Bioconcentration:
A BCF of 2 was measured for 1,2-dichloroethane
in bluegill sunfish, Lepomis macrochirus(1). According to a
classification scheme(2), this BCF suggests bioconcentration in aquatic
organisms is low(SRC).
Soil Adsorption/Mobility:
The Koc for 1,2-dichloroethane is
33(1). According to a classification scheme(2), this estimated Koc value
suggests that 1,2-dichloroethane is expected to have
very high mobility in soil(SRC). 1,2-Dichloroethane rapidly
percolates through sandy soil(3).
Volatilization from Water/Soil:
The Henry's Law constant for 1,2-dichloroethane
is 1.18X10-3 atm-cu m/mole(1). This Henry's Law constant indicates that 1,2-dichloroethane
is expected to volatilize from water surfaces(2). Based on this Henry's
Law constant, the volatilization half-life from a model river (1 m deep, flowing
1 m/sec, wind velocity of 3 m/sec)(2) is estimated as 4 hours(SRC). The
volatilization half-life from a model lake (1 m deep, flowing 0.05 m/sec, wind
velocity of 0.5 m/sec)(2) is estimated as 4 days(SRC). 1,2-Dichloroethane's
Henry's Law constant indicates that volatilization from moist soil
surfaces may occur(SRC). The potential for volatilization of 1,2-dichloroethane
from dry soil surfaces may exist(SRC) based upon a vapor pressure of 78.9
mm Hg(3).
Environmental Water Concentrations:
GROUNDWATER: 1,2-Dichlorethane was detected in raw groundwater
samples from 13 US cities at a concn of 0.2 ppb, 7.7% pos(1). In a US State
groundwater survey, 2 states reported concns of 400 ppb max, and 7% were
positive(2). Well water samples from the Aerojet General Rocket Plant,
Sacramento contained up to 52 ppm 1,2-dichloroethane(3).
1,2-Dichloroethane was detected at 0.14 uM, 0.57 uM,
and 43 uM and 7.0 uM in slightly, moderately, and heavily contaminated
monitoring wells, respectively, from the DuPont Necco Park Landfill in Niagara
Falls, NY(4).
DRINKING WATER: In a survey of 133 US cities, 1,2-dichloroethane
was detected in finished surface water at a concn of 0.8-4.8 ppb, 1.8 ppb
median, 4.5% pos(1) and in samples of finished groundwater from 25 US cities at
a concn of 0.2 ppb avg, 4.0% pos(1). According to the National Organic
Monitoring Survey (1976-77), 3 of 218 samples were positive, limits of detection
<0.2 ppb(2). The compound was detected in 7 wells in the Central Sands area
of Wisconsin, 2 of which exceeded the recommended health advisory of 7 ppb
(detection limit= 0.1-3.0 ppb)(3). Average annual concns of 1,2-dichloroethane
in California public drinking water sources are as follows: (1984) 1.55
ug/l; (1985) 4.40 ug/l; (1986) 1.51 ug/l; (1987) 1.68 ug/l; (1988) 2.73 ug/l;
(1989) 3.43 ug/l; (1990) 3.32 ug/l; (1991) 3.65 ug/l; (1992) 3.86 ug/l(4).
SURFACE WATER: 1,2-Dichloroethane was
reported in US samples as follows: 6 river basins, 1-90 ppb, 53 of 204 sites
pos, only 1 site above 15 ppb(1); Ohio R basin (1977-1978) 0.1-29 ppb, 39 of 243
samples pos(2); Ohio R basin (1980-1981, 4972 samples) 7% pos, 44 samples 1-10
ppb(3); 105 USA cities - raw drinking water 1-4 ppb, 0.55 ppb median, 9.5%
pos(4); 80 USA municipal water systems - raw water 0-0.3 ppb, 14% pos(5); Lake
Erie - 2 sites, 4 ppb, 1 site pos(6).
SEAWATER: In samples from the Gulf of Mexico, 1,2-dichloroethane
was reported at 0-210 parts/trillion in areas with anthropogenic
influence and not detected in unpolluted areas(1). Marine sample concns from
various estuaries were as follows (detection limit of 25 ug/l): Humber, UK,
1992: <25 ug/l; Tees, UK, 1992 720-4,020 ug/l; Tyne, UK 1992: <25 ug/l;
Wear, UK, 1992: <25 ug/l; Tweed, UK, 1992: <25 ug/l; Scheldt,
Netherlands/Belgium, 1993: 48.0 ug/l; Brazos River, US, 1981-82: 9-51 ug/l(2).
Effluent Concentrations:
Industries whose wastewater may exceed a mean 1,2-dichloroethane
concn of 1000 ppb include: photographic equipment/supplies,
pharmaceutical mfg and organic chemicals/plastics mfg; max concn in wastewater
was 14 ppm (pharmaceutical mfg)(1). 1,2-Dichloroethane was
detected in one of 4 monitoring well headspace gases at a municipal solid waste
disposal facility at a concn of 0.09 ng/cu m; not detected in the other three
monitoring wells, and absent from groundwater samples(2). The compound was
detected, not quantified, in the flue gas of a municipal waste incinerator in
Karlsruhe, Germany(3). 1,2-Dichloroethane is one of the
priority pollutants released to Newark Bay, NJ(4). The global emission rate to
the Northern Hemisphere has been estimated to be 400 - 500 ktons per yr and the
mean concn from 1982 to 1985 was 12 parts/trillion volume; the mean concn in the
Southern Hemisphere in 1985 was <1 parts/trillion volume(5).
Sediment/Soil Concentrations:
SOIL: According to the STORET database, 1,2-dichloroethane
was not detected in sediment from lower Mississippi (1 sample) and
Western Gulf (14 samples). In 20 sediment samples from the Pacific Northwest, 5
ug/g avg and max concns were reported(1).
SEDIMENT: According to the STORET database, 20 sediment
samples from the Pacific Northwest contained 5 ug/g avg and max concns of 1,2-dichloroethane(1).
Atmospheric Concentrations:
Atmospheric industrial concn determined: rubber cementing
85-110 ppm (max 200), leather finishing 125 ppm (max 210), drum filling 35 ppm
(max 45), metal cleaning 180 ppm (max 250).
URBAN/SUBURBAN: 1,2-Dichloroethane was
detected in 1230 US samples at a concn of 120 parts/trillion avg(1); samples
from 7 US cities contained 110-1380 parts/trillion avg, 7300 parts/trillion
max(2,3). The compounds was detected in samples from 3 western USA cities at a
concn of 83-519 parts/trillion avg, 1450 parts/trillion max(4). Samples from 5
areas in NJ contained 940-1500 parts/trillion avg, with 22-44% pos, 16000
parts/trillion max(5). The estimated air concn for 360,000 Los Angeles residents
(Feb 1984) - 0.2 ug/cu m; 330,000 Los Angeles residents (May 1984) - 0.06 g/cu
m; 91,000 Contra Costa residents (June 1984) - 0.5 ug/cu m; avg of arithmetic
means of day and night 12 hr samples(7).
RURAL/REMOTE: 1,2-Dichloroethane was
not detected in 9 US samples, detection limit not specified(1).
SOURCE DOMINATED: 1,2-Dichloroethane was
detected in 436 US samples at a concn of 1,200 parts/trillion avg(1); concns as
high as 16, 38 and 45-113 ppb have been recorded at 3 production and use
sites(2).
Food Survey Values:
Market basket samplings of meat, oil and fats, tea, fruits and
vegetables contained 1,2-dichloroethane at a concn
range of 1-10 ppb, the largest amount being found in olive oil(1). It was not
detected in wheat, flour, bran, middlings, and bread(1). Concns in spice
oleoresins were 2-23 ppm, 11 of 17 spices positive(1,2). The avg concn from 549
food items surveyed was 30 ng/g in 1 of 849 findings(3).
Fish/Seafood Concentrations:
Results reported in the STORET database are as follows: fish
tissue: Lower Mississippi (2 samples) and Western Gulf (3 samples) - not
detected; Pacific Northwest (37 samples) 0.05-20 ppm, 0.7 ppm avg; Alaska (6
samples) 0.05 ppm avg and max Data in this report are listed under
dichloroethanes, however 1,2-dichloroethane is the most
commonly used isomer(1). 1,2-Dichloroethane was not
detected in marine invertebrates and fish from Liverpool Bay, England(2).
Milk Concentrations:
1,2-Dichloroethane was detected in
mothers' milk of women had occupational exposure of up to 14 ppm at a concn of
5.4-6.4 ppm immediately after exposure(1).
Environmental Standards & Regulations:
TSCA Requirements:
Section 8(a) of TSCA requires manufacturers of this chemical
substance to report preliminary assessment information concerned with
production, use, and exposure to EPA as cited in the preamble in 51 FR 41329.
CERCLA Reportable Quantities:
Persons in charge of vessels or facilities are required to
notify the National Response Center (NRC) immediately, when there is a release
of this designated hazardous substance, in an amount equal to or greater than
its reportable quantity of 100 lb or 45.4 kg. The toll free number of the NRC is
(800) 424-8802; In the Washington D.C. metropolitan area (202) 426-2675. The
rule for determining when notification is required is stated in 40 CFR 302.4
(section IV. D.3.b).
RCRA Requirements:
U077; As stipulated in 40 CFR 261.33, when ethylene
dichloride, as a commercial chemical product or manufacturing chemical
intermediate or an off-specification commercial chemical product or a
manufacturing chemical intermediate, becomes a waste, it must be managed
according to Federal and/or State hazardous waste regulations. Also defined as a
hazardous waste is any residue, contaminated soil, water, or other debris
resulting from the cleanup of a spill, into water or on dry land, of this waste.
Generators of small quantities of this waste may qualify for partial exclusion
from hazardous waste regulations (40 CFR 261.5).
D028; A solid waste containing 1,2-dichloroethane
may or may not become characterized as a hazardous waste when subjected
to the Toxicity Characteristic Leaching Procedure listed in 40 CFR 261.24, and
if so characterized, must be managed as a hazardous waste.
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. 1,2-Dichloroethane
is produced, as an intermediate or final product, by process units
covered under this subpart.
Listed as a hazardous air pollutant (HAP) generally known or
suspected to cause serious health problems. The Clean Air Act, as amended in
1990, directs EPA to set standards requiring major sources to sharply reduce
routine emissions of toxic pollutants. EPA is required to establish and phase in
specific performance based standards for all air emission sources that emit one
or more of the listed pollutants. 1,2-Dichloroethane is
included on this list.
Clean Water Act Requirements:
Ethylene dichloride is designated as
a hazardous substance under section 311(b)(2)(A) of the Federal Water Pollution
Control Act and further regulated by the Clean Water Act Amendments of 1977 and
1978. These regulations apply to discharges of this substance. This designation
includes any isomers and hydrates, as well as any solutions and mixtures
containing this substance.
Federal Drinking Water Standards:
EPA 5 ug/l
State Drinking Water Standards:
(CA) CALIFORNIA 0.5 ug/l
(FL) FLORIDA 3 ug/l
(NJ) NEW JERSEY 2 ug/l
State Drinking Water Guidelines:
(AZ) ARIZONA 0.38 ug/l
(CT) CONNECTICUT 1 ug/l
(ME) MAINE 5 ug/l
(MN) MINNESOTA 4 ug/l
FDA Requirements:
Ethylene dichloride is an indirect
food additive for use as a component of adhesives.
The food additive ethylene dichloride may
be safely used in the manufacture of animal feeds in accordance with the
following prescribed conditions: (a) It is used as a solvent in the extraction
processing of animal byproducts for use in animal feeds. (b) The maximum
quantity of the additive permitted to remain in or on the extracted byproducts
shall not exceed 300 ppm. (c) The extracted animal byproduct is added as a
source of protein to a total ration at levels consistent with good feeding
practices, but in no event exceeding 13 percent of the total ration.
Chemical/Physical Properties:
Molecular Formula:
C2-H4-Cl2
Molecular Weight:
98.96
Color/Form:
CLEAR, COLORLESS, OILY LIQUID
Clear liquid at ambient temperatures
Colorless liquid [Note: Decomposes slowly, becomes acidic
& darkens in color].
Colorless, oily liquid
Odor:
Pleasant odor
Chloroform-like odor
Sweet
Taste:
Sweet taste
Boiling Point:
83.5 deg C
Melting Point:
-35.3 deg C
Corrosivity:
Corrodes iron and other metals at elevated temperatures when
in contact with water.
Iron and zinc do not corrode when dry 1,2-dichloroethane
is used, whereas aluminum shows strong dissolution. Increased water
content leads to increased corrosion of iron and zinc; aluminum, however,
corrodes less.
Critical Temperature & Pressure:
CRITICAL TEMP: 290 DEG C; CRITICAL PRESSURE: 52.90 ATM.
Density/Specific Gravity:
1.2351 @ 20 deg C
Heat of Combustion:
12.57 kJ/g
Heat of Vaporization:
76.4 CAL/G
Octanol/Water Partition Coefficient:
log Kow = 1.48
Solubilities:
0.869 G/100 ML WATER @ 20 DEG C
Miscible with alcohol, chloroform, ether
Soluble in acetone; very soluble in ethanol; miscible in ethyl
ether.
Soluble in benzene, carbon tetrachloride, and organic
solvents.
Miscible with alcohol
Solubility in water @ 20 deg C - 0.86% wt
In water, 8,600 mg/l @ 25 deg C.
Spectral Properties:
UV absorbance (1 cm cell vs water) @ wavelength 400-300 nm=
absorbance of 0.01 ... @ wavelength 230 nm= absorbance of 1.0 /from table/.
Index of refraction: 1.4448 @ 20 deg C/D
Intense mass spectral peaks: 62 m/z (100%), 49 m/z (40%), 64
m/z (32%), 63 m/z (19%)
IR: 20 (Sadtler Research Laboratories IR Grating Collection)
NMR: 7304 (Sadtler Research Laboratories Spectral Collection)
MASS: 216 (Atlas of Mass Spectral Data, John Wiley & Sons,
New York)
Surface Tension:
32.2 dynes/cm = 0.0322 N/m at 20 deg C
Vapor Pressure:
78.9 mm Hg @ 25 deg C
Viscosity:
0.84 cP @ 20 deg C
Other Chemical/Physical Properties:
1 PPM IN AIR= 4 MG/CU M
Resistant to oxidation
LIQUID-WATER INTERFACIAL TENSION: (EST) 30 DYNES/CM @ 25 DEG
C; RATIO OF SPECIFIC HEAT OF VAPOR: 1.118
Thermal conductivity: 0.143 W/(MK) @ 20 deg C (liq)
Dielectric constant: 10.45 @ 20 deg C (liq), 1.0048 @ 120 deg
C (vapor)
Dipole moment: 1.57 debye
Coefficient of cubical expansion: 0.00116 ml/g @ 0-30 deg C
Heat of formation: 157.3 kJ/gmole (liq) 122.6 kJ/gmole (vapor)
Specific heat: 1.288 @ 20 deg C, liq; 1.066 @ 20 deg C, gas
Latent heat of fusion: 88.36 J/g
Saturation concn 350 g/cu m (20 deg C), 537 g/cu m (30 deg C).
Latent heat of sublimation= 35.4 kJ/mole @ 25 deg C.
Ionization potential= 11.04 eV.
Heat capacity at constant pressure= 135 J/mole 0 deg C @ 25
deg C, at constant volume= 121 J/mole 0 deg C (25 deg C).
Liquid interfacial tension with air 24.15 m N/m @ 20 deg C.
IN PRESENCE OF AIR, MOISTURE & LIGHT, @ ORDINARY TEMP,
DARKENS IN COLOR.
Gibbs (free) energy of formation @ 25 deg C: -19.03 kcal/mole
(liq), -17.65 kcal/mole (gas); entropy @ 25 deg C: 49.84 cal/deg/mole (liq),
73.66 cal/deg/mole (gas)
Ethylene dichloride forms azeotropes
with: 18% allyl alcohol, bp 79.9 deg C; 6% tert-amyl alcohol, bp 83 deg C; 79%
carbon tetrachloride, bp 75.6 deg C; 19.5% 1,1-dichloroethane, bp 72 deg C; 17%
ethanol, bp 70.3 deg C; 38% formic acid, bp 77.4 deg C; 6.5% isobutanol, bp 83.5
deg C; 43.5% isopropyl alcohol, bp 74.7 deg C; 19% propanol, bp 80.7 deg C; 10%
n-propyl formate 84.1, bp deg C; 18% trichloroethylene, bp 82.9 deg C; 12%
methanol, bp 61 deg C; 8.2% water, bp 70.5 deg C
Specific resistivity: 9.0x10+6 ohms/cm.
Henry's Law constant = 1.18X10-3 atm-cu m/mole @ 25 deg C
Hydroxyl radical reaction rate constant = 2.48X10-13 cu
cm/molecule-sec @ 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 confined areas (sewers,
basements, tanks). Vapor explosion hazard indoors, outdoors or in sewers. Those
substances labeled "P" may polymerize 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.
Health: May cause toxic effects if inhaled or absorbed through
skin. Inhalation or contact with material may irritate or burn skin and eyes.
Fire will produce irritating, corrosive and/or toxic gases. Vapors may cause
dizziness or suffocation. Runoff from fire control or dilution water may cause
pollution.
Public safety: Call Emergency Response Telephone Number. ...
Isolate spill or leak area immediately for at least 50 to lOO meters (160 to 330
feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out
of low areas. Ventilate closed spaces before entering.
Protective clothing: Wear positive pressure self-contained
breathing apparatus (SCBA). Structural firefighters' protective clothing will
only provide limited protection.
Evacuation: ... 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.
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. Do not use dry chemical
extinguishers to control fires involving nitromethane or nitroethane. 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
tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor
nozzles; if this is impossible, withdraw from area and let fire burn.
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.
First aid: Move victim to fresh air. Call 911 or emergency
medical service. 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. Effects of exposure (inhalation, ingestion or skin
contact) to substance may be delayed. Ensure that medical personnel are aware of
the material(s) involved, and take precautions to protect themselves.
Odor Threshold:
Although olfactory warning properties are limited by
development of tolerance, this ... liquid has an odor detectable between 6 &
40 ppm.
Of 20 subjects, 13 could detect ethylene
dichloride at 6 ppm (23.2-24.9 mg/cu m), 6 persons could detect it at 4.5
ppm (17.5 mg/cu m), and 1 person at 3 ppm (12.2 mg/cu m).
Odor is not a dependable guide for avoiding dangerous chronic
exposures to EDC. The odor may be considered pleasant until well above 180 ppm,
and may be missed below 100 ppm.
Detection in air= 2.5X10-2 mg/l (gas), chemically pure
Odor threshold low: 24 mg/cu m; high: 440 mg/cu m.
Skin, Eye and Respiratory Irritations:
Vapors are irritating.
Fire Potential:
Flammable liquid ...
Flammable liquid. A dangerous fire hazard when exposed to
heat, flame, or oxidizers.
NFPA Hazard Classification:
Health: 2. 2= Materials that, on intense or continued (but not
chronic) exposure, could cause temporary incapacitation or possible residual
injury, including those requiring the use of respiratory protective equipment
that has an independent air supply. These materials are hazardous to health, but
areas may be entered freely if personnel are provided with full-face mask
self-contained breathing apparatus that provides complete eye protection.
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 flammable limit: 6.2% by volume; Upper flammable limit:
16% by volume
Flash Point:
13 deg C, 56 deg F (closed cup)
Autoignition Temperature:
413 deg C (775 deg F)
Fire Fighting Procedures:
Do not extinguish until release can be stopped. Cool
fire-exposed containers with water staying clear of tank ends.
Wear self-contained breathing apparatus with full face-piece
operated in positive pressure mode.
If material on fire or involved in fire: Do not extinguish
fire unless flow can be stopped. Use water in flooding quantities as fog. Solid
streams of water may spread fire. Cool all affected containers with flooding
quantities of water. Apply water from as far a distance as possible. Use foam,
dry chemical, or carbon dioxide.
Use dry chemical, foam, carbon dioxide, or water spray. Water
may be ineffective. Use water spray to keep fire-exposed containers cool.
Approach fire from upwind to avoid hazardous vapors and toxic decomposition
products.
Toxic Combustion Products:
Products of combustion include noxious gases: phosgene,
hydrogen chloride, acetylene, and vinyl chloride.
Firefighting Hazards:
Vapor is heavier than air and may travel to a source of
ignition and flash back.
Explosive Limits & Potential:
lel: 6.2%, uel: 15.9%
Moderately explosive in the form of vapor when exposed to
flame.
Hazardous Reactivities & Incompatibilities:
Explosion can result when ethylene
dichloride, is mixed with liquid ammonia, dimethylaminopropylamine,
nitrogen tetroxide, metal powders, organic peroxides reducing agents, &
alkali & alkali earth metals. Mixtures with nitric acid are easily detonated
by heat, impact, or friction. Mixtures with mercaptans form thioethers &
generate heat while mixtures with nitrides generate heat & ammonia forming
toxic fumes.
In the presence of UV light, air, moisture, or heat liberates
toxic quantities of phosgene, hydrogen chloride, carbon monoxide, carbon
dioxide, acetylene, or vinyl chloride.
Incompatibilites: Strong oxidizers & caustics, chemically
active metals, such as ... magnesium powder, sodium ... .
Mixtures of /dinitrogen/ tetraoxide with ... 1,2-dichloroethane
are explosive when subjected to shock of 25 g TNT equivalent or less.
A virtually unvented aluminum tank containing a 4:1:2 mixture
of o-dichlorobenzene, 1,2-dichloroethane, and
1,2-dichloropropane exploded violently seven days after filling. This was
attributed to formation of aluminum chloride which catalyzed ... /corrosive
action/ on the aluminum tank.
Although apparently stable on contact, mixtures of potassium
(or its alloys) with range of halocarbons are shock-sensitive & may explode
with great violence on light impact. Chloroethane, dichloroethane ... are among
those investigated.
Although some mixtures of the two components /chlorine & 1,2-dichloroethane/
will burn, even that with 34% of haloalkane leads only to 2-fold pressure
increase.
Mixtures /of 1,2-dichloroethane &
nitric acid/ are easily detonated by heat, impact or friction.
Strong oxidizers & caustics; chemically-active metals such
as aluminum or magnesium powder, sodium & potassium; liquid ammonia (Note:
decomposes to vinyl chloride & HCl above 1112 deg F).
Hazardous Decomposition:
Ethylene dichloride decomposes slowly
becoming acidic and darkening in color.
AT /TEMP/ GREATER THAN 600 DEG C, DECOMPOSES TO VINYL
CHLORIDE, HYDROGEN CHLORIDE, AND ACETYLENE. /SRP: PHOSGENE IS ALSO FORMED/.
Prior History of Accidents:
1.3 million liters were spilled in a lake due to overfilling
of a river barge. One month later a large pool of concn 1,2-dichloroethane
110 m x 36 m x 0.7 m deep was lying in 10 m of water at the river bottom,
as detected by a ... sonar laser device. Dispersal was negligible with adjacent
water samples showing 1,2-dichloroethane in the ppb
range. 1.1 million liters were recovered using a suction pump for purification
and resale. Fish concn were in the range of 2-4 ppb at the time of cleanup.
A train containing hazardous chemicals derailed, and 166,090
gallons of ethylene dichloride and 58,970 gallons of
ethylene glycol spilled into ... /a Canadian/ river. Within 1 hr the site was
determined as stable, and all persons at the accident site were safe. Local
public health officials, the police, and a chemical company worked together to
establish confidence and disseminate information. The solubility of ethylene
dichloride suggested that it might present problems to the water supply.
Ethylene glycol did not pose the same intensity of concern because it was less
toxic and soluble in water. Some water systems using water directly from the
river were closed. Three days after the spill, laboratory analysis showed that
the taste and odor threshold for ethylene dichloride were
exceeded. Consequently, the river was closed. A sampling from the river after 8
weeks indicated that the criterion of a concentration of 7 micrograms per liter
was reached. No fish were killed, and spawning was not disturbed. A review of
the accident, the chemicals, and laboratory data resulted in the closing of
other water systems that were at risk from the river. Movements of the chemicals
throughout the river were calculated.
Immediately Dangerous to Life or Health:
NIOSH has recommended that 1,2-dichloroethane
be treated as a potential human carcinogen.
Protective Equipment & Clothing:
Impervious, resistant clothing, gloves, boots, overshoes, and
bib-type aprons covering boot tops. Supplied air hoods, or suits in pits or
tanks, or where heat stress is likely.
Half mask or quarter mask facepieces operated with negative
pressure below ten times the time-weighted average or full facepieces up to 50
times the time-weighted average.
Respirator selection: Upper limit devices recommended by NIOSH:
At any detectable concentration: any self-contained breathing apparatus with a
full facepiece & operated in a pressure-demand or other positive pressure
mode or any supplied-air respirator with a full facepiece & operated in
pressure-demand or other positive pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other pressure
mode; Escape: Any air-purifying full facepiece respirator (gas mask) with a
chin-style or front- or back-mounted organic vapor canister or any appropriate
escape-type self-contained breathing apparatus.
PRECAUTIONS FOR "CARCINOGENS": ... Dispensers of liq
detergent /should be available./ ... Safety pipettes should be used for all
pipetting. ... In animal laboratory, personnel should ... wear protective suits
(preferably disposable, one-piece & close-fitting at ankles & wrists),
gloves, hair covering & overshoes. ... In chemical laboratory, gloves &
gowns should always be worn ... however, gloves should not be assumed to provide
full protection. Carefully fitted masks or respirators may be necessary when
working with particulates or gases, & disposable plastic aprons might
provide addnl protection. ... Gowns ... /should be/ of distinctive color, this
is a reminder that they are not to be worn outside the laboratory. /Chemical
Carcinogens/
For ethylene dichloride breakthrough
times less (usually significantly less) than one hour reported by (normally) two
or more testers for natural rubber, neoprene, neoprene/natural rubber, nitrile,
polyethylene (PE), chlorinated polyethylene (CPE), and polyvinyl chloride,
(PVC).
For ethylene dichloride some data
(usually from immersion tests) suggesting breakthrough times greater than one
hour are not likely for nitrile rubber/polyvinyl chloride (nitrile/PVC).
For ethylene dichloride breakthrough
times greater than one hour reported by (normally) two or more testers for
polyvinyl alcohol (PVA), and viton.
Wear appropriate personal protective clothing to prevent skin
contact.
Wear appropriate eye protection to prevent eye contact.
Recommendations for respirator selection. Condition: At
concentrations above the NIOSH REL, or where there is no REL at any detectable
cocentration. 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 with a full face piece and operated
in 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
air-purifying, full-facepiece respirator (gas mask) with a chin-style, front- or
back-mounted organic vapor canister. Any appropriate escape-type, self-contained
breathing apparatus.
Eyewash fountains should be provided in areas where there is
any possbility that workers could be exposed to the substance; this is
irrespective of the recommendation involving the wearing of eye protection.
Facilities for quickly drenching the body should be provided
within the immediate work area for emergency use where there is a possibility of
exposure. [Note: It is intended that these facilities provide a sufficient
quantity or flow of water to quickly remove the substance from any body areas
likely to be exposed. The actual determination of what constitutes an adequate
quick drench facility depends on the specific circumstances. In certain
instances, a deluge shower should be readily available, whereas in others, the
availability of water from a sink or hose could be considered adequate.]
Preventive Measures:
If material 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 knock-down vapors.
Personnel protection: 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. Wear positive pressure self-contained
breathing apparatus when fighting fires involving this material.
Contact lenses should not be worn when working with this
chemical.
Warning signs should be placed on equipment, storage tanks,
containers, and entrances to areas of use.
Employees should wash promptly when skin becomes contaminated.
Immediately remove any clothing that becomes wet to avoid flammability hazard.
SRP: Contaminated protective clothing should be segregated in
such a manner so that there is no direct personal contact by personnel who
handle, dispose, or clean the clothing. Quality assurance to ascertain the
completeness of the cleaning procedures should be implemented before the
decontaminated protective clothing is returned for reuse by the workers.
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 knock-down vapors.
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.
PRECAUTIONS FOR "CARCINOGENS": Smoking, drinking,
eating, storage of food or of food & beverage containers or utensils, &
the application of cosmetics should be prohibited in any laboratory. All
personnel should remove gloves, if worn, after completion of procedures in which
carcinogens have been used. They should ... wash ... hands, preferably using
dispensers of liq detergent, & rinse ... thoroughly. Consideration should be
given to appropriate methods for cleaning the skin, depending on nature of the
contaminant. No standard procedure can be recommended, but the use of organic
solvents should be avoided. Safety pipettes should be used for all pipetting.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": In animal laboratory,
personnel should remove their outdoor clothes & wear protective suits
(preferably disposable, one-piece & close-fitting at ankles & wrists),
gloves, hair covering & overshoes. ... Clothing should be changed daily but
... discarded immediately if obvious contamination occurs ... /also,/ workers
should shower immediately. In chemical laboratory, gloves & gowns should
always be worn ... however, gloves should not be assumed to provide full
protection. Carefully fitted masks or respirators may be necessary when working
with particulates or gases, & disposable plastic aprons might provide addnl
protection. If gowns are of distinctive color, this is a reminder that they
should not be worn outside of lab. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Operations
connected with synth & purification ... should be carried out under
well-ventilated hood. Analytical procedures ... should be carried out with care
& vapors evolved during ... procedures should be removed. ... Expert advice
should be obtained before existing fume cupboards are used ... & when new
fume cupboards are installed. It is desirable that there be means for decreasing
the rate of air extraction, so that carcinogenic powders can be handled without
... powder being blown around the hood. Glove boxes should be kept under
negative air pressure. Air changes should be adequate, so that concn of vapors
of volatile carcinogens will not occur. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Vertical laminar-flow
biological safety cabinets may be used for containment of in vitro procedures
... provided that the exhaust air flow is sufficient to provide an inward air
flow at the face opening of the cabinet, & contaminated air plenums that are
under positive pressure are leak-tight. Horizontal laminar-flow hoods or safety
cabinets, where filtered air is blown across the working area towards the
operator, should never be used. ... Each cabinet or fume cupboard to be used ...
should be tested before work is begun (eg, with fume bomb) & label fixed to
it, giving date of test & avg air-flow measured. This test should be
repeated periodically & after any structural changes. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Principles that apply
to chem or biochem lab also apply to microbiological & cell-culture labs.
... Special consideration should be given to route of admin. ... Safest method
of administering volatile carcinogen is by injection of a soln. Admin by topical
application, gavage, or intratracheal instillation should be performed under
hood. If chem will be exhaled, animals should be kept under hood during this
period. Inhalation exposure requires special equipment. ... Unless specifically
required, routes of admin other than in the diet should be used. Mixing of
carcinogen in diet should be carried out in sealed mixers under fume hood, from
which the exhaust is fitted with an efficient particulate filter. Techniques for
cleaning mixer & hood should be devised before expt begun. When mixing
diets, special protective clothing &, possibly, respirators may be required.
/Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When ... admin in
diet or applied to skin, animals should be kept in cages with solid bottoms
& sides & fitted with a filter top. When volatile carcinogens are given,
filter tops should not be used. Cages which have been used to house animals that
received carcinogens should be decontaminated. Cage-cleaning facilities should
be installed in area in which carcinogens are being used, to avoid moving of ...
contaminated /cages/. It is difficult to ensure that cages are decontaminated,
& monitoring methods are necessary. Situations may exist in which the use of
disposable cages should be recommended, depending on type & amt of
carcinogen & efficiency with which it can be removed. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": To eliminate risk
that ... contamination in lab could build up during conduct of expt, periodic
checks should be carried out on lab atmospheres, surfaces, such as walls, floors
& benches, & ... interior of fume hoods & airducts. As well as
regular monitoring, check must be carried out after cleaning-up of spillage.
Sensitive methods are required when testing lab atmospheres. ... Methods ...
should ... where possible, be simple & sensitive. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Rooms in which
obvious contamination has occurred, such as spillage, should be decontaminated
by lab personnel engaged in expt. Design of expt should ... avoid contamination
of permanent equipment. ... Procedures should ensure that maintenance workers
are not exposed to carcinogens. ... Particular care should be taken to avoid
contamination of drains or ventilation ducts. In cleaning labs, procedures
should be used which do not produce aerosols or dispersal of dust, ie, wet mop
or vacuum cleaner equipped with high-efficiency particulate filter on exhaust,
which are avail commercially, should be used. Sweeping, brushing & use of
dry dusters or mops should be prohibited. Grossly contaminated cleaning
materials should not be re-used ... If gowns or towels are contaminated, they
should not be sent to laundry, but ... decontaminated or burnt, to avoid any
hazard to laundry personnel. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Doors leading into
areas where carcinogens are used ... should be marked distinctively with
appropriate labels. Access ... limited to persons involved in expt. ... A
prominently displayed notice should give the name of the Scientific Investigator
or other person who can advise in an emergency & who can inform others (such
as firemen) on the handling of carcinogenic substances. /Chemical Carcinogens/
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.
Stability/Shelf Life:
STABLE IN PRESENCE OF ALKALI, ACIDS.
STABLE AT ORDINARY TEMP WHEN DRY; IN PRESENCE OF AIR, MOISTURE
& LIGHT, @ ORDINARY TEMP, DARKENS IN COLOR.
It is stable, resistant to oxidation, and noncorrosive.
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.
PRECAUTIONS FOR "CARCINOGENS": Procurement ... of
unduly large amt ... should be avoided. To avoid spilling, carcinogens should be
transported in securely sealed glass bottles or ampoules, which should
themselves be placed inside strong screw-cap or snap-top container that will not
open when dropped & will resist attack from the carcinogen. Both bottle
& the outside container should be appropriately labelled. ... National post
offices, railway companies, road haulage companies & airlines have
regulations governing transport of hazardous materials. These authorities should
be consulted before ... material is shipped. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": When no regulations
exist, the following procedure must be adopted. The carcinogen should be
enclosed in a securely sealed, watertight container (primary container), which
should be enclosed in a second, unbreakable, leakproof container that will
withstand chem attack from the carcinogen (secondary container). The space
between primary & secondary container should be filled with absorbent
material, which would withstand chem attack from the carcinogen & is
sufficient to absorb the entire contents of the primary container in the event
of breakage or leakage. Each secondary container should then be enclosed in a
strong outer box. The space between the secondary container & the outer box
should be filled with an appropriate quantity of shock-absorbent material.
Sender should use fastest & most secure form of transport & notify
recipient of its departure. If parcel is not received when expected, carrier
should be informed so that immediate effort can be made to find it. Traffic
schedules should be consulted to avoid ... arrival on weekend or holiday ... .
/Chemical Carcinogens/
Storage Conditions:
Store in a clean, cool, well ventilated area away from heat,
sparks, or flames. Outside or detached storage is preferred. Small quantities
can be stored in brown bottles or opaque containers due to solvent's light
sensitivity. Ground and bond metal containers for liquid transfers to prevent
static sparks.
Do not ship or store with food, feeds, drugs, clothing.
PRECAUTIONS FOR "CARCINOGENS": Storage site should
be as close as practicable to lab in which carcinogens are to be used, so that
only small quantities required for ... expt need to be carried. Carcinogens
should be kept in only one section of cupboard, an explosion-proof refrigerator
or freezer (depending on chemicophysical properties ...) that bears appropriate
label. An inventory ... should be kept, showing quantity of carcinogen &
date it was acquired ... Facilities for dispensing ... should be contiguous to
storage area. /Chemical Carcinogens/
Store in a cool, dry well ventilated location. Separate from
oxidizing materials, aluminum, ammonia.
Cleanup Methods:
Environmental considerations: land spill: Dig a pit, pond,
lagoon, holding area to contain liquid or solid material. /SRP: If time permits,
pits, ponds, lagoons, soak holes, or holding areas should be sealed with an
impermeable flexible membrane liner./ Dike surface flow using soil, sand bags,
foamed polyurethane, or foamed concrete. Absorb bulk liquid with fly ash, cement
powder, or commercial sorbents. Apply "universal" gelling agent to
immobilize spill. Apply appropriate foam to diminish vapor and fire hazard.
Environmental considerations: water spill: Use natural deep
water pockets, excavated lagoons, or sand bag. Barriers to trap material at
bottom. If dissolved, in region of 10 ppm or greater concentration, apply
activated carbon at ten times the spilled amount. Remove trapped material with
suction hoses. Use mechanical dredges or lifts to remove immobilized masses of
pollutants and precipitates.
In/on soil: Construct barriers to contain spill. Remove with
pump on vacuum equip. Absorb residue on sorbent material and shovel into covered
metal containers. In/on water: Contain by damming or water diversion. Dredge or
vacuum pump to remove contaminant, liquids, and bottom sediment. In/on air:
Knock down and disperse vapor with water spray.
Steaming followed by washing with water for purging tanks.
Hycar, an absorbent material, may be used for vapor
suppression and containment.
After containment, a universal gelling agent may be used to
solidify trapped mass. If solubilized, activated carbon (10%) may be applied.
Immobilized masses can be removed using dredges or lift.
PRECAUTIONS FOR "CARCINOGENS": A high-efficiency
particulate arrestor (HEPA) or charcoal filters can be used to minimize amt of
carcinogen in exhausted air ventilated safety cabinets, lab hoods, glove boxes
or animal rooms ... Filter housing that is designed so that used filters can be
transferred into plastic bag without contaminating maintenance staff is avail
commercially. Filters should be placed in plastic bags immediately after removal
... The plastic bag should be sealed immediately ... The sealed bag should be
labelled properly ... Waste liquids ... should be placed or collected in proper
containers for disposal. The lid should be secured & the bottles properly
labelled. Once filled, bottles should be placed in plastic bag, so that outer
surface ... is not contaminated ... The plastic bag should also be sealed &
labelled. ... Broken glassware ... should be decontaminated by solvent
extraction, by chemical destruction, or in specially designed incinerators.
/Chemical Carcinogens/
Biological degradation of 1,2-dichloroethane
under groundwater conditions.
Eliminate all ignition sources. Use appropriate foam to
blanket release and suppress vapors. Absorb in noncombustible material for
proper disposal.
Environmental considerations: air spill: Apply water spray or
mist to knock down vapors. Combustion products include corrosive or toxic
vapors.
Disposal Methods:
Generators of waste (equal to or greater than 100 kg/mo)
containing this contaminant, EPA hazardous waste number U077, must conform with
USEPA regulations in storage, transportation, treatment and disposal of waste.
Waste must never be discharged into sewers or surface waters.
Contaminated porous surfaces (sand, vemiculite, etc) should be disposed of at a
waste management facility. Recovered liquids may be reprocessed, incinerated, or
treated at a waste management facility.
Potential candidate for liquid injection incineration, with a
temp range of 650 to 1,600 deg C and a residence time of 0.1 to 2 seconds. Also
a potential candidate for rotary kiln incineration, with a temp range of 820 to
1,600 deg C and a residence time of seconds. Also a potential candidate for
fluidized bed incineration, with a temp range of 450 to 980 deg C and a
residence time of seconds.
This compound should be susceptible to removal from waste
water by air stripping.
Concentrated wastes, such as distillation residues, spent
catalysts & complex sludges, are disposed of in special waste incinerators
since phosgene is liberated during burning of 1,2-dichloroethane.
Solvent wastes from small-scale users are collected & regenerated by
commercial reprocessing businesses. Aqueous wastes which contain dichloroethane
(process effluents) are aerated until the volatile chlorohydrocarbon is
evaporated. Special attention has to be given to the emission limits.
Recommendable method: Incineration. Peer-review: Dilute with kerosene or fuel
oil due to high chlorine content. (Peer-review conclusions of an IRPTC expert
consultation (May 1985))
PRECAUTIONS FOR "CARCINOGENS": There is no universal
method of disposal that has been proved satisfactory for all carcinogenic
compounds & specific methods of chem destruction ... published have not been
tested on all kinds of carcinogen-containing waste. ... Summary of avail methods
& recommendations ... /given/ must be treated as guide only. /Chemical
Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Incineration may
be only feasible method for disposal of contaminated laboratory waste from
biological expt. However, not all incinerators are suitable for this purpose.
The most efficient type ... is probably the gas-fired type, in which a
first-stage combustion with a less than stoichiometric air:fuel ratio is
followed by a second stage with excess air. Some ... are designed to accept ...
aqueous & organic-solvent solutions, otherwise it is necessary ... to absorb
soln onto suitable combustible material, such as sawdust. Alternatively, chem
destruction may be used, esp when small quantities ... are to be destroyed in
laboratory. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": HEPA (high-efficiency
particulate arrestor) filters ... Can be disposed of by incineration. For spent
charcoal filters, the adsorbed material can be stripped off at high temp &
carcinogenic wastes generated by this treatment conducted to & burned in an
incinerator. ... LIQUID WASTE: ... Disposal should be carried out by
incineration at temp that ... ensure complete combustion. SOLID WASTE: Carcasses
of lab animals, cage litter & misc solid wastes ... should be disposed of by
incineration at temp high enough to ensure destruction of chem carcinogens or
their metabolites. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": ... Small quantities
of ... some carcinogens can be destroyed using chem reactions ... but no general
rules can be given. ... As a general technique ... treatment with sodium
dichromate in strong sulfuric acid can be used. The time necessary for
destruction ... is seldom known ... but 1-2 days is generally considered
sufficient when freshly prepd reagent is used. ... Carcinogens that are easily
oxidizable can be destroyed with milder oxidative agents, such as saturated soln
of potassium permanganate in acetone, which appears to be a suitable agent for
destruction of hydrazines or of compounds containing isolated carbon-carbon
double bonds. Concn or 50% aqueous sodium hypochlorite can also be used as an
oxidizing agent. /Chemical Carcinogens/
PRECAUTIONS FOR "CARCINOGENS": Carcinogens that are
alkylating, arylating or acylating agents per se can be destroyed by reaction
with appropriate nucleophiles, such as water, hydroxyl ions, ammonia, thiols
& thiosulfate. The reactivity of various alkylating agents varies greatly
... & is also influenced by sol of agent in the reaction medium. To
facilitate the complete reaction, it is suggested that the agents be dissolved
in ethanol or similar solvents. ... No method should be applied ... until it has
been thoroughly tested for its effectiveness & safety on material to be
inactivated. For example, in case of destruction of alkylating agents, it is
possible to detect residual compounds by reaction with
4(4-nitrobenzyl)-pyridine. /Chemical Carcinogens/
The following wastewater treatment technologies have been
investigated for 1,2-dichlorothane: Concentration process: Biological treatment.
The following wastewater treatment technologies have been
investigated for 1,2-dichloroethane: Concentration
process: Activated carbon.
The following wastewater treatment technologies have been
investigated for 1,2-dichloroethane: Concentration
process: Resin adsorption.
The following wastewater treatment technologies have been
investigated for 1,2-dichloroethane: Concentration
process: Stripping.
The following wastewater treatment technologies have been
investigated for 1,2-dichloroethane: Concentration
process: Solvent extraction.
Environment Canada's Wastewater Technology Center operated a
pilot plant at a landfill site to treat groundwater contaminated with volatile
organic chemicals during the summer of 1986. The treatment system consisted of a
packed air stripping column to treat the wastewater and two sequential granular
activated carbon adsorbers to treat the off-gases. Among volatile organic
chemicals in the wastewater were 1,1-dichloroethane, 1,2-dichloroethane,
chloroform, 1,1-dichloroethylene, 1,1,1-trichloroethane, benzene,
toluene, and trichloroethylene. Removal efficiencies varied from 27 to 99.9%.
Optimal conditions, resulting in 94% removal of all volatile organic chemicals,
were met with a 70:1 air-to-water ratio, a liquid flow rate of 4 l/min, and 1.3
cm Intalox saddles. Concentration of all compounds were below the lower
detection limit of 2 ug/l in the effluent of the second granular activated
carbon adsorber.
The adsorption capacities and rates of seven principal
chlorinated organic compounds for six commercial GACs were investigated. All the
adsorption isotherms were expressed by the Freundlich equation and the isotherms
for the chloroethylenes such as trans-1,2-dichloroethylene, trichloroethylene
and tetrachloroethylene could be shown by the modified Freundlich equation Q =
k' (C/Cs)ln for each GAC. The magnitude of adsorption of the chlorinated organic
compounds was in the order of: tetrachloroethylene > trichloroethylene >
trans-1 2-dichloroethylene > l,l-dichloroethane > carbon tetrachloride
> l,l,l-trichloroethane > chloroform. The value of k for a certain GAC
could be predicted from the quantity of pores smaller than 2 mm in diameter. The
adsorbed amounts were decreased by 10-20% when humic substances coexisted. The
working periods of a fixed bed adsorber before regeneration were predicted by
calculating breakthrough curves of various influent concentrations of
trichloroethylene and tetrachloroethylene at the space velocities of 5 or 10 hr
-l and it was certified that the adsorption method by GAC was feasible for
removing these compounds from water.
Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-2 8-hr Time Weighted Avg:
50 ppm.
Permissible Exposure Limit: Table Z-2 Acceptable Ceiling
Concentration: 100 ppm.
Permissible Exposure Limit: Table Z-2 Acceptable maximum peak
above the acceptable ceiling concentration for an 8-hour shift. Concentration:
200 ppm. Maximum Duration: 5 minutes in any 3 hours.
Threshold Limit Values:
8 hr Time Weighted Avg (TWA) 10 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:
NIOSH recommends that ethylene dichloride be
regulated as a potential human carcinogen.
NIOSH usually recommends that occupational exposures to
carcinogens be limited to the lowest feasible concn.
Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 1 ppm (4
mg/cu m).
Recommended Exposure Limit: 15 Min Short-Term Exposure Limit:
2 ppm (8 mg/cu m).
Immediately Dangerous to Life or Health:
NIOSH has recommended that 1,2-dichloroethane
be treated as a potential human carcinogen.
Manufacturing/Use Information:
Major Uses:
For 1,2-Dichloroethane (USEPA/OPP
Pesticide Code: 042003) there are 0 labels match. /SRP: Not registered for
current use in the U.S., but approved pesticide uses may change periodically and
so federal, state and local authorities must be consulted for currently approved
uses./
Solvent for fats, oils, waxes, gums, resins, and particularly
for rubber; manuf acetyl cellulose, tobacco extract, etc.
Fumigant /Former use/
Production of vinyl chloride, trichloroethylene, vinylidene
chloride, and trichloroethane; lead scavenger in antiknock gasoline; soaps and
scouring compounds; wetting and penetrating agents; organic synthesis; ore
flotation; solvent.
FUMIGANT FOR UPHOLSTERY AND CARPETS; /FORMERLY/ REGISTERED FOR
AGRIC USE IN THE USA FOR POSTHARVEST FUMIGATION OF GRAIN AND FOR USE IN
ORCHARDS, AGRIC PREMISES AND MUSHROOM HOUSES.
In leather cleaning, rubber goods fabrication, drum filling,
and metal cleaning industries.
In degreaser compounds, rubber cement, and acrylic adhesives.
Catalyst in production of hexachlorophene.
Solvent for processing pharmaceutical products.
MANUFACTURE OF ETHYLENEDIAMINE, SUCCINONITRILE, GLYCOL ETHERS
& ESTERS.
Manufacture of ethylene glycol, diaminoethylene, polyvinyl
chloride, nylon, viscose rayon, styrene-butadiene rubber, and various plastics;
solvent for resins, asphalt, bitumen, rubber; used as pickling agent and a dry
clean agent; in photography, xerography, water softening & in production of
cosmetics.
Ingredient in cosmetics (nail lacquers) and as a food additive
as a result of its use in extracting spices such as annatto, paprika, and
turmeric.
Most commonly used in the production of vinyl chloride monomer
Starting material for chlorinated solvents such as
1,1,1-trichloroethane, vinylidene chloride, trichloroethylene, and
perchloroethylene.
MEDICATION
Other synthetic resin and rubber adhesives; pharmaceutical
preparations; rug and upholstery cleaners
Polystyrene manufacture solvents; /Styrene Butadiene Rubber/
SBR latex production solvents
Manufacturers:
Borden Chemicals and Plastics, 180 East Broad St., Columbus,
OH 43215-3799, (614) 225-4000, Operating Limited Partnership; Production site:
Geismar, LA 70734
Dow Chemical USA, 2030 Dow Center, Midland, MI 48674, (517)
832- 1150; Production sites: Freeport, TX 77541; Oyster Creek, TX 77541;
Plaquemine, LA 70765
Formosa Plastics Corp., U.S.A., 9 Peach Tree Rd., Livingston,
NJ 07039, (973) 992-2090; Production sites: Baton Rouge, LA 70821; Point
Comfort, TX 77978
Georgia Gulf Corp., 400 Perimeter Center Terr., Suite 595,
Atlanta, GA 30346, (770) 395-4500; Production sites: Lake Charles, LA 70669;
Plaquemine, LA 70765-0629
Occidental Chemical Corp., 5005 LBJ Freeway, Dallas, TX 75244,
(972) 404-3800, Chloro-Vinyls Group, Basic Chemicals Div.; Production sites:
Convent, LA 70723; Corpus Christi, TX 78400
Oxymar, P.O. Box CC, Ingelside, TX 78362-0710, (316) 776-6321;
Production site: Ingleside, TX 78359
OxyVinyls LP, 5005 LBJ Freeway, Suite 500, Dallas, TX 75244,
(972) 720-7000; Production sites: Deer Park, TX 77536; La Porte, TX
(Independence Plant) 77571
PPG Industries, Inc., One PPG Place, 36 East, Pittsburgh, PA
15727, (412) 434-3131. Chemicals Group; Production site: Lake Charles, LA 70602
Vulcan Materials Co., P.O. Box 385014, Birmingham, AL
35283-5014, (202) 298-3000. Vulcan Chemicals group, Chloralkali Business Unit;
Production site: Geismar, LA 70734
Westlake Monomers Corp., Westlake Center, 2801 Post Oak Blvd.,
Houston, TX 77056; Production site: Calvert City, KY 42029
Methods of Manufacturing:
1,2-Dichloroethane is produced by the
vapor- or liquid-phase chlorination of ethylene. Most liquid-phase processes use
ferric chloride as the catalyst. ...
Action of chlorine on ethylene, with subsequent distillation
with metallic catalyst; also by reaction of acetylene and hydrochloric acid.
Made from ethylene and chlorine; also from acetylene and HCl
... Industrially produced by chlorination of ethylene ...
using chlorine (direct chlorination) or hydrogen chloride (oxychlorination) as a
chlorinating agent
Commercial production is by the chlorination of ethylene,
either directly with chlorine or by oxychlorination using hydrogen chloride and
oxygen.
HAS ... BEEN PRODUCED AS BY-PRODUCT IN CHLOROHYDRIN PROCESS
FOR MANUFACTURE OF ETHYLENE OXIDE ... .
General Manufacturing Information:
It has been replaced as a solvent & degreaser by less
toxic compounds
Formulations/Preparations:
USEPA/OPP Pesticide Code 042003; Trade Names: ENT-1656; Borer
Sol; Brocide; Destruxol Borer-Sol; Dichloremulsion;
Dowfume; Dutch Liquid; Dutch Oil; Freon 150.
Granosan: disinfectant composed of 30% carbon tetrachloride
and 70% ethylene dichloride.
Grades: Technical, spectrophotometric.
Ethylene dichloride - carbon
tetrachloride (Dowfume 75). Principal ingredient: 1,2-Dichloroethane,
commercial formulation, 70% active ingredient; & tetrachloromethane,
commercial formulation, 30% active ingredient ... .
Consumption Patterns:
Demand: 13.9x10+9 lb (1991); 14.3X10+9 lb (1992); 16.5X10+9 lb
(1996) (forecast); includes exports of 1.45x10+9 lb (1991) but not imports
estimated at 11X10+6 lb
Vinyl chloride monomer, 88%; exports, 10%, other including
chlorinated solvents and ethyleneamines, 2%.
... 85% of total ...production used for production of vinyl
chloride, 10% used in the production of chlorinated solvents... The rest goes
into various processes mainly for the synthesis of ethylenediamines.
Demand: (1999) 15.089 billion lbs; (2000) 15.632 billion lbs;
(2004) 17.938 billion lbs
Vinyl chloride monomer (VCM), 94 percent; ethyleneamines, 3
percent; 1,1,1-trichloroethane, 1 percent; vinylidene chloride, 1 percent;
miscellaneous, including trichloroethylene and perchloroethylene, 1 percent.
U. S. Production:
(1980) 5.03X10+12 G
(1981) 9,973,553,000 lb
(1983) 11,506,143,000 lb
(1990) 13.85 billion lb
(1991) 13.72 billion lb
(1992) 15.15 billion lb
(1993) 17.95 billion lb
6,220,003 kg (1991)
13th-highest-volume chemical produced in the US (1995).
U. S. Imports:
(1985) 6.36X10+9 g
(1999) 340 million lbs; (2000) 329 million lbs
U. S. Exports:
(1985) 4.42X10+11 g
(1999) 2.597 billion lbs; (2000) 2.493 billion lbs
Laboratory Methods:
Clinical Laboratory Methods:
DETERMINATION OF 1,2-DICHLOROETHANE IN
RAT BLOOD, LIVER, LUNG, SPLEEN, BRAIN, KIDNEY & EPIDIDYMAL ADIPOSE TISSUE BY
HEAD-SPACE GAS CHROMATOGRAPHY. METHOD IS SENSITIVE TO 25 NG/ML OF BLOOD OR 50
NG/G OF TISSUE.
Analytic Laboratory Methods:
NIOSH Method 1003. Analyte: 1,2-Dichloroethane;
Technique: Gas chromatography, flame ionization detection; Desorption: 1
ml carbon disulfide; stand 30 min; Injection vol: 5 ul; Temp injection: 225 deg
C, detector: 250 deg C, column: 70 deg C; Carrier gas: Helium or nitrogen, 30
ml/min; Column: 3 m x 3 mm outer diameter stainless steel, 10% OV-101 on 100/120
mesh Chromosorb WHP; alternates are SP-2100, SP-2100 with 0.1% Carbowax 1500 or
DB-1 fused silica capillary column. Calibration: Std soln of analyte in carbon
disulfide; Range: 0.02 to 0.3 mg/sample; Estimated limit of detection: 0.01
mg/sample; Precision (std relative deviation): 0.079 overall, measurement 0.012;
Interferences: None identified. The chromatographic column or separation
conditions may be changed to circumvent interferences.
AOAC Method No. 969.29. Ethylene Dichloride and
Trichloroethylene in Spice Oleoresins. Gas Chromatographic Method. Detection
limit not stated.
AOAC Method No. 966.05. Fumigant Mixtures. Gas Chromatographic
Method. Detection limit not stated.
Method is described for the time-weight-average concentration
determination of 23 volatile components including 1,2-dichloroethane
permeation through a silicone polycarbonate membrane and absorption onto
charcoal contained within the sampling device. Analysis consists of desorption
of the volatile components with carbon disulfide and then separation and
quantification by capillary column gas chromatography. Linear relationship
exists between the amount of a volatile organic component collected and the
product of the time of exposure of the sampling device to the sampling
environment and the concentration of the component in the sampling environment,
for the ranges investigated. Temperature is the only other external factor which
has been shown to affect the rate of permeation, though the change in the
permeation constant has been shown to be approximately linear with a slope of
about 0.4.
EPA Method 502.1: Volatile Halogenated Organic Compounds in
Water by Purge-and-Trap Gas Chromatography. This method is applicable for the
determination of various halogenated volatile compounds in finished drinking
water, raw source water, or drinking water in any treatment stage. ...
Organohalides and other highly volatile organic compounds with low water
solubility are extracted (purged) from the sample matrix by bubbling an inert
gas through the aqueous sample. Purged sample components are trapped in a tube
containing suitable sorbent materials. When purging is complete, the sorbent
tube is heated and backflushed with an inert gas to desorb trapped sample
components into a gas chromatography column. The gas chromatograph is
temperature programmed to separate the method analytes which are then detected
with a halogen specific detector. Using this method, 1,2-dichloroethane
has a method detection limit of 0.002 ug/l.
AOB Method VG-001-01. Volatile Organics in Soil Gas -
Adsorbent Tube Method. Quantitation limit = 20 ng/l.
EPA Method 1624-S. Volatile Organic Compounds by Isotope
Dilution GCMS. Method detection limit = 3 mg/kg.
EPA Method 1624-W. Volatile Organic Compounds by Isotope
Dilution GCMS. Method detection limit = 10 ug/l.
EPA Method 624. Protocol for the Analysis of Purgeable Organic
Priority Pollutants in Industrial and Municipal Wastewater. Method detection
limit = 2.8 ug/l.
EPA Method 624-S. Analysis of Purgeable Organic Priority
Pollutants in Industrial and Municipal Wastewater Treatment Sludge. Method
detection limit = 2.8 ug/l.
EPA Method 601. Purgeable Halocarbons in Wastewater by Gas
Chromatography with Electrolytic Conductivity Detection. Method detection limit
= 0.030 ug/l.
EPA Method 524.1. Measurement of Purgeable Organic Compounds
in Water by Packed Column Gas Chromatography and Mass Spectrometry. Revision
3.0. Method detection limit = 0.20 ug/l.
EPA Method 524.2. Measurement of Purgeable Organic Compounds
in Water by Capillary Column Gas Chromatography/Mass Spectrometry. Revision 4.0.
Method detection limit = 0.060 ug/l.
EPA Method 502.2-ELCD. Volatile Organic Compounds in Water by
Purge and Trap Capillary Column Gas Chromatography with Photoionization and
Electrolytic Conductivity Detectors in Series. Revision 2.0. Method detection
limit = 0.030 ug/l.
OSW Method 8240B-W. Determination of Volatile Organics
Compounds by Gas Chromatography/Mass Spectrometry (GC/MS). Estimated
quantitation limit = 5.0 ug/l.
OSW Method 8010B. Determination of Halogenated Volatile
Organics by Gas Chromatography. Method detection limit = 0.002 ug/l.
AREAL Method IP-1A. Determination of Volatile Organic
Compounds (VOCs) in Indoor Air Using Stainless Steel Canisters. Detection limit
not specified.
AREAL Method IP-1B. Determination of Volatile Organic
Compounds (VOCs) in Indoor Air using Solid Absorbent Tubes. Detection limit =
3.80 ng.
AREAL Method TO-14. Determination of Volatile Organic
Compounds (VOCs) in Ambient Air using SUMMA Passivated Canister Sampling and Gas
Chromatographic Analysis. Detection limit not specified.
AREAL Method TO-1. Determination of Volatile Organic Compounds
in Ambient Air using Tenax Adsorption and Gas Chromatography/Mass Spectrometry
(GC/MS). Detection limit not specified.
AREAL Method TO-2. Determination of Volatile Organic Compounds
In Ambient Air by Carbon Molecular Sieve Adsorption and Gas Chromatography/Mass
Spectrometry (GC/MS). Detection limit not specified.
AREAL Method TO-3. Determination of Volatile Organic Compounds
in Ambient Air Using Cryogenic Preconcentration Techniques and Gas
Chromatography with Flame Ionization and Electron Capture Detectors. Detection
limit not specified.
CLP Method OHC. Organics Analysis, Multi-Media,
High-Concentration. Contract required quantitation limit = 2.500 mg/kg.
CLP Method MC_VOA-LS. Analysis of Volatile Organics in Low
Concentration Soil Samples by Gas Chromatography with a Mass Spectrometer.
Contract required quantitation limit = 10 mg/kg.
CLP Method MC_VOA-MS. Analysis of Volatile Organics in Medium
Concentration Soil Samples by Gas Chromatography with a Mass Spectrometer.
Contract required quantitation limit = 1200.0 mg/kg.
OSW Method 1311. Toxicity Characteristic Leaching Procedure.
OSW Method 8240B-S. Determination of Volatile Organic
Compounds by Gas Chromatography/Mass Spectrometry (GC/MS). Estimated
quantitation limit = 5.0 ug/kg.
OSW Method 8260A. Determination of Volatile Organic Compounds
by Gas Chromatography/Mass Spectrometry (GC/MS): Capillary Column Technique.
Method detection limit = 0.060 ug/l.
Sampling Procedures:
Ethylene dichloride was collected
/from air/ on silica gel, and extracted with isopropyl alcohol ... .
NIOSH Method 1003. Matrix: air; Sampler: Solid sorbent tube
(coconut shell charcoal, 100 mg/50 mg); Flow rate: 0.01 to 0.2 l/min; Minimun
vol: 0.5 l @ 100 ppm, Max vol: 15 l; Sample stability: Not determined; Shipment:
Routine.
Special References:
Special Reports:
Environment Canada; Tech Info for Problem Spills: Ethylene
Dichloride (Draft) (1982)
USEPA; Drinking Water Criteria Document (Draft): 1,2-Dichloroethane
(1982)
USEPA; Office of Drinking Water; Health Advisory 1,2-Dichloroethane
(Draft) (1985).
USEPA; Health and Environmental Effects Profile for
Dichloroethane (1985) ECAO-CIN-P139
DHHS/ATSDR; Toxicological Profille for 1,2-Dichloroethane
(Update) (1994) ATSDR/TP-93/06
DHHS/NTP; NTP Report on the Toxicity Studies of 1,2-Dichloroethane
(Ethylene Dichloride) in F344/N Rats, Sprague Dawley Rats, Osborne-Mendel
Rats, and B6C3F1 Mice (Drinking Water Gavage Studies) NTP TOX 4 (1991) NIH Pub
No. 91-3123
DHEW/NCI; Bioassay of 1,2-Dichloroethane for
Possible Carcinogenicity (1978) Technical Rpt Series No. 55 DHEW Pub No. (NIH)
78-1361
Health and Safety Executive; 1,2-Dichloroethane
Criteria Document for an Occupational Exposure Limit 47pp. (1993). Data
on the effects of exposure to 1,2-dichloroethane is
examined.
Commission of the European Communities; Organo-chlorine
Solvents. Health Risks Workers. Pub No. EUR 10531 (1986). A review of the
thealth hazards and toxicology of 1,2-dichloroethane.
WHO; Environmental Health Criteria 62 1,2-Dichloroethylene
(1987)
U.S. Department of Health & Human Services/National
Toxicology Program; Tenth Report on Carcinogens. National Institutes of
Environmental Health Sciences. The Report on Carcinogens is an informational
scientific and public health document that identifies and discusses substances
(including agents, mixtures, or exposure circumstances) that may pose a
carcinogenic hazard to human health. 1,2-Dichloroethane (107-06-2)
was first listed in the Second Annual Report on Carcinogens (1981) as reasonably
anticipated to be a human carcinogen.
Synonyms and Identifiers:
Related HSDB Records:
2521
[CHLOROACETALDEHYDE] (Metabolite)
426
[2-CHLOROETHANOL] (Metabolite)
1100
[OXALIC ACID] (Metabolite)
6877
[DICHLOROETHANE] (Mixture)
Synonyms:
AETHYLENCHLORID (GERMAN)
**PEER REVIEWED**
1,2-BICHLOROETHANE
**PEER REVIEWED**
BICHLORURE D'ETHYLENE (FRENCH)
**PEER REVIEWED**
BORER SOL
**PEER REVIEWED**
BROCIDE
**PEER REVIEWED**
CHLORURE D'ETHYLENE (FRENCH)
**PEER REVIEWED**
CLORURO DI ETHENE (ITALIAN)
**PEER REVIEWED**
1,2-DCE
**PEER REVIEWED**
DESTRUXOL BORER-SOL
**PEER REVIEWED**
1,2-DICHLOORETHAAN (DUTCH)
**PEER REVIEWED**
1,2-DICHLOR-AETHAN (GERMAN)
**PEER REVIEWED**
DICHLOREMULSION
**PEER REVIEWED**
1,2-DICHLORETHANE
**PEER REVIEWED**
DICHLOR-MULSION
**PEER REVIEWED**
ALPHA,BETA-DICHLOROETHANE
**PEER REVIEWED**
beta-Dichloroethane
**PEER REVIEWED**
SYM-DICHLOROETHANE
**PEER REVIEWED**
1,2-DICLOROETANO (ITALIAN)
**PEER REVIEWED**
DUTCH LIQUID
**PEER REVIEWED**
DUTCH OIL
**PEER REVIEWED**
EDC
**PEER REVIEWED**
ENT 1,656
**PEER REVIEWED**
Pesticide Code 042003.
**PEER REVIEWED**
ETHANE DICHLORIDE
**PEER REVIEWED**
ETHANE, 1,2-DICHLORO-
**PEER REVIEWED**
ETHYLEENDICHLORIDE (DUTCH)
**PEER REVIEWED**
ETHYLENE CHLORIDE
**PEER REVIEWED**
ETHYLENE DICHLORIDE
**PEER REVIEWED**
1,2-ETHYLENE DICHLORIDE
**PEER REVIEWED**
FREON 150
**PEER REVIEWED**
GLYCOL DICHLORIDE
**PEER REVIEWED**
NCI-C00511
**PEER REVIEWED**
RY DICHLORO-1,2-ETHANE
**PEER REVIEWED**
Formulations/Preparations:
USEPA/OPP Pesticide Code 042003; Trade Names: ENT-1656; Borer
Sol; Brocide; Destruxol Borer-Sol; Dichloremulsion;
Dowfume; Dutch Liquid; Dutch Oil; Freon 150.
Granosan: disinfectant composed of 30% carbon tetrachloride
and 70% ethylene dichloride.
Grades: Technical, spectrophotometric.
Ethylene dichloride - carbon
tetrachloride (Dowfume 75). Principal ingredient: 1,2-Dichloroethane,
commercial formulation, 70% active ingredient; & tetrachloromethane,
commercial formulation, 30% active ingredient ... .
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1184; Ethylene dichloride
IMO 3.2; Ethylene dichloride
Standard Transportation Number:
49 091 66; Ethylene dichloride
EPA Hazardous Waste Number:
U077; A toxic waste when a discarded commercial chemical
product or manufacturing chemical intermediate or an off-specification
commercial chemical product or a manufacturing chemical intermediate.
D028; A waste containing 1,2-dichloroethane may
or may not be characterized as a hazardous waste following testing by the
Toxicity Characteristic Leaching Procedure as prescribed by the Resource
Conservation and Recovery Act (RCRA) regulations.
Administrative Information:
Hazardous Substances Databank Number: 65
Last Revision Date: 20030829
Last Review Date: Reviewed by SRP on 9/15/2001
Update History:
Complete Update on 2003-08-29, 1 fields added/edited/deleted
Complete Update on 11/08/2002, 1 field added/edited/deleted.
Complete Update on 10/31/2002, 1 field added/edited/deleted.
Complete Update on 08/15/2002, 1 field added/edited/deleted.
Complete Update on 08/06/2002, 1 field added/edited/deleted.
Complete Update on 05/31/2002, 1 field added/edited/deleted.
Complete Update on 05/15/2002, 1 field added/edited/deleted.
Complete Update on 05/13/2002, 1 field added/edited/deleted.
Complete Update on 04/19/2002, 95 fields added/edited/deleted.
Field Update on 01/14/2002, 1 field added/edited/deleted.
Field Update on 08/08/2001, 1 field added/edited/deleted.
Complete Update on 01/31/2001, 2 fields added/edited/deleted.
Complete Update on 03/24/2000, 1 field added/edited/deleted.
Complete Update on 02/11/2000, 1 field added/edited/deleted.
Complete Update on 02/08/2000, 1 field added/edited/deleted.
Complete Update on 02/02/2000, 1 field added/edited/deleted.
Complete Update on 11/18/1999, 1 field added/edited/deleted.
Complete Update on 09/21/1999, 1 field added/edited/deleted.
Complete Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 07/20/1999, 6 fields added/edited/deleted.
Complete Update on 05/04/1999, 1 field added/edited/deleted.
Complete Update on 03/29/1999, 1 field added/edited/deleted.
Complete Update on 01/20/1999, 1 field added/edited/deleted.
Complete Update on 11/16/1998, 1 field added/edited/deleted.
Complete Update on 11/12/1998, 1 field added/edited/deleted.
Complete Update on 08/10/1998, 1 field added/edited/deleted.
Complete Update on 06/02/1998, 1 field added/edited/deleted.
Complete Update on 02/25/1998, 1 field added/edited/deleted.
Complete Update on 05/08/1997, 1 field added/edited/deleted.
Complete Update on 03/27/1997, 2 fields added/edited/deleted.
Complete Update on 03/11/1997, 2 fields added/edited/deleted.
Complete Update on 01/24/1997, 1 field added/edited/deleted.
Complete Update on 12/11/1996, 1 field added/edited/deleted.
Complete Update on 10/12/1996, 1 field added/edited/deleted.
Complete Update on 09/17/1996, 1 field added/edited/deleted.
Complete Update on 06/14/1996, 1 field added/edited/deleted.
Complete Update on 05/14/1996, 1 field added/edited/deleted.
Complete Update on 04/16/1996, 8 fields added/edited/deleted.
Field Update on 01/18/1996, 1 field added/edited/deleted.
Complete Update on 06/07/1995, 74 fields added/edited/deleted.
Field Update on 01/20/1995, 1 field added/edited/deleted.
Field Update on 12/19/1994, 1 field added/edited/deleted.
Field Update on 12/19/1994, 1 field added/edited/deleted.
Field Update on 11/18/1994, 1 field added/edited/deleted.
Complete Update on 07/27/1994, 1 field added/edited/deleted.
Complete Update on 06/08/1994, 1 field added/edited/deleted.
Complete Update on 05/05/1994, 1 field added/edited/deleted.
Complete Update on 03/25/1994, 1 field added/edited/deleted.
Complete Update on 02/02/1994, 3 fields added/edited/deleted.
Field Update on 09/02/1993, 1 field added/edited/deleted.
Complete Update on 04/30/1993, 1 field added/edited/deleted.
Field update on 12/10/1992, 1 field added/edited/deleted.
Complete Update on 11/09/1992, 1 field added/edited/deleted.
Complete Update on 09/03/1992, 1 field added/edited/deleted.
Complete Update on 05/29/1992, 1 field added/edited/deleted.
Complete Update on 04/27/1992, 1 field added/edited/deleted.
Complete Update on 04/01/1992, 1 field added/edited/deleted.
Complete Update on 03/19/1992, 1 field added/edited/deleted.
Complete Update on 01/23/1992, 1 field added/edited/deleted.
Complete Update on 09/26/1991, 2 fields added/edited/deleted.
Complete Update on 07/08/1991, 1 field added/edited/deleted.
Complete Update on 01/23/1991, 61 fields added/edited/deleted.
Field Update on 03/06/1990, 1 field added/edited/deleted.
Complete Update on 01/11/1990, 62 fields added/edited/deleted.
Field Update on 05/05/1989, 1 field added/edited/deleted.
Field Update on 03/01/1989, 1 field added/edited/deleted.
Complete Update on 12/09/1988, 2 fields added/edited/deleted.
Complete Update on 09/26/1988, 108 fields added/edited/deleted.
Complete Update on 06/04/1985
Created 19830315 by KC
GLCC
RELATED TOXIC SUBSTANCES FOUND IN THE CAMP POND AND CAMP WATER WELL 2003 AND
2004