TOLUENE
http://www.nycwasteless.com/gov-bus/citysense/e...
Acute Health Effects:
Contact can irritate skin and eyes. Inhalation can irritate nose and throat,
causing coughing and wheezing. Exposure can affect the nervous system, causing
trouble concentrating, headaches, slowed reflexes, loss of appetite, and nausea.
Higher levels can cause dizziness and lightheadedness, which can lead to
unconsciousness or death.
Chronic Health Effects:
May damage a developing fetus. Prolonged contact can cause drying, cracking,
itching, and a skin rash. Repeated exposure may cause liver, kidney, and brain
damage.
http://www.webcom.com/~bi/tables/health-effects-...
Toulene is a well known addictive substance. (Glue sniffing) It gives feelings
of intoxication. Causes sleepiness, dizziness, headache, muscular weakness,
confusion, impaired co-ordination, and visual impairment. It is neurotoxic
causing neurobehaivioral changes. Causes changes in Liver and kidneys, erosion
of the nose, degeneration of respiratory tract skin. Chronic abuse causes damage
to the brain in the cerebral area and causes brain stem atrophy.16
Causes reproductive toxity.15 Accumulates in blood and subcutaneous
fat if insufficient clearance time between exposures. Irritates eyes and upper
respiratory tract. Toulene intereacts with other human exposures such as alcohol
ingestion. Pattern recognition is disturbed, by both Alcohol and Toulene.
Toulene effects accuracy more than Alcohol. Toulene combined with Alcohol caused
performance and mood to decline more than for either one separately.
http://www.atsdr.cdc.gov/tfacts56.html
HIGHLIGHTS: Exposure to toluene occurs from breathing contaminated workplace
air, in automobile exhaust, some consumer products paints, paint thinners,
fingernail polish, lacquers, and adhesives. Toluene affects the nervous system.
Toluene has been found at 959 of the 1,591 National Priority List sites
identified by the Environmental Protection Agency (EPA).
How can toluene affect my health?
Toluene may affect the nervous system. Low to moderate levles can cause tiredness, confusion, weakness, drunken-type actions, memory loss, nausea, loss of appetite, and hearing and color vision loss. These symptoms usually disappear when exposure is stopped.
Inhaling High levels of toluene in a short time can make you feel light-headed, dizzy, or sleepy. It can also cause unconsciousness, and even death.
High levels of toluene may affect your kidneys.
How likely is toluene to cause cancer?
Studies in humans and animals generally indicate that toluene does not cause cancer.
The EPA has determined that the carcinogenicity of toluene can not be classified.
How does toluene affect children?
It is likely that health effects seen in children exposed to toluene will be similar to the effects seen in adults.
Some studies in animals suggest that babies may be more sensitive than adults.
Breathing very high levels of toluene during pregnancy can result in children with birth defects and retard mental abilities, and growth. We do not know if toluene harms the unborn child if the mother is exposed to low levels of toluene during pregnancy.
How can families reduce the risk of exposure to toluene?
Use toluene-containing products in well-ventilated areas.
When not in use, toluene-containing products should be tightly covered to prevent evaporation into the air.
TOLUENE
Human Health Effects:
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence for
the carcinogenicity of toluene in humans. There is
evidence suggesting lack of carcinogenicity of toluene
in experimental animals. Overall evaluation: Toluene is
not classifiable as to its carcinogenicity to humans (Group 3).
CLASSIFICATION: D; not classifiable as to
human carcinogenicity. BASIS FOR CLASSIFICATION: No human data and inadequate
animal data. Toluene did not produce positive results
in the majority of genotoxic assays. HUMAN CARCINOGENICITY DATA: None.
A4. A4= Not classifiable as a human
carcinogen.
Human Toxicity Excerpts:
Among 61 painters inhaling 100-1100 ppm toluene
for 2 wk to 5 yr, depressed erythrocyte counts with elevated hemoglobin, mean
corpuscular volumes, and elevated mean corpuscular hemoglobin were found in 5%
to 30% compared with groups of 73-395 workers not known to be exposed to toluene;
differential leukocyte counts were not significantly different between the toluene-exposed
and the reference workers.
... TOLUENE CAUSES
DEFATTING OF SKIN WITH SUBSEQUENT DANGER OF DRYNESS, FISSURING AND SECONDARY
INFECTION.
... SUDDEN DEATH AMONG "SNIFFERS"
MAY BE ATTRIBUTED TO LETHAL CARDIAC ARRHYTHMIAS FOLLOWING SENSITIZATION OF THE
MYOCARDIUM.
... PERMANENT ENCEPHALOPATHY ... /IN/ MAN WHO
INHALED TOLUENE REGULARLY FOR OVER 14 YR /WAS
DESCRIBED/.
VAPORS OF TOLUENE
CAUSE NOTICEABLE SENSATION OF IRRITATION TO HUMAN EYES AT 300-400 PPM IN AIR,
BUT EVEN AT 800 PPM IRRITATION IS SLIGHT. ... IN HUMAN VOLUNTEERS EXPOSED TO
CONCN AS HIGH AS 800 PPM ... DILATION OF PUPILS & IMPAIRMENT OF REACTION IN
ASSOCIATION WITH FATIGUE AT END OF 8 HR, ALSO SLIGHT PALLOR OF FUNDI.
Metabolic acidosis with a high "anion
gap" in 2 patients who had been sniffing toluene.
A report of 2 children who sniffed glue
containing toluene. One of the children became comatose
after an episode of "sniffing" which lasted for several hours. Adverse
effects included reduced appetite, nightmares, vertical nystagmus, and
incoordination.
WORKERS IN PHARMACEUTICAL PLANT IN FRANCE
EXPOSED TO TOLUENE DEVELOPED LEUKOPENIA, &
NEUTROPENIA. WITHIN 6 MO, THOSE AFFECTED SHOWED INCR IN CLOTTING TIME & DECR
IN PROTHROMBIN LEVEL ...
PERIPHERAL BLOOD LYMPHOCYTES FROM 32 MALE
ROTOGRAVURE WORKERS SHOWED NO SIGNIFICANT DIFFERENCE FROM CONTROLS IN FREQUENCY
OF CHROMOSOME ABERRATIONS & SISTER CHROMATID EXCHANGES.
Patients (3) with history of recurrent toluene
abuse were hospitalized and severe metabolic acidosis, electrolyte
abnormalities, hypoalkemia, and muscular weakness were present. Distal renal
tubular acidosis was believed to be present in 2/3 patients.
Child of a mother with a 14 year history of
solvent abuse showed symptoms of fetal alcohol syndrome.
A 27-year-old male developed cerebral and
cerebellar atrophy over a period of five years of extensive glue sniffing. He
also developed bilateral optic atrophy with blindness and severe sensorineural
hearing loss.
Toluene appears to
produce reversible effects upon liver, renal, and nervous systems. ... The
nervous system appears to be the most sensitive to the effects of toluene.
... High level toluene exposures produced
incoordination, ataxia, unconsciousness and eventually, death. Lower level acute
exposures in man produce dizziness, exhilaration and confusion. Activity level
has been inadequately studied. Schedule controlled behaviors have been reported
to produce inverted U-shaped concentration-effect curves on response rate
measures. Alterations at levels as low as 150 ppm have been reported when
appetitive contingencies are used. Very few studies of the nervous system have
been performed at levels below 1000 ppm and most of the results were
inconclusive. ...
Lethal levels 1.0 mg%; 10.0 ug/ml
IN EXPERIMENTS IN VITRO, TOLUENE
DID NOT CHANGE NUMBER OF SISTER-CHROMATID EXCHANGES OR THE NUMBER OF CHROMOSOMAL
ABERRATIONS IN HUMAN LYMPHOCYTES.
A 28 yr old painter who was believed to be a
habitual toluene sniffer was admitted to Chiba
Emergency Medical Center on several occasions. Symptoms included: Tremors of the
upper extremeties, staggering of gait, slurred speech, slight mental
deterioration, pendular nystagmus, bradycardia, mild tremor of the leg, action
myoclonus, and head and trunchal titubation. There was no dysmetria. The
involuntary movements were classified as hyperkinesie volitionnelle. Muscle tone
was hypotonic. Muscle weakness and atrophy were not seen. Deep tendon reflexes
were all exaggerated, but there was no pathological reflex. He showed wide-based
ataxic gait. Sensory and autonomic functions were normal. Blood, urine and
cerebrospinal fluid analysis appeared normal. Electroencephalography showed
40-50 uV, 9-10 c/s alpha waves with a few fast waves. Brain CT scan revealed a
moderate enlargement of the lateral and third ventricles. Surface
electromyography was performed on the proximal musculature of the arm. 3 c/s
reciprocal rhythmical grouping discharges were found at the terminal phase of
the elbow bending. The tremor was diminished by 20 minutes ischemic compression
test of the arm. With respect to therapy, clonazepam was useful for hyperkinesie
volitionnelle. He became able to drink a cup of water without spilling it by his
own hands, and was discharged from hospital on April 3rd, 1981. It was believed
that he was a habitual sniffer to toluene. On June
30th, 1983 he was found comatose. On admission to Chiba Emergency Medical
Center, his breath smelt of toluene. His blood toluene
level was 7.53 ppm, and urinary hippuric acid concentration was 9,500 mg/l. He
died on July 9th, 1983, because of disseminated intravascular coagulation,
multiple organ failure and perforation of the terminal ileum. Autopsy was
performed and neuropathological findings were as follows. 1) Diffuse
demyelination and gliosis of the cerebral and cerebella white matter. 2) Marked
loss of Purkinje cells of the cerebellum. 3) Astrocytic proliferation of the
dentate fugal system and inferior olivary nucleus of medulla. ...
Autopsy findings on a man who fell from a
height due to acute toluene poisoning while painting
are described. Gas chromatographic examination revealed that the toluene
concentrations of his blood, lung, liver and brain were 48, 35, 65 and 80 ug/g,
respectively. These toluene levels were not enough to
be definitely lethal, but were enough to anesthetize the central nervous system.
The psychological performance of 43
rotogravure printers exposed to a mean time- weighted average of 117 ppm toluene
for a mean time period of 21.7 yr was compared to that of 31 offset printers
with a mean working period of 23 yr. The offset printers were exposed to
mixtures of aliphatic hydrocarbons or ethyl acetate (amounts not given) for a
total of 10 to 60 min daily. Drinking habits were considered in grouping the
workers. The test battery consisted of standardized tests for verbal and visual
cognition and memory, perceptual motor speed, and psychomotor abilities.
Performances of the two printer groups were similar with rotogravure printers
having statistically significant lower scores on tests measuring visual
cognitive abilities. Mean test performances indicated that drinking habits did
not explain the impairment of visual cognitive abilities.
Acute poisoning may result from exposure to
high concn of toluene; A /CNS depressant/ effect is
produced. Human death has resulted from exposure to 10,000 ppm. Toluene
is more acutely toxic than benzene; however, severe blood disorders of the type
associated with benzene are not reported. Inhalation of 200 ppm has affected the
CNS in humans.
Vapors irritate eyes and upper respiratory
tract; Cause dizziness, headache, anesthesia, and respiratory arrest. Liquid
irritates eyes. If aspirated, causes coughing, gagging, distress, and rapidly
developing pulmonary edema. If ingested causes vomiting, griping, diarrhea, and
depressed respiration. Kidney and liver damage may follow ingestion.
In recent years some youngsters have been
indulging in what is called thinner inhalation, posing a serious social problem.
Organic solvents have also been widely used industrially as adhesives or
degreasing and rinsing agents, generating a kind of occupational disease which
has become a medical problem. Some school children who refuse to go to school
complaining of headache, head heaviness, blurred vision, diplopia, or dizziness,
may actually have toluene toxicosis caused by the
adhesive they use in constructing plastic models. /An examination of/ 35 such
patients neurogically, found some impairment in the cerebellar cortex,
cerebellar nuclei, or efferent pathways. This report is presented to invite
comments from other researchers.
Severe, acute toluene
intoxication in two workers was described. Special attention was paid to the
metabolism of toluene in man and to the choice of
reference parameters to monitor intoxication. The men had tiled a small swimming
pool to be used for exercise programs in a rehabilitation clinic. They had used
a special glue to make the joints of cement between the tiles resistant to
bleaching solution; the next day they removed the excess glue using toluene.
One worker was exposed for 2 hours and the other for 3 hours. Both were overcome
with the fumes, and were found lying at the bottom of the pool. Symptoms
included stupefaction, paresis, and amnesia. Patient-A had mucosal irritation of
the eyes and slurred speech. He was stuporose and unable to walk or sit. His
amnesia lasted for about 3 hours. Patient-B had mucosal irritation of the eyes,
was drowsy, and was just able to walk. He had normal speech and complained of
headache. The duration of his amnesia was about 2.5 hours. Solid evidence for toluene
exposure was provided by the blood toluene
concentration. The concentration 2 hours after exposure was 4.1 mg/l in
patient-A and 2.2 mg/l in patient-B.
The memory sequelae for a group of female
workers accidentally exposed to organic solvents were examined retrospectively
to evaluate complaints of residual memory impairment. The subjects included
seven employees (mean age 32.1 years) who agreed to retesting and who had been
severely intoxicated by exposure to toluene and
aliphatic hydrocarbons found in adhesives used in the manufacture of tennis
balls. They were compared to eight workers (mean age 33.7 years) who were
solvent exposed but not affected by the accident and ten workers (mean age 36.6
years) who had no exposure. Acute symptoms included faintness, nausea, vomiting,
and headache. Complaints of impaired memory, personality changes, and loss of
confidence persisted 8 months after exposure. Memory testing was first performed
2 months after exposure, with the follow up 6 months later to assess recovery.
The three memory tasks included paired associate task, serial position task, and
Brown-Peterson task. The subjects showed normal patterns of performance on tests
of learning and short term and long term memory, but demonstrated marked
difficulties when attention had to be divided between two resource competing
tasks. The clearest evidence of impairment was observed in the Brown-Peterson
task, where the acute group showed a significantly greater increase in word
recall omission after periods of counting backwards in threes. The magnitude of
the memory sequelae was not correlated with scores of self rated depression. It
was concluded that solvent intoxication can cause neuropsychological sequelae
lasting more than 8 months; memory tasks could prove useful in identifying
memory impairment in other occupationally exposed groups.
In a cross-sectional study of 181 male workers
of a rotogravure printing plant, most of whom were exposed to toluene
levels well above the GDR threshold limit values, 55 subjects revealed
pathological liver screening values (activities of serum aspartate
aminotransferase, alanine aminotransferase, gamma glutamyltransferase; liver
size). The differential diagnostic examination showed in 51 of these 55 subjects
an association with competing factors such as alcohol abuse (78%) and overweight
(40%), to a slight extent disorders of fat and carbohydrate metabolism and of
the gallbladder. Drug intake did not play any role. The variance and regression
analyses of the biochemical data have shown that alcohol significantly and
considerably increases the activities of all three enzymes tested. Bodyweight
had a similar, but less pronounced, significant effect. On the other hand, in
subjects with a higher alcohol intake the activities of liver enzymes in highly toluene
exposed subgroups were significantly and clearly lower than among slightly toluene
exposed workers.
General health effects include lethality,
growth, morbidity, liver and kidney damage and miscellaneous effects.
Neurobehavioral effects include epidemiological and clinical findings, activity
and sleep, performance and learning, electrophysiological effects. Evaluation
and synthesis of data is included. It was concluded that low level exposure to toluene
has its primary effect on the CNS. From a systematic or general point of view it
is not clear what this effect is. Both depressant and excitatory effects
(possibly concentration dependent) were reported as well as other kinds of
results. Other health effects were not life threatening at any exposure level
short of that producing lethality. Effects were reversible even at extremely
high exposure levels for very long durations.
Toluene embryopathy
is characterized by microcephaly, central nervous system dysfunction,
attentional deficits and hyperactivity, developmental delay with greater
language deficits, minor craniofacial and limb anomalies, and variable growth
deficiency. Previously, three affected children, born to women who inhaled toluene
regularly throughout pregnancy, have been reported. Two more cases are described
emphasizing the importance of toluene as a potential
human teratogen.
Neurobehavioral tests were undertaken by 30
female workers exposed to toluene and matched controls
with low occupational exposure to toluene. The
environmental air levels (TWA) of toluene was 88 ppm
for the exposed workers and 13 ppm for the controls. The toluene
in blood concentrations for the exposed workers was 1.25 mg/l and for the
controls 0.16 mg/l. Statistically significant differences between workers
exposed to toluene and controls in neurobehavioral
tests measuring manual dexterity (grooved peg board), a visual scanning (trail
making, visual reproduction, Benton visual retention, and digit symbol), and
verbal memory (digit span) were observed. Further, the performance at each of
these tests was related to time weighted average exposure concentrations of air toluene.
The workers exposed to toluene had no clinical symptoms
or signs. The question arises as to whether these impairments in neurobehavioral
tests are reversible or whether they could be a forerunner of more severe
damage.
When compared with benzene, toluene
has little to no effect on immunocompetence. However, it should be noted that toluene
exposure effectively attenuates the immunotoxic effects of benzene (probably
because of competition for metabolic enzymes).
Neutral organic solvents such as ... toluene
... cause pain on contacting the eye, and examination after a generous splash of
solvent shows dulling of the cornea. The epithelium will show punctate staining
with fluorescein. The damage appears to be scattered loss of epithelial cells
due to solution of some of the fats that occur in these cells.
Toxicities associated with toluene:
CNS depression, syncope, coma, cardiac arrhythmias and sudden death, ataxia,
convulsions, rhabdomyolysis, increased creatine phosphokinase, abdominal pain,
nausea, vomiting, hematemesis, peripheral neuropathy, paresthesias,
encephalopathy, optic neuropathy, cerebella ataxia, distal renal tubular
acidosis, hyperchloremia, hypokalemia, azotemia, hypophosphatemia, hematuria,
proteinuria, pyruria, normalities, decreased cognitive function, fatal overdose.
/From table/
Women workers exposed to high air
concentrations of toluene (50-150 ppm) appeared to have
a higher incidence of spontaneous abortion than a similar group of women with no
occupational exposure to toluene.
Maternal spray paint or glue sniffing leads to
maternal complications including renal tubular acidosis, hypokalemia,
hypocalcemia, cardiac arrhythmias, rhabdomyolysis, and premature labor.
Premature toluene exposure leads to a characteristic
pattern of anomalies similar to findings in infants exposed to alcohol in utero,
consisting of an increased incidence of malformations, poor growth, and
developmental delays.
Eye and upper airway irritation occurred after
a 6.5 hr exposure to an air level of 100 ppm (377 mg/cu m) toluene,
and lachrymation was seen at 500 mg/cu m.
Volunteers exposed to 100 ppm (377 mg/cu m) toluene
for 6 hr/day for four days suffered from subjective complaints of headache,
dizziness and a sensation of intoxication. In subjects exposed to 750 mg/cu m
for 8 hr, fatigue, muscular weakness, confusion, impaired coordination, enlarged
pupils and accommodation disturbances were experienced; at about 3000 mg/cu m,
severe fatigue, pronounced nausea, mental confusion, considerable incoordination
with staggering gait and strongly affected pupillary light reflexes were
observed. After exposure at the high level, muscular fatigue, nervousness and
insomnia lasted for several days. Heavy accidental exposure leads to coma.
Humans exposed to concentrations of toluene
of between 200-800 ppm may experience respiratory and ocular irritation.
Children with microcephaly, minor craniofacial
and limb anomalies, central nervous system defects, attention disorders,
developmental delay, learning disorders, and language deficits were born to
mothers who abuse toluene by inhalation during
pregnancy.
Controlled exposure effects on volunteers were
studied at toluene concentrations ranging from 40, 60,
or 100 ppm. ... Psychologic measurements indicated decrements in vigilance,
visual perception, motor performance, and ability to carry out functions at 100
ppm.
Acute effects in humans following exposure to toluene:
50-100 ppm: subjective complaints (fatigue or headache), but probably no
observable impairment of reaction time or coordination; 200 ppm: mild throat and
eye irritation; 100-300 ppm: detectable signs of incoordination may be expected
during exposure periods up to 8 hr; 400 ppm: lacrimation and irritation to the
eyes and throat; 300-800 ppm: gross signs of incoordination may be expected
during exposure periods up to 8 hr; 1500 ppm: probably not lethal for exposure
periods of up to 8 hr; 4000 ppm: would probably cause rapid impairment of
reaction time and coordination, exposures of one hr or longer might lead to /CNS
depression/ and possibly death; 10,000-30,000 ppm: onset of /CNS depression/
within a few minutes, longer exposures may be lethal. /From table/
Studies of women exposed to solvents such as
benzene, toluene, and xylene have shown menstrual
disturbances, principally associated with abnormal bleeding.
FROM THE STANDPOINT OF CHRONIC EXPOSURE, IT IS
CLEAR THAT TOLUENE DOES NOT CAUSE THE SEVERE INJURY TO
THE BONE MARROW THAT IS CHARACTERISTIC OF BENZENE POISONING.
Toluene abuse (to
10,000 ppm) has been linked with kidney disease as evidenced by blood (hematuria),
protein (proteinuria), albumin (albuminuria), and pus (pyuria) in the urine,
accompanied by elevated serum creatinine, decreased urinary output, and
metabolic and renal tubular acidosis.
... The highest toluene
concentrations in air that could be tolerated for 3.5-6 hr without measurable
decrements on behavioral test performance were 80 ppm to 100 ppm.
The pregnancies of four of five women
associated with gross toluene abuse (0.5 to 2 cans of
spray paint/day for 6 mos to 11 yr) resulted in evidence of renal toxicity (as
evidenced by severe renal tubular acidosis), fetal toxicity (manifest as
intrauterine growth retardation), and teratogenicity (deformed external ears,
ventricular septal defect, micrognathia, hydronephrosis) with facial features
reminiscent of the FAS (short palpebral fissures, epicanthal folds, maxillary
hypoplasia).
In a case study of two adult white males who
suffered from toluene intoxication while removing glue
from tiles in a swimming pool, cardiac arrhythmias were noted. Response seemed
to be highly variable among individuals. One person exposed for 2 hr to less
than 1890 ppm toluene exhibited a rapid heartbeat
(sinus tachycardia), while the second person, exposed for 3 hr, exhibited a slow
heartbeat (bradycardia).
Severe renal tubular acidosis was observed in
five pregnant women who were chronic abusers of paints containing toluene.
Exposure of students to 75 or 150 ppm toluene
for 7 hr caused a dose-related impairment of function on digit span, pattern
recognition, the one hole test, and pattern memory. There was an effect on the
results of the symbol digit test but the effect was not dose related. Subjects
served as their own controls. ... There were no differences in the results on
simple reaction time, POMS mood scale, visual memory, hand-eye coordination,
Sternberg test, finger tapping, reaction time, continuous performance test, and
critical tracking test.
A group of 95-104 workers exposed to TWA of
41-46 ppm toluene during shoemaking, printing, and
audio equipment production were evaluated for symptoms and signs of exposure
when compared to 130 control subjects. The incidence of health-related
complaints among the toluene exposed workers was two to
three times that of the controls. Dizziness was reported by about two-thirds of
the toluene exposed respondents. These subjects also
complained of headaches, sore throats, eye irritation, and difficulty with
sleep. When the exposed subjects were divided into two groups, one with TWA
exposures of less than 40 ppm and the other with exposures greater than or equal
to 40 ppm, the incidence of headache and sore throat, but not dizziness, showed
a dose-response pattern.
Children born to toluene
abusers have exhibited renal tubular acidosis immediately after birth due to
hyperchloremia. In each incident the acidosis was resolved within 3 days of
birth.
Several case series have demonstrated that
high exposure to toluene through sniffing during
pregnancy induces a syndrome that closely resembles the fetal alcohol syndrome,
with pre- and postnatal growth deficiency, microcephaly and developmental delay,
typical craniofacial features including micrognathia, small palpebral fissures,
and ear anomalies.
Renal tubular acidosis is one of a number of
human complications reported in the offspring of mothers inhaling toluene
during pregnancy. This article reports a case of a premature newborn with renal
tubular acidosis probably due to maternal sniffing of paint containing toluene.
Characteristics of this condition are described as well as its medical
management.
Skin, Eye and Respiratory Irritations:
A human eye irritant. An experimental skin and
severe eye irritant.
Medical Surveillance:
Yearly physical examinations of exposed
personnel, with special attention to the eyes and central nervous system,
including complete blood count and liver function tests.
The clinical examination should include
hemocytometric testing and a thrombocyte (platelet) count in view of the
possibility that toluene may contain a certain
proportion of benzene.
Hippuric acid levels above 5 g/l of urine may
result from exposure greater than 200 ppm determined as a time weighted average.
Populations at Special Risk:
Preclude individuals from exposure to toluene
who have central nervous system or liver diseases.
Probable Routes of Human Exposure:
NIOSH (NOES Survey 1981-1983) has
statistically estimated that 1,625,598 workers (288,299 of these are female) are
potentially exposed to toluene in the US(1).
Occupational exposure to toluene may occur through
inhalation and dermal contact with this compound at workplaces where toluene
is produced or used(SRC). The general population may be exposed to toluene
via inhalation of ambient air, ingestion of food and drinking water, handling of
gasoline, and exposure to some consumer products where toluene
is used as a solvent(SRC).
Toluene was detected
in hairdresser salons in Norway at concns of 0.04-0.11 mg/cu m(1). The time
weighted average (TWA) of toluene in the workplace air
of a municipal waste composting facility was reported as 188,000 ug/cu m(2). In
a 1989 Danish survey on chemical exposures(3), the number of worker exposure
events for toluene were documented: manufacturing of
metals, 420; manufacturing of metal fabricated products 64,000; electrical
machinery and apparatus, 1,500; manufacture of transport equipment 2,700;
painters and carpenters 15,000; construction workers, 5,400; publishing and
printing, 6,300; wholesale trades, 5,000; textile and leather manufacturing,
4,400; wood and furniture manufacturing, 5,900; manufacture of chemicals, 8,700;
manufacture of paints and petroleum, 1,400; manufacture of non-metallic mineral
products, 2,300; manufacture of optical instruments, 2,500 manufacture of
plastic and boat building, 1,100; sewage and refuse disposal, 99; agriculture
and forestry, 11,000; health services, 2,600. The total number of work related
exposure events was 140,000(3). Toluene was detected in
the workplace air of glass fiber manufacturing plants and high temperature
sealing component and clutch lining plants at a mean concn of 65 ppm(4).
Body Burden:
Toluene was
identified, not quantified, in 8 samples of mothers' milk from 4 urban areas(1).
Toluene was detected in 250 of 250 specimens of human
blood at concns of 0.2-38 ppb (1.5 ppb avg)(2). Toluene
was detected in 91% of the samples of the National Human Adipose Tissue Survey
at a max concn of 250 ppb(3). Toluene was identified,
not quantified, in expired breath of people at service stations during
fueling(4). The mean concn of toluene in the blood of
non-occupationally exposed individuals in the US was 0.52 ppb(5). The avg concn
of toluene in the blood and urine of workers in glass
fiber and clutch lining plants were 911 ug/l and 2.9 mg/l, respectively(6).
Average Daily Intake:
AIR INTAKE (assume median concn 11 ppb(1)) 843
ug; WATER INTAKE (assume 2 ppb(2)) 4 ug; FOOD INTAKE - insufficient data.
Minimum Fatal Dose Level:
Ingestion of approximately 60 ml (625 mg/kg)
of toluene proved fatal for a while male mental
patient.
Antidote and Emergency Treatment:
Basic treatment: Establish a patent airway.
Suction if necessary. Watch for signs of respiratory insufficiency and assist
ventilations if necessary. Administer oxygen by nonrebreather mask at 10 to 15
L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for
shock and treat if necessary ... . For eye contamination, flush eyes immediately
with water. Irrigate each eye continuously with normal saline during transport
... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up
to 200 ml of water for dilution if the patient can swallow, has a strong gag
reflex, and does not drool. Administer activated charcoal ... . /Aromatic
hydrocarbons and related compounds/
Advanced treatment: Consider orotracheal or
nasotracheal intubation for airway control in the patient who is unconscious or
in respiratory arrest. Positive-pressure ventilation techniques with a
bag-valve-mask device may be beneficial. Monitor cardiac rhythm and treat
arrhythmias if necessary ... . Start an IV with D5W /SRP: "To keep
open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia
are present. Watch for signs of fluid overload. Consider drug therapy for
pulmonary edema ... . Treat seizures with diazepam (Valium) ... . Use
proparacaine hydrochloride to assist eye irrigation ... . /Aromatics
hydrocarbons and related compounds/
Animal Toxicity Studies:
Evidence for Carcinogenicity:
Evaluation: There is inadequate evidence for
the carcinogenicity of toluene in humans. There is
evidence suggesting lack of carcinogenicity of toluene
in experimental animals. Overall evaluation: Toluene is
not classifiable as to its carcinogenicity to humans (Group 3).
CLASSIFICATION: D; not classifiable as to
human carcinogenicity. BASIS FOR CLASSIFICATION: No human data and inadequate
animal data. Toluene did not produce positive results
in the majority of genotoxic assays. HUMAN CARCINOGENICITY DATA: None.
A4. A4= Not classifiable as a human
carcinogen.
Non-Human Toxicity Excerpts:
A TEMPORARY INCOORDINATION WITH MUSCULAR
TREMORS HAS BEEN OBSERVED IN PUPPIES & KITTENS & IN DOGS AT TWICE
THERAPEUTIC DOSE LEVEL. CALVES IN POOR CONDITION SHOWED STAGGERING GAIT AND SOME
COLLAPSED BUT RECOVERY WAS COMPLETE AFTER UP TO 4 HOURS. FOUR TIMES THERAPEUTIC
DOSE RATE PRODUCED NO OBSERVABLE CHANGES IN ... ORGANS.
... /CNS DEPRESSANT/ EFFECT OF TOLUENE
... IS EXERTED IN 2 PHASES--A PRELIMINARY ... /CNS DEPRESSION/ FOLLOWED BY STAGE
OF EXCITEMENT, MANIFESTED BY TREMOR, MUSCULAR CRAMPS AND DISTURBANCES IN
BEHAVIOR ...
... SWELLING OF GLOMERULI, CYLINDERS &
ALBUMIN IN URINE IN 2 ... DOGS. BUT ... /INVESTIGATORS/ NOTE THAT THE DOGS WERE
OF BREED WHICH FREQUENTLY DEVELOP INTERSTITIAL NEPHRITIS. ... HEMORRHAGIC &
DEGENERATIVE LESIONS IN GOATS.
IN DOGS ... CONGESTION & HEMORRHAGIC FOCI
WERE PRESENT IN LIVER; THESE LESIONS ... ALSO PRESENT IN GOATS ... CONGESTION
& SOME ALVEOLAR INFLAMMATION /OF LUNG ALSO/ ... IN DOGS & ... GOATS.
SPLEEN ... SHOWED SOME DIMINUTION OF LYMPHOID FOLLICLES & PLAQUES OF
HEMOSIDEROSIS.
EFFECTS IN CATS EXPOSED TO 7800 PPM (31.0
MG/L)/6 HR: CNS EFFECTS, MYDRIASIS, MILD TREMORS, PROSTRATION IN 80 MIN, LIGHT
ANESTHESIA IN 2 HR. /FROM TABLE/
INTRATRACHEAL ADMIN /TO CATS/ WITH CHRONICALLY
IMPLANTED ELECTRODES INDUCED SEIZURES ALONG WITH BEHAVIORAL DISTURBANCES SUCH AS
NODDING, TWITCHING & APPARENT HALLUCINATIONS.
... RATS /EXPOSED/ TO 1500 MG/CU M OF AIR FROM
DAY 1 THROUGH 8 OR 1000 MG/CU M FOR 8 HR DAILY FROM DAY 1 THROUGH DAY 21 /OF
GESTATION/ ... /WITH/ NO TERATOGENIC EFFECT. SOME FETAL GROWTH RETARDATION ... @
HIGHER DOSE ... MICE WERE EXPOSED DURING DAYS 6-13 TO 1500 MG/CU M OF AIR WITH
SIMILAR RESULTS.
/GAVAGING/ MICE /WITH/ 1.0 MG/KG ON DAYS 6
THROUGH 15 /OF GESTATION/ ... INCR CLEFT PALATE IN THE OFF-SPRING.
TOLUENE WAS UNABLE TO
REVERT SALMONELLA TYPHIMURIUM STRAINS TA1535, TA1537, TA1538, TA98 AND TA100 IN
THE AMES SALMONELLA/MICROSOME ASSAY, EITHER WITH OR WITHOUT METABOLIC ACTIVATION
BY S9 MIX FROM LIVERS OF RATS EITHER UNTREATED OR INDUCED WITH AROCLOR 1254.
FOLLOWING IP ADMIN OF 1 ML TOLUENE/KG
DAILY FOR 21 DAYS TO RATS, MIXED-FUNCTION OXYGENASE ACTIVITY INCREASED 33.8% IN
LIVER BUT WAS UNCHANGED IN BRAIN.
TOLUENE & M-XYLENE
CAUSED MUSCULAR WEAKNESS & EQUILIBRIUM DISTURBANCES IN THE RAT FOLLOWING IP
ADMIN. THE LOCOMOTOR (OPEN-FIELD BEHAVIOR) & RUNNING ACTIVITY
(WHEEL-RUNNING) IN THE RAT WAS MOST AFFECTED BY TOLUENE.
THESE DIFFERENCES WERE RELATED TO THE DIFFERENCES IN THE STIMULATORY EFFECTS OF
THE SOLVENTS ON THE CNS.
RATS WERE EXPOSED TO TOLUENE
OR N-HEXANE OR A MIXT OF THE 2 CMPD AT 1000-8000 PPM FOR 8 HR. ACETYLCHOLINE WAS
INCR AT LOW CONCN OF THE SOLVENTS, BUT WAS GREATLY DECR AT HIGH CONCN. CHOLINE
ACETYLTRANSFERASE WAS DECR SIGNIFICANTLY AT HIGH CONCN OF THE MIXT.
ACETYLCHOLINE ESTERASE ACTIVITY WAS INCR BY THE SOLVENTS.
In skin painting studies with CF1, CH, and BaH
strains of mice, 0.05 to 0.1 ml/mouse was applied to 25 mice/sex/strain for 52
weeks. Results were negative for tumor development.
Intraperitoneal admin of 250, 500, or 1,000
mg/kg at 0 and 24 hr failed to give positive results in micronucleus test with
Swiss mice.
... Groups of rats were trained on the
conditioned avoidance response task during the last week of a 5 week exposure to
1400 or 1200 ppm toluene (14 hr/day, 7 days/week) or
during the first or third weeks after the exposure ended. None of the three
groups ... were able to acquire the auditory condition avoidance response ... .
Subsequent tests ... revealed that hearing with these rats was unimpaired at 4
KHz, slightly impaired at 8 KHz, and markedly impaired at 12 KHz and above.
Pregnant CD-1 mice were housed singly in
multicompartment cages in inhalation chambers and exposed to toluene
at a concentration of 0, 750, or 1500 mg/cu m (0, 200, or 400 ppm) for 7 hrs/day
from day 7 through day 16 of gestation. The mice were killed on day 17 of
gestation and the fetuses were removed and examined. Maternal weight gain was
not affected by toluene exposure but the liver to body
weight ratio was significantly reduced. The treated dams showed no significant
differences in the average number of implantation sites, number of live fetuses,
fetal mortality, or fetal body weight at either toluene
concentration compared to control values. The incidence of enlarged renal pelvis
was significantly greater in fetuses exposed to 200 ppm than in the fetuses
exposed to 400 ppm or in the controls. A shift in rib profile (number of fetuses
with 13 ribs) was observed in the higher toluene
concentration group, and this shift was significantly different from the rib
profile of controls. There was an increase in the total activity of lactic
dehydrogenase activity in the brain of the dams from the 400 ppm group. The
total activity of lactic dehydrogenase in the toluene
exposed pups did not differ significantly from the controls for liver, heart,
lung, or kidney, but the brain lactic dehydrogenase activity of the treated
group was slightly greater than the control value.
Behavioral toxicity of toluene
was assessed in mice confined in a 20 liter hermetically sealed chamber for
several hours. Toluene was introduced through a port
and volatilized by a hot plate. Samples of chamber air for analysis were taken
through another port. A smaller mesh cage held the mouse within the larger
chamber. Schedule-controlled responding was developed by arranging that a
response, breaking a beam of light, was followed by mild (under an F1 60 sec)
schedule. Responding was much more rapid in the presence of stimuli correlated
with the F1 schedule than when the schedule was not operating. Standard sessions
consisted of alternating series of 8 consecutive F1 60 sec and inter-series 30
min time-outs. Concentration-effect curves were determined by exposing a mouse
to incremental additions of toluene at 30 min
intervals. Toluene increased the rate of responding in
most mice at levels of about 700 ppm. Higher concentrations progressively
reduced responding. The ED50 (the concentration reducing responding by 50%)
averaged 1657 ppm in 10 mice. It is estimated that there is a 1/1000 chance
/ED001/ of the responding of a mouse being reduced by as much as 10% by a
concentration of toluene of 69 ppm.
Sixteen rats were chronically implanted with
bipolar electrodes in the hipocampal regions containing cells generating
electric theta-activity. The animals were divided into 4 groups of which 2 were
exposed to 500 ppm of toluene in inhalation chambers,
for 8 or 16 hours per day for 5 days per week in 12 weeks respectively, and 2
served as controls. The hippocampal electric activity was recorded 48 hours
after each weekly exposure. Frequencies of theta-activity in the exposed groups
were found to differ from their respective control group by variance analysis.
Each point on the frequency versus time plot were further analysed by Student's
t-test. Compared to the non-exposed group the eight hours daily exposed showed
an initial period of increased frequency of the regular theta-waves together
with an increased incidence of theta-activity after 1-2 weeks of exposure. In
the sixteen hours daily exposed rats two weeks of toluene
inhalation produced a significant reduction in the theta-wave frequency. This
change was also reached after either weeks of exposure in the eight hours daily
exposed group. At this moment the theta-activity was frequency disrupted by
short amplitude irregular waves, a phenomen which increased gradually throughout
the rest of the exposure period. The average blood concentration of toluene
was 16.7 ug/ml and 17.7 ug/ml and not significantly different for the eight and
sixteen hours exposed groups respectively.
The effects of toluene
vapors on brain lipid changes were investigated in male Sprague-Dawley rats. The
animals (8/group) were continuously exposed to 320 ppm toluene
for 30 days. Controls were exposed to air. Exposed animals showed decreased body
weight (p< 0.01), decreased brain weight (p< 0.01), and a decrease in the
weight of the cerebral cortex (p< 0.05) when compared to controls. In the
cerebral cortex of exposed rats, total phospholipids was reduced (p< 0.001),
there was an increase in phosphatidic acid (p< 0.05) and a decrease in a
minor fatty acid of ethanolamine phosphoglyceride (p< 0.05). No changes in
lipids were found in the brain stem.
With the intention of investigating possible morphological alterations
With the intention of investigating possible
morphological alterations effected by toluene in the
developing CNS, rat pups were exposed to 100 ppm and 500 ppm of atmospheric toluene
from postnatal day 1 until sacrifice at postnatal day 28, when the hippocampal
region (area dentata, Ammon's horn, subiculum) was examined by light microscope
and alterations in the volumes of the layers of the subdivisions were
determined. The layers of Ammon's horn and the subiculum were not affected
qualitatively or quantitatively by the 500 ppm exposure. Within the area dentata,
the volume of the granule cell layer was 6% smaller in animals exposed to 100
ppm and 13% smaller in animals exposed to 500 ppm than they were in controls.
The volumes of the hilus, which is a terminal field of granule cell axons, and
the commissural-association zone of the dentate molecular layer, which is the
terminal field of the hilar projection to the granule cells, were smaller (12%
and 19%) in animals exposed to 500 ppm than they were in controls. Argyrophilic
cells were found in the granule cell layer of all animals exposed to 500 ppm.
Pronounced granule cell degeneration was found in one animal exposed to 500 ppm.
The granule cell layer of animals exposed to 100 ppm appeared qualitatively
normal. The alterations reported here support the few earlier reports of
morphological alterations in the CNS of adult laboratory animals. Effects of toluene
similar to those described, that is alterations in specific neuron populations
and their afferent and efferent terminal fields may complement changes in
neurophysiology and behavior that have been observed in prenatally and
perinatally exposed rodent pups. Causal relationships, however, remain to be
elucidated.
The aim of the present study was to
investigate the effects of toluene on fetal development
in well nourished and malnourished rats. Long-term behavioral consequences after
in utero exposure were also studied. Toluene (1.2 g/kg
sc) was administered daily to well nourished and to malnourished (food
restricted to 50% of ad libitum intake) pregnant rats, during the second (8-15
days) or the third week of pregnancy (14-20 days). Offspring were evaluated for
malformation, development of the skeleton, prenatal growth of the brain and
liver, postnatal growth and long lasting behavioral effects. In utero exposure
to toluene during the third week of pregnancy resulted
in low body weight at birth, which persisted in the male offspring into
adulthood. Malnutrition increased fetal susceptibility to the effects of toluene
as indicated by evaluation of the development of the skeleton. Behavioral tests
performed when the pups were 30 and 90 days old showed effects of in utero
malnutrition (increased ambulation and worse performance in a shuttle box), but
no behavioral effects related to toluene exposure were
detected. These data indicate that in utero exposure to toluene
can have long lasting effects on body growth and that maternal malnutrition
increases the risk for toluene fetotoxicity.
Toluene did not
induce gene mutations in Salmonella typhimiurium strain TA98, TA100, TA1535, or
TA1537 with or without exogenous metabolic activation. In the mouse lymphoma
assay, toluene gave an equivocal response with and
without exogenous metabolic activation. Toluene did not
induce sister chromatid exchanges or chromosomal aberrations in Chinese hamster
ovary cells in the presence or absence of exogenous metabolic activation.
... Toluene can alter
learned behavior at concentrations below anesthetic levels but, in general,
above 1000 ppm.
Toluene was injected
into the yolk sac of fresh fertile chicken eggs prior to incubation.
Hatchability of the eggs was 85%, 25%, and 0 with exposures of 4.3, 8.7, and
17.4 mg/egg, respectively.
Toluene was reported
to induce chromosomal aberrations in the bone marrow cells of male albino rats
after chronic inhalation exposure to 5.4 or 50.7 mg/cu m on 4 hr/day, five
days/wk for four months or after sc injection of 0.8 g/kg bw. Chromosomal
aberrations in bone marrow cells were reported following sc injection of 1 g/kg
bw daily for 12 days to male albino rats.
Toluene and benzene
administered concurrently were reported to have an additive effect on induction
of chromosomal aberrations. Toluene reduced the number
of sister chromatid exchanges induced by benzene when both compounds were
administered intraperitoneally to DBA/2 mice and reduced the clastogenic
activity of benzene when the two compounds were simultaneously administered
orally to CD-1 mice, intraperitoneally to Sprague-Dawley rats, or subcutaneously
to NMRI mice.
Animal studies in mice exposed to toluene
at concentrations of 2.5-500 ppm demonstrated decreased host defense to
respiratory infections.
The cardiovascular response of 25 mongrel dogs
following exposure to 30,000 ppm toluene for 9-10 min
was complex. For most of the animals, there was no change in electrocardiogram
readings for the first 3-4 min of exposure. The heartbeat then became rapid for
several minutes, and was followed by a period of bradycardia. Immediately before
death ventricular fibrillation was noted. ... Four of the dogs were particularly
sensitive, their ventricular arrhythmias were transient and accompanied by
fluctuations of blood pressure. The authors suggested that toluene
had a direct effect on the septal and ventricular muscles of the heart which
permitted the development of fatal arrhythmias in sensitive dogs.
Mice exposed for 3 hr to toluene
at concentrations of 2.5-500 ppm exhibited increased, but not dose-related,
susceptibility to respiratory infections when challenged by Streptococcus
zooepidemicus. Pulmonary bactericidal activity was decreased at concentrations
of 2.5 ppm and 100-500 ppm but not at concentrations of 5-50 ppm. There was no
effect on susceptibility to infection with a toluene
exposure of 1 ppm for 3 hr, 5 days (3 hr/day) or 4 wk (3 hr/day). The
bactericidal activity of the lung was decreased during the 5-day treatment but
not with the 4-wk treatment. The authors hypothesized that toluene
exerted an adverse effect on alveolar macrophage function, thereby decreasing
disease resistance.
Studies have demonstrated that toluene
can produce subtle changes in the auditory system. Intermediate exposure to toluene
produced a permanent loss of hearing in the high frequency range (approximately
16 kHz) in rats exposed to 1200 ppm for 5-9 wk or 1000 ppm for 2 wk.
In 3-day-old rats, daily 15 min exposures to toluene
resulted in a dose-related increase in righting-reflex latency time. At each
dose the righting-reflex latency decreased over the first 4 wk of exposure
indicating that the animals had developed at least partial tolerance to the toluene.
During the second 4-wk period, latencies increased again at the higher doses but
were never as great as they were for the initial toluene
exposure. The results for the second 4-wk period showed that there were
limitations to the adaptive response at the higher toluene
doses and that there were cumulative effects of exposure at these doses.
Tolerance was probably the result of induction of toluene
metabolizing enzymes.
Concentrations of 480 ppm and above decreased
the ability of trained rats to perform a sequence of lever press actions
associated with a reward (milk). During training, the rats were divided into two
groups. The reward presentation for one group was not accompanied by any
noticeable external events. For the second group, the reward presentation was
accompanied by light and sound stimuli. The effects of toluene
on performance were less severe with the rats trained using the light and sound
reinforcement. This suggests that behavior associated with external signals is
less subject to disruption by toluene than behavior
that is not accompanied by external reinforcement.
Age ... influences neurological response after
exposure to toluene. Young rats (50 days old) were
affected by toluene to a lesser extent than older rats
(120 days old) based on several measurements of escape latency 30 days after
exposure to 30,000-40,000 ppm for 15 min/day.
Toluene exposure ...
changes sleep patterns in animals. Both single episodes of toluene
exposure (about 1000 ppm) and subchronic 8 hr/day exposures for 3 wk (about 600
ppm), changed patterns of sleep and wakefulness in rats. After the single
exposures, there was a decrease in wakefulness and an increase in slow-wave
sleep; a prolonged sleep latency was apparent for the 2 days following exposure.
Latency was defined as the time interval between the end of the exposure period
and the beginning of a particular phase of the sleep cycle. Following the 3 wk
exposures, there was an increase in wakefulness during the dark period on the 2
days after exposure and a decrease in slow wave sleep on the first day.
Brain levels of norepinephrine, dopamine,
serotonin, vanillylmandelic acid, homovanillic acid, and 5-hydroxyindolacetic
acid were altered in six areas of the brain in male CD-1 mice administered toluene
(5-105 mg/kg/day) in their drinking water for a 28-day period. Significant
increases of norepinephrine, dopamine, and serotonin were present in the
hypothalamus at all dose levels. The maximum increase occurred with the 22
mg/kg/day dose and there were lesser increases for both the 5 and 105 mg/kg/day
doses, giving biphasic response. Roughly similar fluctuations were seen in the
concentrations of vanillylmandelic acid and homovanillic acid, which are
metabolites of dopamine and norepinephrine and 5-hydroxyindolacetic acid, a
serotonin metabolite. In corpus striatum, the levels of dopamine and serotonin
were significantly increased at the two highest doses. The level of
vanillylmandelic acid was also increased significantly at the same doses. In the
medulla oblongata, the concentrations of norepinephrine, vanillylmandelic acid,
and 5-hydroxyindolacetic acid were significantly increased at the 22 mg/kg/day
dose, but not at the other doses, while the levels of serotonin were
significantly increased at the 22 and 105 mg/kg/day doses. Norepinephrine
concentrations were elevated in the midbrain. ...
To identify the frequency range most sensitive
to toluene-induced auditory damage, the auditory
function of adult Long-Evans rats exposed to 1750 ppm of toluene
(6 h/day, 5 days/week, 4 weeks), was tested by recording auditory-evoked
potentials directly from the round window of the cochlea. The present
electrocochleographic findings do not support a specific mid- to high-frequency
loss of auditory sensitivity. On the contrary, the electrophysiologic data,
obtained for audiometric frequencies ranging from 2 to 32 kHz, showed a hearing
deficit not only in the mid-frequency region (12-16 kHz), but also in the
mid-low-frequency region (3-4 kHz). Actually, the effect of toluene
was independent of the frequency in our experimental conditions. Histological
analysis was consistent with electrophysiologic data because a broad loss of
outer hair cells occurred in both mid- and mid-apical coil of the organ of Corti.
National Toxicology Program Studies:
Long-term studies were conducted by exposing
groups of 60 rats /F344/N/ of each sex to 0, 600, or 1,200 ppm toluene
by inhalation, 6.5 hours per day, 5 days per week. Groups of 60 /B6C3F1/ mice of
each sex were exposed at 0, 120, 600, or 1,200 ppm on the same schedule. ...
Animals were exposed to toluene for 103 weeks.
Nephropathy was seen in almost all rats, and the severity was somewhat increased
in exposed rats. A rare renal tubular cell carcinoma in a female rat and an
equally uncommon sarcoma of the kidney in another female rat were seen in the
1,200 ppm exposure group. Erosion of the olfactory epithelium and degeneration
of the respiratory epithelium were increased in exposed rats. Inflammation of
the nasal mucosa and metaplasia of the olfactory epithelium were increased in
exposed female rats. A rare squamous cell carcinoma of the nasal mucosa was seen
in one female rat at 1,200 ppm. A squamous cell papilloma of the forestomach was
observed in one female rat at 1,200 ppm, and a squamous cell carcinoma was
observed in a second female rat at 1,200 ppm. No chemically related neoplasms
were found in male rats, and the one nasal, two kidney, and two forestomach
neoplasms observed in female rats were considered not to be associated with
inhalation exposure to toluene. For mice, no biological
important increases were observed for any nonneoplastic or neoplastic lesions.
Non-Human Toxicity Values:
LD50 Rat oral 2.6 to 7.5 g/kg
LD50 Rabbit dermal 14.1 ml/kg
LD50 Rat (female) ip 1.64 g/kg
LD50 MOUSE IP 1.15 G/KG
LD50 Rat oral 5000 mg/kg
LD50 Rat ip 1332 mg/kg
LD50 Rat iv 1960 mg/kg
LC50 Mouse ihl 400 ppm/24 hr
LD50 Mouse ip 59 mg/kg
LD50 Mouse sc 2250 mg/kg
LD50 Mouse ip 640 mg/kg
LD50 Rabbit skin 12,124 mg/kg
... The LC50 for toluene
in mice is 5320 ppm/8 hr /via inhalation/ ...
As the duration of toluene
inhalation exposure increased, the LC50 in rats decreased from 26,700 ppm for 1
hr, to 12,200 ppm for 2-2.5 hr, to 8000 ppm for 4 hr.
Ecotoxicity Values:
LC50 FOR BLUEGILL WAS 17 MG/L/24 HR & 13
MG/L/96 HR (95% CONFIDENCE LIMIT 11-15 MG/L) @ 21-23 DEG C AFTER EXPOSURE TO TOLUENE.
/CONDITIONS OF BIOASSAY NOT SPECIFIED/
LC50 Palaemonetes pugio (grass shrimp) 9.5
mg/l/96 hr /Conditions of bioassay not specified/
LC50 Cancer magister (crab larvae stage I) 28
mg/l/96 hr /Conditions of bioassay not specified/
LC50 Crangon franciscorum (shrimp) 4.3 mg/l/96
hr /Conditions of bioassay not specified/
LC50 Pimephales promelas (fathead minnow)
56-34 mg/l/24-96 hr /Conditions of bioassay not specified/
LC50 Lebistes reticulatus (guppy) 63-59
mg/l/24-96 hr /Conditions of bioassay not specified/
LC50 Channel catfish 240 mg/l 96 hr
/Conditions of bioassay not specified/
LC50 Pimephales promelas (fathead minnow)
34.27 mg/l 96 hr (95% Confidence Limits= 22.83-45.86 mg/l) /Conditions of
bioassay not specified/
LC50 Carassius auratus (goldfish) 57.68 mg/l
96 hr (95% Confidence Limits= 48.87-68.75 mg/l) /Conditions of bioassay not
specified/
LC50 Lebistes reticulatus (guppy) 59.30 mg/l
96 hr (95% Confidence Limits= 50.87-70.34 mg/l) /Conditions of bioassay not
specified/
LC50 Daphnia magna, (water flea) 313 mg/l 48
hr /Conditions of bioassay not specified/
LC50 Nitocra spinipes (copepod) 24.2-74.2 mg/l
24 hr /Conditions of bioassay not specified/
LC50 Artemia salina (brine shrimp) 33 mg/l 24
hr /Conditions of bioassay not specified/
LC50 Morone saxatilis (striped bass) 7.3 mg/l
96 hr /Conditions of bioassay not specified/
LC50 Cyprinodon variegatus (sheepshead minnow)
277-485 mg/l 96 hr /Conditions of bioassay not specified/
LC50 Aedes aegypti-4th instar (mosquito
larvae) 22 mg/l /Conditions of bioassay not specified/
LC50 Calandra granaria (grain weevil) 210 mg/l
/in air/
LC50 Pimephales promelas (fathead minnows)
55-72 mg/l (embryos), 25-36 mg/l (1-day posthatch protolarvae), and 26-31 mg/l
(30-day-old minnows)/ 96 hour /Conditions of bioassay not specified/
EC50 Pimephales promelas (fathead minnow) 14.6
mg/l/96 hr (confidence limit 14.0 to 15.1 mg/l), flow-through bioassay with
measured concentrations, 24.7 deg C, dissolved oxygen 6.9 mg/l, hardness 45.4
mg/l calcium carbonate, alkalinity 43.4 mg/l calcium carbonate, and pH 7.89.
Effect: loss of equilibrium.
LC50 Pimephales promelas (fathead minnow) 36.2
mg/l/96 hr (confidence limit 29.4 to 44.6 mg/l), flow-through bioassay with
measured concentrations, 24.7 deg C, dissolved oxygen 6.9 mg/l, hardness 45.4
mg/l calcium carbonate, alkalinity 43.4 mg/l calcium carbonate, and pH 7.89.
TSCA Test Submissions:
Neurotoxicity was determined in groups of rats
(4 male and 4 female, strain not reported) exposed by inhalation to 0,100, or
1500 ppm toluene (purity not reported) 6 hrs/day, 5
days/week for periods up to 27 weeks. Histological sections of selected areas of
the brainstem were made for the upper medulla oblongata (including dorsal and
ventral cochlear and vestibular nuclei), lower metencephalon (including superior
olivary nuclei, trapezoid body and ventral cochlear nuclei), upper metencephalon
(including the lateral lemniscus, superior olivary nuclei, cochlear and
vestibular nuclei, and inferior colliculus) and the mesencephalon-diencephalon
junction (including the medial geniculate). The investigators reported that the
"vast majority" of sections from animals exposed to toluene
were indistinguishable from controls. Shrunken and darkly stained neurons were
observed in the corpus trapezoid of one animal exposed to 100 ppm and another
exposed to 1500 ppm toluene; these were present in only
one section and not in sufficient quantity to be considered a positive response
by the investigators. Statistical analysis of the results was not reported.
Chronic toxicity was evaluated in male and
female Sprague Dawley rats (15/sex/group) exposed to toluene
via inhalation at 0, 100 and 1500 ppm for 6 hrs/day, 5 days/week for 26 weeks.
There were significant increases in the hematocrit and hemoglobin levels in
females at 1500 ppm in the 13th week. There were significant differences in
females at week 26 in the following: decreased mean blood clotting time and
increased mean serum glutamic pyruvic transaminase at 100 ppm level, and
decreases in glucose levels at 1500 ppm. There were no significant differences
between treated and control animals in urinalysis.
Teratogenicity was evaluated in mated female
CRL:COBS CD (SD) BR rats (27/group) exposed to toluene
by inhalation at nominal concentrations of 0, 100 or 400 ppm on gestation days (GD)
6-15 for 6 hrs/day. The adult female rats were sacrificed on GD 20 and examined.
There were no significant differences observed between treated and control
animals in the following: maternal mortality, body weights, food consumption,
examination of tissues and organs at necropsy (except an insignificant number of
observations of mottled lungs in 4 high-dose group rats), pregnancy rate, live
litters, implantation sites, resorptions, litters with resorptions, dead pups,
litters with dead pups, live pups/implantation site, mean live litter size,
average pup weights, fetal sex ratio, examination of soft tissues of the head,
thoracic and visceral organs, and skeletal abnormalities.
The ability of toluene
to induce specific locus mutations at the TK locus in cultured L5178Y mouse
lymphoma cells (Mouse Lymphoma Mutagenesis Assay) was evaluated in the presence
and absence of mouse liver S9 metabolic activation. Based on preliminary
toxicity tests, both nonactivated and S9-activated cultures were treated with
0.30, 0.20, 0.15, 0.10, or 0.050 ul/ml produced a range of 7 - 78% total growth
for nonactivated cultures and from 60 - 138% total growth for S9-activated
cultures. None of the nonactivated or activated cultures produced mutant
frequencies significantly greater than the solvent (DMSO) controls.
The mutagenicity of toluene
was evaluated in Salmonella tester strains TA98, TA100, TA1535, TA1537 and
TA1538, and the yeast Saccharomyces cerevisiae tester strain D4, both in the
presence and absence of added metabolic activation by Aroclor-induced rat liver
S9 fraction. Based on preliminary bacterial toxicity determinations, toluene,
diluted with acetone, was tested for mutagenicity at concentrations up to 5.0 ul/plate
using both the plate and suspension assay methods. Toluene
did not cause a positive response in any of the bacterial or yeast tester
strains, either with or without metabolic activation.
The mutagenicity of toluene
was evaluated in a dominant lethal assay using three groups of male CD-1 mice
(12/group) receiving whole body exposures to nominal concentrations of test
material at 0, 100 or 400 ppm for 6 hrs/day, 5 days/week for 8 weeks. Following
exposure, each male was mated with two untreated females/week for two
consecutive weeks. Females were sacrificed 14 days after the midweek of mating.
There was no effect of treatment for all dosed male mice as indicated by
mortality, body weight and in-life physical observations. There were no
significant differences between treated and control females with respect to
fertility indices, average number of implants/pregnant female, average number of
dead implants/pregnant female, and proportions of female with one or more dead
implants.
The ability of toluene
to cause chromosome aberrations in the bone marrow cells of male Charles River
rats exposed by intraperitoneal injection at dose levels of 0, 0.025, 0.082 or
0.247 cc/kg (in DMSO solvent, 0.65 cc/rat/day), either once in an acute study
(15 rats/group) or once each day for 5 days in a subchronic study (5 rats/group)
was evaluated. Five rats/group in the acute study were sacrificed 6, 24 or 48
hrs following dosing and the rats in the subchronic study were sacrificed 6 hrs
after administration of the last dose. 50 cells/animal were scored for
chromosome aberrations. None of the cells from any of the treated animals
exhibited a significant increase in the frequency of chromosome aberrations.
The percutaneous absorption of toluene
was evaluated in six human volunteers. A glass ring having an area of 13cm(2)
was placed against the palm and 2ml of 14C-toluene was
applied. After one minute the ring was removed and adherent liquid allowed to
evaporate. All urine was collected and analyzed for radioactive content until
background levels of activity were approached. Toluene
absorption was very low, averaging .022ul/cm(2) for the six human subjects.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
Toluene is
extensively metabolized via oxidation to benzyl alcohol then to benzaldehyde by
alcohol dehydrogenase. Further oxidation then forms benzoic acid. Conjugation
with glycine produces the major metabolite, hippuric acid, which is excreted in
the urine. Benzyl glucuronide is formed in smaller amounts by conjugation with
glucuronic acid.
IN PRINTERS EXPOSED TO AIR CONTAINING TOLUENE
(AVG CONCN 23 PPM), URINARY EXCRETION OF O-CRESOL, WHICH IS NOT A NORMAL
CONSTITUENT OF URINE, WAS OBSERVED. APPARENTLY, TOLUENE
WAS OXIDIZED AT AROMATIC NUCLEUS FORMING CRESOLS, BESIDES HIPPURIC ACID.
In rats, approx 0.5%-1.1% of the dose is
converted to o-cresol and p-cresol and is excreted as glucuronide and sulfate
conjugates.
In mammalian species, acidic metabolites are
conjugated with glycine to form hippuric acid and phenylacetic acid. In humans,
the phenylacetic acid metabolite is also conjugated with glutamine to form
phenacetylglutamine.
The association between occupational toluene
exposure and blood and adipose tissue toluene
concentrations was examined. Breathing zone samples were monitored for toluene
in two Swedish rotogravure printing facilities. Sc adipose tissues were taken
from 37 workers after work on Thursday or Friday and analyzed for toluene.
Venous blood samples were taken from 11 workers after work on Friday and at
various times over the following weekend and assayed for toluene.
Blood and adipose tissue samples were obtained from 11 other workers immediately
after work and after 63 and 135 hours nonexposure and analyzed for toluene.
Blood samples were also taken from 21 unexposed workers and analyzed for toluene.
Attempts were made to fit the blood toluene data to
various pharmacokinetics models. Airborne toluene
concentrations in the printing factories ranged from 8 to 416 mg/cu m, median 75
mg/cu m. Blood toluene concentrations in the unexposed
workers were below the detection limit, 0.01 umole/l. Blood samples obtained
immediately after work contained 0.22 to 21.4 umole/l toluene.
Elimination of toluene from the blood could be
described by a three compartment model having median halftimes of 9 minutes, 2
hours, and 79 hours. Toluene was eliminated from
adipose tissue with a median halftime of 79 hours. Adipose tissue concentrations
were significantly associated with the workers' exposure to airborne toluene
during the previous week. Adipose tissue toluene
concentrations were significantly correlated with blood toluene
concentrations after 70 hours exposure. It was concluded that the prolonged
presence of toluene in the blood means that there is an
endogenous exposure from adipose tissue depots that continues long after
occupational exposure has ended.
Evidence has suggested that there is an ethnic
related difference in organic solvent metabolism in humans; analyses were thus
made to obtain evidence of strain differences in animals to assist in
consolidating the observation in workers. Female Donryu, Fischer, Sprague-Dawley,
and Wistar rats were exposed to toluene at dose levels
of 5, 45, 500, 2500, and 3500 ppm for 8 hours in a dynamic flow type exposure
system. Urine samples were collected for 24 hours from the start of exposure.
While the variation in free p-cresol excretion was wide among the rats of the
same strain exposed to toluene at the same
concentration, it was also noted that the four strains tested could be
classified into two groups depending on the free p-cresol levels at toluene
concentrations up to 500 ppm. No significant differences were noted between
Sprague-Dawley and Wistar strains nor between Donryu and Fischer strains at the
45 and 500 ppm levels. However, there were significant differences between these
two groups. At higher concentrations of 2500 and 3500 ppm, the increase in the
free p-cresol levels was remarkable only in Donryu rats, reaching the levels of
Sprague-Dawley and Wistar rats, while the level in Fischer rats remained
unchanged.
The mutual metabolic suppression between
benzene and toluene was studied. The subjects, 190 male
Chinese workers employed in shoe manufacturing, printing, audio equipment
manufacture, and automobile industries, were divided into four groups based on
occupational exposure: 65 were exposed to benzene, 35 to toluene,
55 to both compounds, and 35 served as comparisons. The arithmetic mean exposure
level of benzene was 31.9 and of toluene 44.7 ppm. The
mixture contained benzene at 17.9 +/29.3 and toluene at
20.5 +/25.8 ppm. The exposure levels were measured using individuals diffusive
samplers. The geometric mean levels of the metabolites, phenol, catechol,
hydroquinone, hippuric acid, and o-cresol, in unexposed workers were 6.9, 9.4,
4.8, 72.5, and 0.066 mg per liter, respectively. Values corrected for creatinine
and specific gravity were different from the values cited above. Multiple
correlation coefficients for benzene exposure versus its three metabolites were
for phenol, 0.740; for catechol, 0.629; and for hydroquinone, 0.726. Multiple
correlation coefficients for toluene and its two
metabolites were 0.649 for hippuric acid and 0.583 for o-cresol. The slopes of
regression lines for the exposure to benzene in the presence of toluene
were less than half of those obtained when the workers were exposed to benzene
alone; however, the regression lines for benzene in mixture versus catechol were
about 80% or higher than the lines observed with benzene as the sole pollutant.
The regression lines for toluene in the mixture and
excretion level of hippuric acid and o-cresol showed reduced metabolic
conversion compared to when exposure was limited to toluene
alone. It was concluded that simultaneous exposure to benzene and toluene
results in mutual suppression of metabolism yielding the urinary metabolites
phenol, hydroquinone, hippuric acid, and o-cresol.
Absorption, Distribution & Excretion:
TOLUENE VAPOR IS
READILY ABSORBED BY INHALATION AND THE LIQUID BY THE GI TRACT, BUT POORLY FROM
THE SKIN.
IN DOGS SUBJECTED TO INHALATION ... HIGHEST
CONCENTRATIONS WERE FOUND IN THE ADRENALS (20 UG/G), BRAIN (19 UG/G IN
CEREBELLUM & 18 UG/G IN CEREBRUM), AND BONE MARROW (18 UG/G).
ALTHOUGH SOME ABSORBED TOLUENE
MAY BE REEXHALED BY LUNG, MAJOR EXCRETORY PATHWAY IS RAPID OXIDATION OF TOLUENE
TO BENZOIC ACID, WHICH IS CONJUGATED WITH GLYCINE & EXCRETED AS HIPPURIC
ACID IN URINE. ... WITHIN REASONABLE LIMITS, EXCRETION OF HIPPURIC ACID IN URINE
IS PROPORTIONAL TO EXPOSURE. AN EXPOSURE OF 200 PPM OF TOLUENE
RESULTED IN EXCRETION OF 3.5 G HIPPURIC ACID PER LITER OF URINE (SPECIFIC
GRAVITY 1.016).
SIX SUBJECTS EXPOSED TO TOLUENE
IN INSPIRED AIR (50, 100, 150 PPM) SHOWED LITTLE DIFFERENCE IN RATE OF RESP
SOLVENT UPTAKE. NO SIMPLE RELATION EXISTED BETWEEN UPTAKE RATE & PERIPHERAL
VENOUS CONCN, INDICATING THAT NO CALCULATION COULD BE MADE FOR TOXIC DOSE OF
INNER ORGANS. DIFFERENCES IN RESP EXCRETION WAS EXPLAINED BY RESP MINUTE VOL IN
POST-EXPOSURE PERIOD, &, AFTER EXPOSURE AT REST, THE AMT OF BODY FAT.
FOLLOWING SINGLE IP ADMIN OF (14)C-LABELED TOLUENE
(290 UG/KG) TO MICE, HIGHEST LEVEL OF RADIOACTIVITY WAS FOUND IN ADIPOSE TISSUE,
FOLLOWED IN DESCENDING ORDER BY KIDNEY, LIVER & LUNG. LOWEST ACTIVITY WAS IN
BRAIN TISSUE & BLOOD/BRAIN RATIO WAS ABOUT 0.4.
The blood/gas partition coefficient ranges
from 12.4 to 15.6.
At equilibrium, the avg toluene
concn per liter of blood is 2.4 mg for each 100 ppm toluene
in the envir air.
... Whole body autoradiography has been
modified and applied to distribution studies of ... toluene.
...
The urinary excretion of hippuric acid and
o-cresol in humans was measured after a 7 hr exposure to toluene
at a constant concn of 100 ppm but with a time-weighted avg of 100 ppm. In study
A, 4 men were exposed to clean air and to constant and varying concns of toluene
in combination with rest and with 100 W exercise for 140 min exercise increased
the end-exposure excretion rate of hippuric acid and o-cresol by 47 and 114%,
respectively. After exposure, all excess hippuric acid was excreted within 4 hr,
while o-cresol was eliminated with a half-life of approx 3 hr. Alveolar air
concn of toluene was 21-31 ppm during constant exposure
and 13-57 ppm during varying exposure, but no difference in mean alveolar toluene
concn or in metabolite excretion was seen between the exposure schedules. In
study B, 32 men and 39 women aged between 31 and 50 yr were exposed once to
either clean air or ... or varying concns of toluene.
The background excretion rate of hippuric acid was 0.97 mg/min (1.25 g/g
creatinine) and rose to 3.74 mg/min (3.90 g/g creatinine) during the last 3 hr
of exposure to 100 pmm toluene. The corresponding
figures for o-cresol were 0.05 ug/min (0.08 mg/g creatinine ), and 2.04 ug/min
(2.05 mg/g creatinine). The individual creatinine excretion rate was
considerably influenced by sex, body wt, and smoking habits, thus influencing
the metabolite concn standardized in relation to creatinine. Thus, both
metabolites are estimates of toluene exposure; o-cresol
is more specific than hippuric acid, but the individual variation in excretion
of both metabolites is large, and when implementing either of them as biological
exposure indexes, the influence of sex, body size, age as well as consumption of
tobacco and alcohol has to be considered.
The distribution of radioactivity in pregnant
mice was registered at different time intervals (0-24 hr) after a 10 min period
of inhalation of toluene. ... Autoradiographic and liq
scintillation methods were used to make possible the distinction between
volatile, water sol, and firmly tissue bound radioactivity. Toluene
reached high concns immediately after inhalation in lipid rich tissues (brain
and fat) and well perfused organs (liver and kidney) but were rapidly eliminated
resulting in low concns at 1 hr in all maternal tissues, except fat. Metabolites
reached peak levels around 30 min to 1 hr after inhalation, but were also
relatively rapidly eliminated. ... One exception was the very strong
accumulation of water sol metabolites at 4 and 24 hr in the nasal mucosa and
olfactory bulb after inhalation of toluene. Volatile
radioactivity was observed in the placenta and fetuses immediately and up to 1
hr after inhalation of solvent at all stages of gestation. The fetal levels
were, however, much lower than in maternal tissues. In early gestation, an even
distribution pattern was observed, while the fetal liver reached a higher concn
than other fetal tissues in late gestation. In similarity with maternal tissues,
fetal tissues reached the highest levels of metabolites 30 min to 1 hr after
inhalation. A retention in uterine fluid was seen at 4 hr. Otherwise no
retention of metabolites was observed in the fetoplacental unit. No firmly
tissue bound metabolites of the studied solvents were observed in the fetal
tissues in late gestation, indicating no fetal capacity for formation of
reactive metabolites.
A study was instituted to determine whether
gavage dosing and inhalation exposure resulted in similar blood levels of toluene.
Groups of male Sprague-Dawley rats were dosed with toluene
either by gavage with 0.10, 0.25, 0.50, or 1.0 mg/kg/body weight or through
exposure to atmospheres containing 200 to 1000 ppm toluene.
Blood samples were taken at 0.5, 1.0, 2.0, 4.0, 6.0, and 24.0 hours following
dosing. Steady state blood concentrations were reached for both inhaled doses
within 30 minutes of the exposure. After 6 hours the steady state toluene
blood concentrations for the 200 and 1000 ppm dose levels were 2.89 and 37.23
ppm, respectively. For the oral doses, the peak blood toluene
concentration increased with increasing dosage. Blood profiles from higher oral
doses more closely approximated the steady state inhalation blood profiles. At
24 hours following dosing, blood toluene levels from
all doses by either route were below detectable levels, suggesting minimal carry
over of toluene concentrations from one day to the
next. An equation was derived which will allow the gavage dose of toluene
to be made equivalent to an inhalation dose. Based on results of other studies,
it was suggested that blood toluene levels following sc
injection more closely resemble those obtained following inhalation than do
blood levels after gavage. However, it is possible to obtain blood
concentrations of toluene similar to those generated by
a 6 hour inhalation exposure to 1000 ppm through gavage dosing.
An investigation was carried out to quantitate
the effect of pulmonary ventilation on uptake and biological concentrations of
six organic solvents. Tested solvents were acetone, styrene, toluene,
xylenes, methylchloroform, and tetrachloroethylene. Lung uptake and urinary
concentration (Cu) were measured in 15 volunteers, 24 to 52 years old, exposed
in a chamber for 2 or 4 hours at rest, 2 hours with three alternations of light
exercise, 1 hour of light exercise, or 30 minutes or more strenuous exercise.
Environmental levels and urinary concentration were measured in 528
occupationally exposed workers before and after 4 hours of work at a light task
(pulmonary ventilation 12 to 18 liters per minute). For volunteers, uptake and
urinary concentration values were significantly correlated. Environmental levels
and urinary concentration showed a close relationship for occupational exposure.
Biological equivalent exposure limits corresponding to threshold limit value (TLV)
time weighted averages were derived from urinary concentration values. For
acetone, styrene, and xylenes, uptake for a given time and exposure level was
dependent only on ventilation. The toluene retention
index was slightly lower for exercise than for rest, and uptake was ventilation
dependent during rest and ventilation and retention index dependent during
exercise. Retention indices decreased with increasing ventilation at rest and
during exercise for tetrachloroethylene and methylchloroform. Their urinary
concentration values were ventilation and retention index dependent.
Methylchloroform uptake was higher during light versus heavy exercise. It was
concluded that work load profoundly affects the absorbed amount of chemical and
should be a factor in implementation of biological exposure indices and TLVs.
Animal studies indicate that toluene
readily crosses the placenta.
When dogs were exposed to 0.4-0.6 ug/ml toluene
vapor, 91-94% was taken up in the lungs. Absorption was complete when toluene
was given orally to dogs; the blood level in rats increased more slowly after
oral administration than after inhalation. Absorption through the skin of mice
in vivo was 4.50 ug/sq cm per hour. Toluene penetrated
rat skin excised three days after clipping and depilation with cream at a rate
one-tenth that of benzene and ten times that of ortho-xylene.
Toluene levels in
brain and blood were linearly related to toluene levels
in inhaled air after rats were exposed to 50, 100, 500, or 1000 ppm (189, 377,
1885, or 3770 mg/cu m) toluene for 3 hr.
When rabbits were given a single oral dose of
350 mg/kg bw toluene, 19% was exhaled unchanged within
12 hr.
Pregnant C57B1 mice were exposed by inhalation
to 14C-toluene (theoretical concentration, 2000 ppm
(7540 mg/cu m)) for 10 min on days 11, 14 or 17 of gestation, and distribution
of the label was determined 0, 0.5, 1, 4 and 24 hr after exposure. The label
quickly entered the embryo, but uptake was low relative to that in maternal
tissues. All fetal activity was extractable, indicating that no firmly bound
metabolite was present.
In humans, up to 75% of inhaled toluene
is metabolized to hippuric acid and excreted in the urine within 12 hr of
exposure. The remainder of the toluene is mainly
excreted unchanged with a small percent being excreted as a sulfate or
glucuronide of cresol.
The uptake of toluene
in the blood is doubled during physical activity compared to the uptake at rest.
In nude mice exposure to 300, 1000, or 3000
ppm toluene under conditions where there was no
respiratory intake of toluene, led to a dose-related
and duration-related increase in whole body toluene
levels. The calculated skin absorption coefficient was 1.24 cm/hr. The skin
absorption rate for the 300 ppm concentration was 0.0009 mg/sq cm/hr; for the
1000 ppm concentration , it was 0.0046 mg/sq cm/hr; and for the 3000 ppm
concentration, it was 0.0144 mg/sq cm/hr.
In humans, the toluene
is distributed between the plasma and red blood cells at approximately a 1:1
ratio according to in vitro data; in rats, the ratio is 1:2 based on in vivo
data.
In one human who died 30 min after ingestion
of 625 mg/kg toluene, the liver was found to have the
highest concentration of toluene (133.5 ug/g) followed
by the pancreas (88.2 ug/g), brain (85.3 ug/g), heart (62.6 ug/g), blood (12.2
ug/g), body fat (12.2 ug/g), and cerebrospinal fluid (11.1 ug/g).
Biological Half-Life:
0.083 days (Inhaled as environmental air)
Mechanism of Action:
... Toluene at low
concn /less than 100 ppm/ may produce disturbances in dopaminergic mechanisms of
the basal ganglia probably leading to functional changes in sensory-motor
integration. ...
Exposure to toluene
causes both reversible and irreversible changes in the central nervous system.
The effects of toluene inhalation on some specific
enzymes and glutamate and GABA receptor binding in defined parts of the rat
brain were studied following several exposure schemes. The activities of the
transmitter synthesizing enzymes glutamic acid decarboxylase (GAD), choline
acetyltransferase (ChAT) and aromatic amino-acid decarboxylase (AAD) were used
as markers for permanent loss of neuronal activity. Catecholaminergic neurons
showed a 50% reduction in the brain stem after 4 weeks exposure to 250 and 1000
ppm toluene. Following 500 ppm of toluene,
16 hr/day for 3 months, a general increase in the activities was seen. This is
most probably due to a reduction in total protein content, to which the
activities were related. The neurotransmitters glutamate and GABA had their
specific receptor binding increased in most of the brain areas studied, but
decreased in some areas. The glial enzyme, glutamine synthetase, has its
activity increased in the cerebellar hemisphere following 4 weeks exposure to
1000 ppm. This suggests that glial cells in the area may have proliferated, a
frequent phenomenon following CNS damage.
The effect of styrene, toluene,
ethylbenzene, alpha-methylstyrene, and butylbenzene on oxidative phosphorylation
was studied using rat liver mitochondrial preparations. Rat liver mitochondria
were prepared from male white Wistar rats and assessed for respiration rate,
oxygen uptake, glutamate oxidation, succinate oxidation, ATPase activity, and
proton permeability in the presence and absence of the alkyl benzene
derivatives. Inclusion of the alkyl benzene derivatives in the incubation medium
produced an initial acceleration of oxygen consumption followed by an inhibition
of glutamate oxidation, and the stimulatory effect paralleled the aliphatic
chain length. Glutamate oxidation was also inhibited by styrene, ethylbenzene,
and alpha-methylstyrene but not by butylbenzene or toluene
in 2,4-dinitrophenol uncoupled mitochondria. Styrene and the aliphatic benzene
derivative stimulated succinate oxidation in rat liver mitochondria without
effect on 2,4-dinitrophenol stimulated succinate oxidation. Similar stimulatory
effects on ATPase activity were observed with maximal stimulation occurring at
the same relative concentrations producing maximal succinate oxidation. ATPase
stimulation required magnesium, was oligomycin sensitive, and showed an inverse
relation to the hydrophobicity of the compounds tested. The inclusion of styrene
in the incubation medium markedly increased the rate of passive entry of protons
into rat liver mitochondria in a manner comparable to 2,4-dinitrophenol. It was
concluded that styrene and other monosubstituted benzene derivatives act as
mitochondrial uncoupling agents.
Interactions:
IP LD50 OF TOLUENE
FOR MALE MICE WAS 1.15 G/KG. PRETREATMENT WITH PHENOBARBITAL, PRODUCED MARKED
DECR IN SLEEP INDUCED BY TEST DOSE (0.96 G/KG IP) OF TOLUENE.
PRETREATMENT WITH HEPATIC ENZYME INHIBITORS SUCH AS CARBON TETRACHLORIDE,
2-DIETHYLAMINOETHYL-2,2-DIPHENYLATE HYDROCHLORIDE, PYRAZOLE & CYANAMIDE
PRODUCED INCR IN SLEEP & DEATH ASSOC WITH PROLONGATION OF SLEEPING TIME.
TOLUENE WITH ASPHALT
FUMES OR CHLORINATED HYDROCARBONS, SUCH AS TRICHLOROETHYLENE &
TETRACHLOROETHENE, CAUSES DEPRESSION OF HYDROXYLATION & URINARY CONJUGATE
EXCRETIONS. ... COMBINED EXPOSURE TO TOLUENE, XYLENE,
FORMALDEHYDE, & ANILINE DYES DECR GRANULOCYTIC PHOSPHATASE ACTIVITY.
CONVERSELY, HYDROGEN PEROXIDE ADMIN TO RATS INCR THE BLOOD PEROXIDE ACTIVITY
& INCR THE TOLERANCE TO TOLUENE, AS DID
PHENOBARBITAL IN SPECIFIC QUANTITIES.
SPRAGUE-DAWLEY RATS WERE EXPOSED BY INHALATION
TO TOLUENE (500, 1500, & 3000 PPM) FOR 3 DAYS. TOLUENE
INCR CONCN OF LIVER MICROSOMAL CYTOCHROME P-450. A DOSE-DEPENDENT INCR IN THE IN
VITRO LIVER MICROSOMAL FORMATION OF SEVERAL METABOLITES OF BIPHENYL &
BENZO(A)PYRENE WAS OBSERVED FOR TOLUENE. TOLUENE
MODIFIED THE METABOLISM AND TOXICITY OF OTHER ENVIRONMENTAL CONTAMINANTS.
Perchloroethylene enhances toxicity of toluene
admin orally in rats.
Toluene and
trichloroethylene seem to exhibit competitive inhibition.
CFY rats ... on day 12 of pregnancy ... dams
were given: 0, 125, 250, 500 and 3,600 mg/cu m ... and 250 mg/kg acetylsalicylic
acid by gavage; two subgroups ... treated with 250 mg/kg acetylsalicylic acid in
combination with 3,600 mg/cu m toluene inhalation were
given 0, 2.5, or 5 gm/kg glycine 2 hours before the acetylsalicylic acid dose.
... Toluene was found to potentiate the toxic effect of
acetylsalicylic acid and to increase both maternal and embryonic toxicity ...
increasing acetylsalicylic acid embryotoxicity caused by toluene
can be warded off by glycine administration.
The metabolic interaction of toluene
and ethanol was studied in male rabbits having received ethanol (26.0 mmol/kg po),
toluene (5.4 mmol/kg po) or both. Compared with ethanol
alone, toluene given 2 hr after ethanol caused a
significantly higher and more prolonged concentration of blood alcohol. A
similar trend of blood alcohol was observed at the later stage with toluene
given prior to ethanol. On the other hand, with simultaneous doses of the two
substances, the blood toluene concentration was higher
for the first 15-30 min than the ethanol control and the urinary excretion of
hippuric acid, a main metabolite of toluene, was
markedly decreased for the first 2 hr. The blood ethanol in this group, on the
contrary, was reduced until 1 hr after administration. These results indicate
that toluene and ethanol act reciprocally as
competitive inhibitors in their metabolism after single administrations.
In an experimental human study, the effect of toluene
and ethanol (alone or in combination) on psychophysiologic functions was studied
in 12 men (22-44 yr of age). Each subject served as his own control. Subjects
were exposed to toluene by inhalation at a
concentration of 300 mg toluene/cu m air for 4.5 hr.
Ethanol was ingested at a dose equivalent to 15 mmol ethanol/kg body weight. Toluene
had no significant effect on the 4 performance tests. A significant but weak
depression of heart rate was observed during sleep latency tests (1-2.5
beats/min, 0.001 <p< 0.01). There was a significant increase in reporting
of headache (p< 0.05) and in reporting for all symptoms (nausea, headache,
irritation) combined (p< 0.05). No interaction between ethanol and toluene
was observed.
Male Sprague-Dawley rats were used to study
the renal toxicity potential of subchronic exposure to non-toxic doses of a
combination of styrene and toluene. Four groups (n= 6)
of rats were injected ip with: (1) 4 mmol styrene 2 times/day at 4 hr intervals;
(2) 10 mmol toluene/kg once a day; (3) 4 mmol
styrene/kg 2 times/day plus 10 mmol toluene/kg
once/day; (4) All treatments were given 5 days/wk for 4 consecutive wk. By the
fourth wk, there was a significant increase (p< 0.05) in urinary excretion of
gamma-glutamyl transpeptidase, protein, and glucose by the group receiving
combined treatment versus those receiving treatment with either chemical alone.
There was an increase in excretion of hippuric acid in the mixture treatment
group, but no increase in mandelic and phenylglyoxylic acids or thioethers.
Blood urinary nitrogen was not modified by the individual chemicals or the
mixture. Electron microscopic examination of the kidney showed an increase of
single membrane vacuoles in the proximal convoluted tubules of rats treated with
a mixture of chemicals, but not with toluene or styrene
alone.
... Toluene has been
shown to be a competitive inhibitor of the metabolism of benzene. This
competitive interaction alleviates the metabolite-mediated toxicity of benzene
...
Xenobiotic competitors for the same metabolic
route, such as benzene and xylene, would ... have an impact on toluene
metabolism.
... A single alcoholic drink has a very
strong, acute inhibitory effect on the hepatic elimination of toluene.
The aim of this study was to examine if the
drug chlorzoxazone has any influence on the toxicokinetics of acetone and toluene.
Chlorzoxazone is mainly metabolized by the same enzyme (Cytochrome P450 2E1) as
ethanol and many other organic solvents. Ten male volunteers were exposed to
solvent vapor (2 hr, 50 watt) in an exposure chamber. Each subject was exposed
to acetone only (250 ppm), acetone + chlorzoxazone, toluene
(50 ppm) only, toluene + chlorzoxazone, and
chlorzoxazone only. Chlorzoxazone (500 mg) was taken as two tablets 1 h prior to
solvent exposure. Samples of blood, urine and exhaled air were collected before,
during and until 20 h post exposure. The time-concentration curves of acetone
and toluene in blood were fitted to one- and
four-compartment toxicokinetic models, respectively. Except for a delayed
excretion of hippuric acid in urine, no effects on the toluene
toxicokinetics were seen after chlorzoxazone treatment. Small increases in
chlorzoxazone plasma levels were seen after exposure compared to chlorzoxazone
alone. These interactions, although statistically significant, seem to be small
compared to the interindividual variability on metabolism and toxicokinetics.
Pharmacology:
Interactions:
IP LD50 OF TOLUENE
FOR MALE MICE WAS 1.15 G/KG. PRETREATMENT WITH PHENOBARBITAL, PRODUCED MARKED
DECR IN SLEEP INDUCED BY TEST DOSE (0.96 G/KG IP) OF TOLUENE.
PRETREATMENT WITH HEPATIC ENZYME INHIBITORS SUCH AS CARBON TETRACHLORIDE,
2-DIETHYLAMINOETHYL-2,2-DIPHENYLATE HYDROCHLORIDE, PYRAZOLE & CYANAMIDE
PRODUCED INCR IN SLEEP & DEATH ASSOC WITH PROLONGATION OF SLEEPING TIME.
TOLUENE WITH ASPHALT
FUMES OR CHLORINATED HYDROCARBONS, SUCH AS TRICHLOROETHYLENE &
TETRACHLOROETHENE, CAUSES DEPRESSION OF HYDROXYLATION & URINARY CONJUGATE
EXCRETIONS. ... COMBINED EXPOSURE TO TOLUENE, XYLENE,
FORMALDEHYDE, & ANILINE DYES DECR GRANULOCYTIC PHOSPHATASE ACTIVITY.
CONVERSELY, HYDROGEN PEROXIDE ADMIN TO RATS INCR THE BLOOD PEROXIDE ACTIVITY
& INCR THE TOLERANCE TO TOLUENE, AS DID
PHENOBARBITAL IN SPECIFIC QUANTITIES.
SPRAGUE-DAWLEY RATS WERE EXPOSED BY INHALATION
TO TOLUENE (500, 1500, & 3000 PPM) FOR 3 DAYS. TOLUENE
INCR CONCN OF LIVER MICROSOMAL CYTOCHROME P-450. A DOSE-DEPENDENT INCR IN THE IN
VITRO LIVER MICROSOMAL FORMATION OF SEVERAL METABOLITES OF BIPHENYL &
BENZO(A)PYRENE WAS OBSERVED FOR TOLUENE. TOLUENE
MODIFIED THE METABOLISM AND TOXICITY OF OTHER ENVIRONMENTAL CONTAMINANTS.
Perchloroethylene enhances toxicity of toluene
admin orally in rats.
Toluene and
trichloroethylene seem to exhibit competitive inhibition.
CFY rats ... on day 12 of pregnancy ... dams
were given: 0, 125, 250, 500 and 3,600 mg/cu m ... and 250 mg/kg acetylsalicylic
acid by gavage; two subgroups ... treated with 250 mg/kg acetylsalicylic acid in
combination with 3,600 mg/cu m toluene inhalation were
given 0, 2.5, or 5 gm/kg glycine 2 hours before the acetylsalicylic acid dose.
... Toluene was found to potentiate the toxic effect of
acetylsalicylic acid and to increase both maternal and embryonic toxicity ...
increasing acetylsalicylic acid embryotoxicity caused by toluene
can be warded off by glycine administration.
The metabolic interaction of toluene
and ethanol was studied in male rabbits having received ethanol (26.0 mmol/kg po),
toluene (5.4 mmol/kg po) or both. Compared with ethanol
alone, toluene given 2 hr after ethanol caused a
significantly higher and more prolonged concentration of blood alcohol. A
similar trend of blood alcohol was observed at the later stage with toluene
given prior to ethanol. On the other hand, with simultaneous doses of the two
substances, the blood toluene concentration was higher
for the first 15-30 min than the ethanol control and the urinary excretion of
hippuric acid, a main metabolite of toluene, was
markedly decreased for the first 2 hr. The blood ethanol in this group, on the
contrary, was reduced until 1 hr after administration. These results indicate
that toluene and ethanol act reciprocally as
competitive inhibitors in their metabolism after single administrations.
In an experimental human study, the effect of toluene
and ethanol (alone or in combination) on psychophysiologic functions was studied
in 12 men (22-44 yr of age). Each subject served as his own control. Subjects
were exposed to toluene by inhalation at a
concentration of 300 mg toluene/cu m air for 4.5 hr.
Ethanol was ingested at a dose equivalent to 15 mmol ethanol/kg body weight. Toluene
had no significant effect on the 4 performance tests. A significant but weak
depression of heart rate was observed during sleep latency tests (1-2.5
beats/min, 0.001 <p< 0.01). There was a significant increase in reporting
of headache (p< 0.05) and in reporting for all symptoms (nausea, headache,
irritation) combined (p< 0.05). No interaction between ethanol and toluene
was observed.
Male Sprague-Dawley rats were used to study
the renal toxicity potential of subchronic exposure to non-toxic doses of a
combination of styrene and toluene. Four groups (n= 6)
of rats were injected ip with: (1) 4 mmol styrene 2 times/day at 4 hr intervals;
(2) 10 mmol toluene/kg once a day; (3) 4 mmol
styrene/kg 2 times/day plus 10 mmol toluene/kg
once/day; (4) All treatments were given 5 days/wk for 4 consecutive wk. By the
fourth wk, there was a significant increase (p< 0.05) in urinary excretion of
gamma-glutamyl transpeptidase, protein, and glucose by the group receiving
combined treatment versus those receiving treatment with either chemical alone.
There was an increase in excretion of hippuric acid in the mixture treatment
group, but no increase in mandelic and phenylglyoxylic acids or thioethers.
Blood urinary nitrogen was not modified by the individual chemicals or the
mixture. Electron microscopic examination of the kidney showed an increase of
single membrane vacuoles in the proximal convoluted tubules of rats treated with
a mixture of chemicals, but not with toluene or styrene
alone.
... Toluene has been
shown to be a competitive inhibitor of the metabolism of benzene. This
competitive interaction alleviates the metabolite-mediated toxicity of benzene
...
Xenobiotic competitors for the same metabolic
route, such as benzene and xylene, would ... have an impact on toluene
metabolism.
... A single alcoholic drink has a very
strong, acute inhibitory effect on the hepatic elimination of toluene.
The aim of this study was to examine if the
drug chlorzoxazone has any influence on the toxicokinetics of acetone and toluene.
Chlorzoxazone is mainly metabolized by the same enzyme (Cytochrome P450 2E1) as
ethanol and many other organic solvents. Ten male volunteers were exposed to
solvent vapor (2 hr, 50 watt) in an exposure chamber. Each subject was exposed
to acetone only (250 ppm), acetone + chlorzoxazone, toluene
(50 ppm) only, toluene + chlorzoxazone, and
chlorzoxazone only. Chlorzoxazone (500 mg) was taken as two tablets 1 h prior to
solvent exposure. Samples of blood, urine and exhaled air were collected before,
during and until 20 h post exposure. The time-concentration curves of acetone
and toluene in blood were fitted to one- and
four-compartment toxicokinetic models, respectively. Except for a delayed
excretion of hippuric acid in urine, no effects on the toluene
toxicokinetics were seen after chlorzoxazone treatment. Small increases in
chlorzoxazone plasma levels were seen after exposure compared to chlorzoxazone
alone. These interactions, although statistically significant, seem to be small
compared to the interindividual variability on metabolism and toxicokinetics.
Minimum Fatal Dose Level:
Ingestion of approximately 60 ml (625 mg/kg)
of toluene proved fatal for a while male mental
patient.
Environmental Fate & Exposure:
Environmental Fate/Exposure Summary:
Toluene is released
into the atmosphere principally from the volatilization of petroleum fuels and toluene-based
solvents and thinners and from motor vehicle exhaust. Toluene's
production and use as an intermediate in the production of benzoic acid,
benzaldehyde, benzene, explosives, dyes and many other organic compounds may
also result in its release to the environment through various waste streams. Toluene
has been detected in emissions from volcanos, forest fires and crude oil. If
released to air, a vapor pressure of 28.4 mm Hg at 25 deg C indicates toluene
will exist solely as a vapor in the ambient atmosphere. Vapor-phase toluene
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 3
days. Toluene may also be degraded in the atmosphere by
reaction with nitrate radicals and ozone molecules, but these reactions are too
slow to be environmentally important. If released to soil, toluene
is expected to have high to moderate mobility based upon Koc values in the range
of 37-178. Volatilization from moist soil surfaces is expected to be an
important fate process based upon a Henry's Law constant of 6.64X10-3 atm-cu
m/mole. Toluene may volatilize from dry soil surfaces
based upon its vapor pressure. Biodegradation is expected to occur rapidly in
soil surfaces, with half-lives in the range of several hours to 71 days. If
released into water, toluene is not expected to adsorb
to suspended solids and sediment based upon a Koc of 166 measured in lake
sediment. Biodegradation is expected to occur rapidly in water, with reported
half-lives of 4 and 56 days in aerobic and anaerobic water, respectively.
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 1 hour and 4 days, respectively.
Measured BCF values of 13 and 90 in fish suggest bioconcentration in aquatic
organisms is low to moderate. Hydrolysis is not expected to be an important
environmental fate process for toluene due to lack of
hydrolyzable functional groups. Exposure to toluene may
occur occupationally during its production or subsequent use, particularly as a
solvent or in gasoline, via dermal and respiratory routes. The main route of
exposure for the general population will be through inhalation from contaminated
air and handling of gasoline as well as ingestion of contaminated drinking water
and food, and exposure to some consumer products. (SRC)
Probable Routes of Human Exposure:
NIOSH (NOES Survey 1981-1983) has
statistically estimated that 1,625,598 workers (288,299 of these are female) are
potentially exposed to toluene in the US(1).
Occupational exposure to toluene may occur through
inhalation and dermal contact with this compound at workplaces where toluene
is produced or used(SRC). The general population may be exposed to toluene
via inhalation of ambient air, ingestion of food and drinking water, handling of
gasoline, and exposure to some consumer products where toluene
is used as a solvent(SRC).
Toluene was detected
in hairdresser salons in Norway at concns of 0.04-0.11 mg/cu m(1). The time
weighted average (TWA) of toluene in the workplace air
of a municipal waste composting facility was reported as 188,000 ug/cu m(2). In
a 1989 Danish survey on chemical exposures(3), the number of worker exposure
events for toluene were documented: manufacturing of
metals, 420; manufacturing of metal fabricated products 64,000; electrical
machinery and apparatus, 1,500; manufacture of transport equipment 2,700;
painters and carpenters 15,000; construction workers, 5,400; publishing and
printing, 6,300; wholesale trades, 5,000; textile and leather manufacturing,
4,400; wood and furniture manufacturing, 5,900; manufacture of chemicals, 8,700;
manufacture of paints and petroleum, 1,400; manufacture of non-metallic mineral
products, 2,300; manufacture of optical instruments, 2,500 manufacture of
plastic and boat building, 1,100; sewage and refuse disposal, 99; agriculture
and forestry, 11,000; health services, 2,600. The total number of work related
exposure events was 140,000(3). Toluene was detected in
the workplace air of glass fiber manufacturing plants and high temperature
sealing component and clutch lining plants at a mean concn of 65 ppm(4).
Body Burden:
Toluene was
identified, not quantified, in 8 samples of mothers' milk from 4 urban areas(1).
Toluene was detected in 250 of 250 specimens of human
blood at concns of 0.2-38 ppb (1.5 ppb avg)(2). Toluene
was detected in 91% of the samples of the National Human Adipose Tissue Survey
at a max concn of 250 ppb(3). Toluene was identified,
not quantified, in expired breath of people at service stations during
fueling(4). The mean concn of toluene in the blood of
non-occupationally exposed individuals in the US was 0.52 ppb(5). The avg concn
of toluene in the blood and urine of workers in glass
fiber and clutch lining plants were 911 ug/l and 2.9 mg/l, respectively(6).
Average Daily Intake:
AIR INTAKE (assume median concn 11 ppb(1)) 843
ug; WATER INTAKE (assume 2 ppb(2)) 4 ug; FOOD INTAKE - insufficient data.
Natural Pollution Sources:
Toluene occurs in
nature in ... natural gas deposits ...
Toluene has been
detected in emissions from volcanos, forest fires and crude oil(1).
Artificial Pollution Sources:
Toluene is a major
constituent (20-60 ug/cigarette) of the gas phase of the mainstream smoke of
unfiltered cigarettes. /From table/
Toluene is released
into the atmosphere principally from the volatilization of petroleum fuels and toluene-based
solvents and thinners and from motor vehicle exhaust(1,2). Toluene's
production and use as an intermediate in the production of benzoic acid,
benzaldehyde, explosives, dyes and many other organic compounds(3) may also
result in its release to the environment through various waste streams(SRC).
Environmental Fate:
TERRESTRIAL FATE: Based on a classification
scheme(1), Koc values of 37-178 measured in soil(2,3), indicates that toluene
is expected to have high to moderate mobility in soil(SRC). Volatilization of toluene
from moist soil surfaces is expected to be an important fate process(SRC) given
a Henry's Law constant of 6.64X10-3 atm-cu m/mole(4). Toluene
may volatilize from dry soil surfaces based on a vapor pressure of 28.4 mm Hg at
25 deg C(5). Complete biodegradation of toluene was
observed in lab microcosm tests during a 40 hour incubation period using soils
previously exposed to toluene(6). The biodegradation
half-life in various soils was reported as several hours to 71 days(7).
AQUATIC FATE: Based on a classification
scheme(1), a Koc value of 166 measured in lake sediment(2) indicates that toluene
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
6.64X10-3 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 1 hour
and 4 days, respectively(SRC). According to a classification scheme(5), BCF
values of 13(6) and 90(7) measured in fish, suggest bioconcentration in aquatic
organisms is low to moderate. The half-life of toluene
in aerobic and anaerobic water was reported as 4 and 56 days, respectively(8).
ATMOSPHERIC FATE: According to a model of
gas/particle partitioning of semivolatile organic compounds in the
atmosphere(1), toluene, which has a vapor pressure of
28.4 mm Hg at 25 deg C(2), is expected to exist solely as a vapor in the ambient
atmosphere. Vapor-phase toluene is degraded in the
atmosphere by reaction with photochemically-produced hydroxyl radicals, nitrate
radicals and ozone molecules(SRC). The half-life for the reaction with hydroxyl
radicals is estimated to be 3 days(SRC), calculated from its rate constant of
5.96X10-12 cu cm/molecule-sec at 25 deg C(3). The half-life for the nighttime
reaction with nitrate radicals is estimated as 491 days(SRC) calculated from its
rate constant of 6.8X10-17 cu cm/molecule-sec at 25 deg C(3). The half-life for
the reaction with ozone is estimated as 27,950 days(SRC) calculated from its
rate constant of 4.1X10-22 cu cm/molecule-sec at 25 deg C(3).
Environmental Biodegradation:
Toluene is readily
degradable in a variety of standard biodegradability tests using sewage seed or
sludge inoculums(1-7). Degradation has been observed in several die-away tests
using seawater or estuarine water(9-12). The degradation rate is much faster in
systems which have been contaminated by oil(9,10). Complete degradation has been
observed in 4 days and 22 days in a marine mesocosm with summer and spring
conditions, respectively(12), and 10 days in a 1% gas oil mixture in a North Sea
coast water inoculum(8). A 90 day half-life in uncontaminated estuarine water
was reduced to 30 days in oil-polluted water(10). The half-life in water
collected near Port Valdez, Alaska was 12 days(9). 1.5 mM and 3 mM Ring-labeled toluene
added to a methanogenic inoculum originally enriched from sewage sludge and
incubated at 35 deg C for 60 days resulted in 3.6 and 4.5% 14-C final activity
respectively(13).
Toluene completely
degraded in groundwater in 8 days including a lag of 3-4 days while microbial
populations became acclimated(1). Other investigators found that only 1-2% of toluene
degraded in the subsurface environment(2) and >90% degraded in 4 weeks in
soil cores at various depths both above and below the water table(3,5).
Microbial attack proceeds via immediate hydroxylation of the benzene ring
followed by ring-cleavage or oxidation of the side chain followed by
hydroxylation and ring-cleavage(4).
Complete biodegradation of toluene
was observed in lab microcosm tests during a 40 hour incubation period using
soils previously exposed to toluene(1). Toluene
was rapidly degraded in soil column experiments using acclimated soil at a rate
of 8-35 mg/kg-day, and the rate followed zero-order kinetics(2). First-order
degradation rate constants of 0.0005 to 0.0063 day-1 were measured for toluene
in a gasoline-contaminated aquifer zone(3). These rate constants correspond to
half-lives of 100-1,386 days(3). A first-order biodegradation rate constant of
0.045 day-1 was reported for toluene in an anaerobic
petroleum contaminated aquifer, corresponding to a biodegradation half-life of
15 days(4). Toluene was rapidly biodegraded by
indigenous mixed cultures in sandy aquifer material and pure cultures isolated
from the aquifer(5). The zero-order rate constant for the aquifer material was
23 mg/l-day and had a lag period of 2 days(5). The half-life of toluene
in aerobic and anaerobic water was reported as 4 and 56 days, respectively(6).
The biodegradation half-life in various soils was reported as several hours to
71 days(7).
Environmental Abiotic Degradation:
The rate constant for the vapor-phase reaction
of toluene with photochemically-produced hydroxyl
radicals has been measured as 5.96X10-12 cu cm/molecule-sec at 25 deg C(1). This
corresponds to an atmospheric half-life of about 3 days at an atmospheric
concentration of 5X10+5 hydroxyl radicals per cu cm(1). The rate constant for
the vapor-phase reaction of toluene with nitrate
radicals has been measured as 6.8X10-17 cu cm/molecule-sec at 25 deg C(1). This
corresponds to an atmospheric half-life of about 491 days at an atmospheric
concentration of 2.4X10+8 nitrate radicals per cu cm(2). The rate constant for
the vapor-phase reaction of toluene with ozone has been
measured as 4.1X10-22 cu cm/molecule-sec at 25 deg C(1). This corresponds to an
atmospheric half-life of about 27,950 days at an atmospheric concentration of
7X10+11 ozone molecules per cu cm(3). Toluene is not
expected to undergo hydrolysis in the environment due to the lack of
hydrolyzable functional groups(4) nor to directly photolyze due to the lack of
absorption in the environmental UV spectrum.
Environmental Bioconcentration:
The BCF of toluene in
eels was reported as 13(1) and the BCF in golden ide was reported as 90(2).
According to a classification scheme(3), this BCF data suggests bioconcentration
in aquatic organisms is low to moderate.
Soil Adsorption/Mobility:
In association with clay minerals, toluene's
adsorption is inversely proportional to the pH of the soil. Approximately 40-70%
of toluene applied to the surface of sandy soils is
volatilized.
The Koc of toluene
was reported as 178 in a sandy soil(1) and as 37 (Wendover silty loam), 160
(Grimsby silt loam), 160 (Vaudreil sandy loam) and 46 (sandy soil)(2). The Koc
of toluene in lake sediment was measured as 166(3).
According to a classification scheme(4), this Koc data suggests that toluene
is expected to have high to moderate mobility in soil.
Volatilization from Water/Soil:
The Henry's Law constant for toluene
is 6.64X10-3 atm-cu m/mole(1). This Henry's Law constant indicates that toluene
is expected to volatilize rapidly 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 1 hour(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). Toluene's
Henry's Law constant(1) indicates that volatilization from moist soil surfaces
may occur(SRC). Toluene may volatilize from dry soil
surfaces based upon a vapor pressure of 28.4 mm Hg at 25 deg C(3).
Environmental Water Concentrations:
Toluene is detected
in 28% of National Priority List (NPL) sites in groundwater. Average
concentration: 5.18 ppm; Maximum concentration: 1100 ppm. /From table/
GROUNDWATER: Toluene
was detected in groundwater near contaminated wells from gasoline storage tanks
at concns of 0.55-6400 ppb(1,2) and groundwater underlying 2 rapid infiltration
sites at 0.2 ppb(3). Groundwater under a gasification site 15 months after
gasification contained toluene at 170-740 ppb(4). In a
cluster well study under an old industrial site, mean levels of toluene
in bedrock wells were 90 ppb while shallow and deep glacial wells were 10
ppb(5). Toluene was detected in 1.3% of the samples in
the US Ground Water Supply Survey, 1982, at a max concn of 2.9 ppb and a median
concn of 0.8 ppb(6).
DRINKING WATER: Toluene
was detected in 33% of the samples from 30 Canadian treatment facilities at an
avg concn of 2 ppb (14 ppb max) in summer months and in 53% of the samples at an
avg concn of <1 ppb (13 ppb max), during winter(1). Toluene
was detected at concns of 0-2 ppb in drinking water of cities supplied by the
Great Lakes(2). Toluene was detected in 14% of the
samples of drinking water in the US at concns of less than 1 part per
trillion(3). In a federal survey of finished drinking water from groundwater
sources toluene was detected in less than 5% of the
samples(4). Toluene was detected in 3 New Orleans area
water supplies at 0-10 ppb(5). Toluene was identified,
not quantified, in 60% of drinking water tested in the National Organics
Reconnaissance Survey(6). The max concn of toluene in
tapwater derived from bank-filtered Rhine River water was 1 ppb(7). Toluene
was detected in 3 contaminated drinking water wells in New Jersey at 55, 260,
6400 ppb whereas the highest concn in drinking water from surface water sources
was 6.1 ppb(8). Drinking water supplied from groundwater in England 210 m from a
gasoline storage tank contained 0.15 ppb of toluene(9).
In a 5-city survey in which the water supplies came from different types of
sources with various sources of pollution, 2 contained toluene,
one 0.1 ppb and the other 0.7 ppb(10). Toluene was
detected in 20 of 182 bottled water samples at an avg concn of 6.92 ug/kg and a
range of 0.5-63 ug/kg(11).
SURFACE WATER: Toluene
was detected in 31 of 204 sites at concns of 1-5 ppb in 14 heavily
industrialized river basins in the US(1). Toluene was
identified, not quantified, in various rivers(2-5). Toluene
was detected in the Gulf of Mexico at 3-376 parts per trillion(6,7) and the
Vineland Sound, MA at 10-54 parts per trillion(8). Toluene
was detected in the Elbe River, Germany at concns of 30-243 ng/l(9).
RAIN WATER: Toluene
was detected in rain in west Los Angeles at 76 parts per trillion(1). Toluene
was detected in 71.4% of the rain samples from 7 rain events in Portland, OR,
Feb-Apr 1984, at concns of 40-220 parts per trillion(2).
Effluent Concentrations:
Industries in which the mean effluent levels
exceed 1000 ppb are: auto and other laundries, iron and steel manufacturing, gum
and wood chemicals, pharmaceuticals, organic chemicals/plastics manufacturing,
paint and ink formulation. The highest mean value is 52 ppm for pharmaceuticals
and the highest maximum values are 230 and 260 ppm for pharmaceuticals and
organic chemicals/plastics manufacturing(1). Toluene
was detected in a plume from General Motors Paint Plant, Janesville, WI at 156
ppb(2). Auto exhaust contained toluene at concns of
196-718 mg/cu m(3).
Toluene was detected
in landfill gas emissions at concns of 20,400 ppb, 34,907 ppb and 76,700 ppb(1).
Toluene was detected in the gas emissions of 7 waste
disposal sites in the UK at concns of 10-287 mg/cu m(2). Toluene
was identified, not quantified, in the exhaust of a moped(3) and 4-stroke lawn
mower(4). Toluene was detected in car exhaust under
normal operating conditions at concns of 3.31-4.52 ppm and an avg of 3.83
ppm(5). The mean emission rate of toluene is 89-453
mg/km, with the lowest emission rates occurring at higher driving speeds(5). Toluene
was detected in the effluent of a hazardous waste incinerator in Germany at a
concn of 34 ug/cu m(6).
Sediment/Soil Concentrations:
SEDIMENT: Toluene was
identified, not quantified in sediment from rivers near industrial facilities in
the US(1,2). USEPA STORET DATABASE: Toluene was
detected in 67 of 397 sediment samples at a median concn of 5.0 ppb dry
weight(3). Toluene was detected in 33% of the sediment
samples from Lake Pontchartrain, LA at an avg concn of 0.7 ppb wet weight(4). Toluene
was detected at concns of less than 0.1 ng/g to 1.2 ng/g in sediment from rivers
near Niigata, Japan(5). Toluene was detected in
sediment of the Passaic River, NJ at concns of 3-250 ug/kg(6).
Atmospheric Concentrations:
URBAN/SUBURBAN: In a survey of 3,195 samples
obtained from urban areas in the US, toluene was
detected at concns of 0-85 ppb (11 ppb median)(1). Average toluene
concns in US cities range from 0.8-37 ppb with max values ranging from 6.5-1,110
ppb(2-9). Daily variations in concentrations and ratios of toluene
to benzene indicate that auto traffic is the most common source of atmospheric toluene(10,11,12).
Toluene was detected in Middelsbrough, UK and London,
UK at 1.55 and 7.475 ppb, respectively(13). The avg concn of toluene
inside buses and cars in Taipei, Taiwan was reported as 367 and 599 ug/cu m(14).
Toluene was detected in various streets in Europe at
concns of 87-127 ug/cu m(15). The concn of toluene
inside automobiles in Paris, France was 178-258 ug/cu m(16).
INDOOR AIR: Toluene
was detected at mean concns of 4.8 ug/cu m in telephone communications offices,
10.1 ug/cu m in data center offices and 5.7 ug/cu m in administrative offices in
the US(1). Toluene was detected in the volatile
emissions of newly installed carpet cushions at an emission rate of 4-79 ug/sq
m-hr during the first 6 hours after installation(2). Toluene
was detected in hairdresser salons in Norway at concns of 0.04-0.11 mg/cu m(3).
RURAL/REMOTE: Toluene
was detected in the atmosphere of 115 remote samples taken in the US at concns
of 0.057-30 ppb, (0.66 ppb median)(1). Toluene was
identified, not quantified, in a forest in Germany(2). Toluene
was detected in Langenbrugge, Germany and West Beckham, UK at concns of 0.441
and 0.999 ppb, respectively(3). Toluene was detected at
a concn of 0.04 ppb in Izana, Canaries(3)
SOURCE DOMINATED: In a survey of 188 source
dominated samples from the US, toluene was detected at
concns of 0.037-5,500 ppb (4.6 ppb median)(1). Toluene
was detected in the air of the Lipari and BFI landfills in NJ at 0.40 and 310
ppb(2). Toluene was detected at concns of 14-22 ppb 4
miles downwind from a General Motors paint plant(3). The avg concn of toluene
around gasoline pumps during fueling was in the range of 0.14-1.2 mg/cu m and
the fenceline concns at the filling stations were in the range of 0.005-0.02
ppm(4). Toluene was detected in the Fort McHenry
Tunnel, MD at concns of 79-90 ppb(5).
Food Survey Values:
Toluene was
identified, not quantified, in baked potatoes(1), mountain cheese(2), fried
bacon(3), fried chicken(4), peanut oil(5) and raw beef(6).
Plant Concentrations:
Toluene was
identified, not quantified, in the Korean Chamachwi plant(1).
Fish/Seafood Concentrations:
Flesh of fish from petroleum contaminated
harbor in Japan contained toluene at 5 ppm(1). Toluene
was detected in oysters from Lake Pontchartrain, LA at an avg concn of 3.4 ppb
and clams at concns of 18 and 11 ppb(2). Toluene was
identified, not quantified, in boiled shrimp and crab(3).
Milk Concentrations:
Toluene was
identified, not quantified, in 8 samples of mothers' milk from 4 urban areas(1).
Other Environmental Concentrations:
Light oil from coal 12-20% toluene;
crude oil 1.2-2.4% auto fuel 8-12%(1).
Evaporation from gasoline tank: 0.3 - 0.9 vol
% of total evaporated hydrocarbons; evaporation from carburetor: 0.5 - 2.4 vol %
of total evaporated hydrocarbons.
In exhaust of gasoline engines: 3-8 vol% of
total exhaust hydrocarbons; in exhaust of diesel engine: 3% of emitted
hydrocarbons; in exhaust of rotary gasoline engine: 16% of emitted hydrocarbons;
in exhaust of gasoline engine: 0.1-7.0 ppm (partly crotonaldehyde); in 4
municipal landfill gases in S. Finland (1989-1990): avg 0.23-137, max 143 mg/cu
m.
Environmental Standards & Regulations:
FIFRA Requirements:
Toluene is exempted
from the requirement of a tolerance when used as a solvent or cosolvent in
accordance with good agricultural practice as inert (or occasionally active)
ingredients in pesticide formulations applied to growing crops only.
TSCA Requirements:
Pursuant to section 8(d) of TSCA, EPA
promulgated a model Health and Safety Data Reporting Rule. The section 8(d)
model rule requires manufacturers, importers, and processors of listed chemical
substances and mixtures to submit to EPA copies and lists of unpublished health
and safety studies. Toluene is included on this list.
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 1000 lb or 454 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:
U220; As stipulated in 40 CFR 261.33, when toluene,
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).
F005; When toluene is
a spent solvent, it is classified as a hazardous waste from a nonspecific source
(F005), as stated in 40 CFR 261.31, and must be managed according to State
and/or Federal hazardous waste regulations.
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. Toluene
is produced, as an intermediate or a 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. Toluene
is included on this list.
Clean Water Act Requirements:
Toxic pollutant designated pursuant to section
307(a)(1) of the Federal Water Pollution Control Act and is subject to effluent
limitations.
Toluene 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.
For the protection of human health from the
toxic properties of toluene ... the ambient water
criterion is determined to be 14.3 mg/l.
The maximum contaminant level (MCL) set forth
by the National Revised Primary Drinking Water Regulations for the organic
contaminant toluene in community and non-transient,
non-community water systems is 1 mg/l.
Federal Drinking Water Standards:
EPA 1000 ug/l
Federal Drinking Water Guidelines:
EPA 1000 ug/l
State Drinking Water Standards:
(CA) CALIFORNIA 150 ug/l
(WI) WISCONSIN 1000 ug/l
State Drinking Water Guidelines:
(AZ) ARIZONA 2000 ug/l
(CT) CONNECTICUT 1000 ug/l
(FL) FLORIDA 40 ug/l
(ME) MAINE 1400 ug/l
(MN) MINNESOTA 1000 ug/l
(WA) WASHINGTON 800 ug/l
(WI) WISCONSIN 343 ug/l
FDA Requirements:
Toluene is an
indirect food additive for use only as a component of adhesives.
Allowable Tolerances:
Toluene is exempted
from the requirement of a tolerance when used as a solvent or cosolvent in
accordance with good agricultural practice as inert (or occasionally active)
ingredients in pesticide formulations applied to growing crops only.
Chemical/Physical Properties:
Molecular Formula:
C7-H8
Molecular Weight:
92.14
Color/Form:
Colorless liquid.
Odor:
Sweet, pungent, benezene-like odor.
Boiling Point:
110.6 deg C
Melting Point:
-94.9 deg C
Corrosivity:
Noncorrosive liquid.
Critical Temperature & Pressure:
Critical temperature: 591.75 K; Critical
pressure: 4.108 MPa
Density/Specific Gravity:
0.8636 @ 20 deg C/4 deg C
Heat of Combustion:
3910.3 KJ/mol
Heat of Vaporization:
38.01 KJ/mol @ 25 deg C
Octanol/Water Partition Coefficient:
log Kow= 2.73
Solubilities:
Miscible with alcohol, chloroform, ether,
acetone, glacial acetic acid, carbon disulfide
Soluble in ethanol, benzene, diethyl ether,
acetone, chloroform, glacial acetic acid and carbon disulfide; insoluble in
water.
In water, 526 mg/l @ 25 deg C
Spectral Properties:
SADTLER REF NUMBER: 419 (IR, PRISM); 119 (IR,
GRATING); MAX ABSORPTION (ALCOHOL): 207 NM (LOG E= 3.97); 260 NM LOG E= 2.48)
Index of refraction: 1.4967 @ 20 deg C/D
IR: 3574 (Coblentz Society Spectral
Collection)
UV: 155 (Sadtler Research Laboratories
Spectral Collection)
NMR: 157 (Varian Associates NMR Spectra
Catalogue)
MASS: 189 (Atlas of Mass Spectral Data, John
Wiley & Sons, New York)
Intense mass spectral peaks: 65 m/z, 91 m/z,
92 m/z
Surface Tension:
29.71 dyne/cm @ 10 deg C; 28.93 dyne/cm @ 20
deg C; 24.96 dyne/cm @ 50 deg C; 21.98 dyne/cm @ 75 deg C; 19.01 dyne/cm @ 100
deg C
Vapor Density:
3.1 (Air=1)
Vapor Pressure:
28.4 mm Hg @ 25 deg C
Viscosity:
0.778 cP @ 0 deg C; 0.560 cP @ 25 deg C; 0.424
cP @ 50 deg C; 0.333 cP @ 75 deg C; 0.270 cP @ 100 deg C
Other Chemical/Physical Properties:
CONVERSION FACTORS: 1 PPM= 3.76/CU M; 1 MG/L=
226 PPM.
Ratio of Specific Heats of Vapor (Gas): 1.089;
floats on water
Partition coefficients at 37 deg C for toluene
into blood= 15.6; into oil= 1,470.
Henry's Law constant = 6.64X10-3 atm-cu m/mole
@ 25 deg C
Hydroxyl radical rate constant = 5.96X10-12 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 or
confined areas (sewers, basements, tanks). Vapor explosion hazard indoors,
outdoors or in sewers. Some may polymerize (P) explosively when heated or
involved in a fire. Runoff to sewer may create fire or explosion hazard.
Containers may explode when heated. Many liquids are lighter than water.
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 Numbers. ... Isolate spill or leak area immediately for at least 50 to
100 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: Large spill: Consider initial
downwind evacuation for at least 300 meters (1000 feet). Fire: If tank, rail car
or tank truck is involved in a fire, isolate for 800 meters (1/2 mile) in all
directions; also, consider initial evacuation for 800 meters (1/2 mile) in all
directions.
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 regular foam. Large fires: Water spray,
fog or regular foam. Do not use straight streams. Move containers from fire area
if you can do it without risk. Fire involving tanks or car/trailer loads: Fight
fire from maximum distance or use unmanned hose holders or monitor nozzles. Cool
containers with flooding quantities of water until well after fire is out.
Withdraw immediately in case of rising sound from venting safety devices or
discoloration of tank. Always stay away from the ends of tanks. For massive
fire, use unmanned hose holders or monitor nozzles; if this is impossible,
withdraw from area and let fire burn.
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
emergency medical care. Apply artificial respiration if victim is not breathing.
Administer oxygen if breathing is difficult. Remove and isolate contaminated
clothing and shoes. In case of contact with substance, immediately flush skin or
eyes with running water for at least 20 minutes. Wash skin with soap and water.
Keep victim warm and quiet. 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:
2.14 ppm (8 mg/cu m). Odor recognition level
is reported as 1.03 to 140 ug/cu m.
Odor in air= 1.30x10+11 mol/cu cm
Skin, Eye and Respiratory Irritations:
A human eye irritant. An experimental skin and
severe eye irritant.
Fire Potential:
Flammable liquid. A very 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: 1.1% by volume; Upper
flammable limit: 7.1% by volume
Flash Point:
40 deg F (4 deg C) (Closed cup)
16 deg C (Open cup)
Autoignition Temperature:
896 DEG F (480 DEG C)
Fire Fighting Procedures:
TO FIGHT FIRE, USE FOAM, CO2, DRY CHEMICAL.
Approach fire from upwind to avoid hazardous
vapors and toxic decomposition
If material on fire or involved in fire: Do
not extinguish fire unless flow can be stopped or safely confined. 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.
Toxic Combustion Products:
MODERATELY DANGEROUS; WHEN HEATED, EMITS TOXIC
FUMES /WHICH/ CAN REACT VIGOROUSLY WITH OXIDIZING MATERIALS.
Firefighting Hazards:
Vapor is heavier than air and may travel a
considerable distance to a source of ignition and flash back.
Flame speed equals 37 cm/sec.
Explosive Limits & Potential:
LEL: 1.27%; UEL: 7%.
Hazardous Reactivities & Incompatibilities:
Frozen bromine trifluoride reacts violently
with toluene at -80 deg C.
A mixture of /dinitrogen/ tetraoxide and toluene
exploded, possibly initiated by impurities.
Lack of proper control in nitration of toluene
with mixed acids /nitric/ may lead to runaway or explosive reaction. A
contributory factor is the oxidative formation, and subsequent nitration and
decomposition of nitrocresols.
When /tetranitromethane is/ mixed with
hydrocarbons in approximately stoichiometric proportions, a sensitive highly
explosive mixture is produced which needs careful handling ... . Explosion of
only 10 g of a mixture with toluene caused 10 deaths
and 20 severe injuries. The mixture contained excess toluene
in error.8
Interaction /of uranium hexafluoride/ with ...
toluene ... is very vigorous, with separation of
carbon, and violent with ethanol or water.
Incompatible with strong oxidizers.
Strong oxidizers.
Reacts photochemically with nitrogen oxides or
halogens to form nitrotoluene, nitrobenzene and nitrophenol and halogenated
products, respectively.
Explosive reaction with
1,3-dichloro-5,5-dimethyl-2,4-imidazolididione; dinitrogen tetraoxide;
concentrated nitric acid, sulfuric acid + nitric acid; N2O4; AgClO4; BrF3;
Uranium hexafluoride; sulfur dichloride. Forms an explosive mixture with
tetranitromethane.
Hazardous Decomposition:
When heated to decomposition it emits acrid
smoke and irritating fumes.
Prior History of Accidents:
The wreck of the MV Ariadne, a Panamanian flag
container ship, is examined as a case study of a hazardous substance emergency
response in a third world country. /The ship/, carrying a cargo of heavy fuel
oil, tetraethyl lead, xylene, toluene, methyl isobutyl
ketone, butyl acetate, ethyl acetate, and acetone was grounded while departing
the harbor of Mogadishu, Somalia. The Somalian government requested a team of
technical advisors to help respond appropriately to the emergency. The major
issues addressed by the advisory team were the need for additional salvage
equipment and expertise, the danger of toxic fumes from the fire and explosions
aboard the ship, the presence and possible release of tetraethyl lead, possible
port blockage by the wreck, recovery of the chemical drums, and the extent of
environmental damage caused by the release of oil, pesticides, and tetraethyl
lead into the harbor. ...
Immediately Dangerous to Life or Health:
500 ppm
Protective Equipment & Clothing:
Protective clothing should include gloves,
barrier creams, eye goggles or face shields, and a cartridge-type or
self-contained breathing apparatus.
WEAR SELF-CONTAINED BREATHING APPARATUS; WEAR
GOGGLES IF EYE PROTECTION NOT PROVIDED.
Eye protection: Glasses having
shatter-resistant glass or equivalent lenses and side shields to protect the
eyes from toluene splashes.
If, for the purpose of maintenance or
cleaning, a person is required to enter a vessel or similar area which has
contained toluene, all suitable precautions for work in
confined spaces should be adopted. Respiratory protection of the airline or
self-contained type is essential; Reliance should not be placed on a canister
respirator for such work. Workers whose hands may be exposed to toluene
should wear suitable gloves or barrier creams. A thick layer of barrier cream
should be applied. Under certain circumstances the use of a mask may be
necessary for this type of work.
Respirator selection: 500 ppm: Chemical
cartridge respirator with organic vapor cartridge/supplied-air
respirator/self-contained breathing apparatus; 1000 ppm: Chemical cartridge
respirator with organic vapor cartridge with full facepiece; 2000 ppm: Gas mask
with organic vapor canister/supplied-air respirator with full facepiece, helmet,
or hood/self-contained breathing apparatus with full facepiece; Escape: gas mask
with organic vapor canister/self-contained breathing apparatus.
Wear appropriate personal protective clothing
to prevent skin contact.
Wear appropriate eye protection to prevent eye
contact.
Recommendations for respirator selection. Max
concn for use: 500 ppm. Respirator Class(es): Any chemical cartridge respirator
with organic vapor cartridge(s). May require eye protection. Any powered,
air-purifying respirator with organic vapor cartridge(s). May require eye
protection. Any air-purifying, full-facepiece respirator (gas mask) with a
chin-style, front- or back-mounted organic vapor canister. Any supplied-air
respirator. May require eye protection. Any self-contained breathing apparatus
with a full facepiece.
Recommendations for respirator selection.
Condition: Emergency or planned entry into unknown concn or IDLH conditions:
Respirator Class(es): Any self-contained breathing apparatus that has a full
facepiece and is operated in a pressure-demand or other positive-pressure mode.
Any supplied-air respirator that has a full facepiece and is operated in a
pressure-demand or other positive-pressure mode in combination with an auxiliary
self-contained breathing apparatus operated in pressure-demand or other
positive-pressure mode.
Recommendations for respirator selection.
Condition: Escape from suddenly occurring respiratory hazards: Respirator
Class(es): Any 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.
Preventive Measures:
Drench-type showers, eye-wash fountains should
be installed and maintained to provide prompt, immediate access.
Open lights or other agencies liable to ignite
the vapor should be excluded from areas where the liquid is liable to be exposed
in use or by accident.
A major concern in the painting studio is
solvents, /including toluene/. ... Precautions include
... use of dilution and local exhaust ventilation, control of storage areas,
disposal of solvent soaked rags in covered containers, minimizing skin exposure
and the use of respirators and other personal protective equipment. The control
of fire hazards is also important, since many of the solvents are highly
flammable.
Contact lenses should not be worn when working
with this chemical.
SRP: The scientific literature for the use of
contact lenses in industry is conflicting. The benefit or detrimental effects of
wearing contact lenses depend not only upon the substance, but also on factors
including the form of the substance, characteristics and duration of the
exposure, the uses of other eye protection equipment, and the hygiene of the
lenses. However, there may be individual substances whose irritating or
corrosive properties are such that the wearing of contact lenses would be
harmful to the eye. In those specific cases, contact lenses should not be worn.
In any event, the usual eye protection equipment should be worn even when
contact lenses are in place.
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.
If material leaking (not on fire): Consider
evacuation from downwind area based on amount of material spilled, location and
weather conditions.
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.
Shipment Methods and Regulations:
No person may /transport,/ offer or accept a
hazardous material for transportation in commerce unless that person is
registered in conformance ... and the hazardous material is properly classed,
described, packaged, marked, labeled, and in condition for shipment as required
or authorized by ... /the hazardous materials regulations (49 CFR 171-177)./
The International Air Transport Association (IATA)
Dangerous Goods Regulations are published by the IATA Dangerous Goods Board
pursuant to IATA Resolutions 618 and 619 and constitute a manual of industry
carrier regulations to be followed by all IATA Member airlines when transporting
hazardous materials.
The International Maritime Dangerous Goods
Code lays down basic principles for transporting hazardous chemicals. Detailed
recommendations for individual substances and a number of recommendations for
good practice are included in the classes dealing with such substances. A
general index of technical names has also been compiled. This index should
always be consulted when attempting to locate the appropriate procedures to be
used when shipping any substance or article.
Storage Conditions:
Outside or detached storage is preferred.
Inside storage should be in a standard flammable liquids storage warehouse,
room, or cabinet. Separate from oxidizing materials.
Use ambient storage temperature.
Cleanup Methods:
Eliminate all ignition sources. Stop or
control the leak, if this can be done without undue risk. Use water spray to
cool and disperse vapors and protect personnel. Absorb in noncombustible
material for proper disposal. Control runoff and isolate discharged material for
proper disposal.
1. REMOVE ALL IGNITION SOURCES. 2. VENTILATE
AREA OF SPILL OR LEAK. 3. FOR SMALL QUANTITIES, ABSORB ON PAPER TOWELS.
EVAPORATE IN SAFE PLACE (SUCH AS FUME HOOD). ALLOW SUFFICIENT TIME FOR
EVAPORATING VAPORS TO COMPLETELY CLEAR HOOD DUCTWORK. BURN PAPER IN SUITABLE
LOCATION AWAY FROM COMBUSTIBLE MATERIALS.
Fluorocarbon water foam may be used to
diminish vapors and provide wet down.
Cellosive and hycar absorbent materials, may
be used for vapor suppression and/or containment of toluene.
Treat contaminated water by gravity separation
of solids, followed by skimming of surface. Pass through dual media filtration
and carbon adsorption units (carbon ratio 1.0 kg to 10.0 kg soluble material).
Return waste water from backwash to gravity separator.
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 barriers or oil spill control boom to limit spill travel. Use
surface active agent (eg Detergent, soaps, alcohols), if approved by EPA. Inject
"universal" gelling agent to solidify encircled spill and increase
effectiveness of booms. 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.
Environmental considerations - Air Spill:
Apply water spray or mist to knock down vapors.
Disposal Methods:
Generators of waste (equal to or greater than
100 kg/mo) containing this contaminant, EPA hazardous waste numbers U220, and
F005 must conform with USEPA regulations in storage, transportation, treatment
and disposal of waste.
Toluene is a waste
chemical stream constituent which may be subjected to ultimate disposal by
controlled incineration.
A good candidate for liquid injection
incineration at a temperature range of 650 to 1,600 deg C and a residence time
of 0.1 to 2 seconds. A good candidate for rotary kiln incineration at a
temperature range of 820 to 1,600 deg C and residence times of seconds for
liquids and gases, and hours for solids. A good candidate for fluidized bed
incineration at a temperature range of 450 to 980 deg C and residence times of
seconds for liquids and gases, and longer for solids.
Additional flammable solvent may be added to
increase incineration efficiency. Following treatment at a spill site or waste
management facility, the resultant sludge can be disposed of to a secure
landfill.
LARGE QUANTITIES CAN BE RECLAIMED OR COLLECTED
& ATOMIZED IN SUITABLE COMBUSTION CHAMBER. TOLUENE
SHOULD NOT BE ALLOWED TO ENTER A CONFINED SPACE, SUCH AS SEWER, BECAUSE OF
POSSIBILITY OF EXPLOSION. ... DISPOSAL METHODS: TOLUENE
MAY BE DISPOSED OF BY ATOMIZING IN SUITABLE COMBUSTION CHAMBER.
The following wastewater treatment
technologies have been investigated for toluene:
biological treatment.
The following wastewater treatment
technologies have been investigated for toluene:
stripping.
The following wastewater treatment
technologies have been investigated for toluene:
solvent extraction.
The following wastewater treatment
technologies have been investigated for toluene:
activated carbon.
Occupational Exposure Standards:
OSHA Standards:
Permissible Exposure Limit: Table Z-2 8-hr
Time Weighted Avg: 200 ppm.
Permissible Exposure Limit: Table Z-2
Acceptable Ceiling Concentration: 300 ppm.
Permissible Exposure Limit: Table Z-2
Acceptable maximum peak above the acceptable ceiling concentration for an 8-hour
shift. Concentration: 500 ppm. Maximum Duration: 10 minutes.
Vacated 1989 OSHA PEL TWA 100 ppm (375 mg/cu
m); STEL 150 ppm (560 mg/cu m) is still enforced in some states.
Threshold Limit Values:
8 Hr Time Weighted Avg (TWA) 50 ppm, skin
Biological Exposure Index (BEI): Hippuric acid
in urine at end of shift is 1.65 g/g creatinine. The determinant is usually
present in a significant amt in biological specimens collected from subjects who
have not been occupationally exposed. Such background levels are incl in the BEI
value. The determinant is nonspecific, since it is observed after exposure to
some other chemicals. These nonspecific tests are preferred because they are
easy to use and usually offer a better correlation with exposure than specific
tests. In such instances, a BEI for a specific, less quantitative biological
determinant is recommended as a confirmatory test.
Biological Exposure Index (BEI) adoption
(1998): Toluene in venous blood prior to last shift of
workweek is 0.5 mg/l.
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.
Biological Exposure Index (BEI): Determinant:
o-Cresol in urine; Sampling Time: end of shift; BEI:0.5 mg/L. The determinant is
usually present in a significant amt in biological specimens collected from
subjects who have not been occupationally exposed. Such background levels are
incl in the BEI value.
A4. A4= Not classifiable as a human
carcinogen.
NIOSH Recommendations:
Recommended Exposure Limit: 10 Hr
Time-Weighted Avg: 100 ppm (375 mg/cu m).
Recommended Exposure Limit: 15 Min Short-Term
Exposure Limit: 150 ppm (560 mg/cu m).
Immediately Dangerous to Life or Health:
500 ppm
Other Occupational Permissible Levels:
Australia: 100 ppm, STEL 150 ppm (substance
under review) (1990); Federal Republic of Germany: 100 ppm, short-term level 500
ppm, 30 min, twice per shift, Pregnancy group B, a risk of damage to the
developing embryo or fetus must be considered to be probable (1992); Sweden: 80
ppm, short-term value 100 ppm, 15 min, planning of new plants or alterations of
old ones, 50 ppm (1990); United Kingdom: 50 ppm, 10-min STEL 150 ppm, skin
(1991).
Emergency Response Planning Guidelines (ERPG):
ERPG(1) 50 ppm (no more than mild, transient effects) for up to 1 hr exposure;
ERPG(2) 300 ppm (without serious, adverse effects) for up to 1 hr exposure;
ERPG(3) 1000 ppm (not life threatening) up to 1 hr exposure.
Manufacturing/Use Information:
Major Uses:
In manufacture benzoic acid, benzaldehyde,
explosives, dyes, and many other organic compounds; as a solvent for paints,
lacquers, gums, resins, in the extraction of various principles from plants; as
gasoline additive.
DILUENT FOR PHOTOGRAVURE INKS
IN FABRIC & PAPER COATING, MFR ARTIFICIAL
LEATHER
Used in cements, solvents, spot removers,
cosmetics, antifreezes, and inks.
Asphalt and naphtha constituent. Detergent
manufacture.
Mfg benzene derivatives, caprolactam,
saccharin, medicines, dyes, perfumes, TNT; solvent recovery plants; component of
gasoline; solvent for paints and coatings, gums, resins, rubber and vinyl
organosol; diluent and thinner in nitrocellulose lacquers; adhesive solvent in
plastic toys and model airplanes; detergent mfg; gasoline and naphtha
constituent.
Fuel blending
DENATURANT
The largest chemical use for toluene
is the production of benzene and urethane via hydrodealkylation.
Used in production of drugs of abuse.
Manufacturers:
Amoco Corp., 200 East Randolph Drive, Chicago,
IL 60601, (312)856-6111; Production site: Texas City, TX 77590
BP America, 200 Public Square, Cleveland OH
44114-2375. (216) 586-4141; Production sites: Alliance, LA 70037; Lima, OH 45804
CITGO Petrochemical Co., 6130 S. Yale Ave.,
Tulsa, OK 74136, (918)495-4000; Production sites: Corpus Christi, TX 78469; Lake
Charles, LA 70601; Lemont, IL 60439-3659
Coastal Refining and Marketing, 9 Greenway
Plaza, Houston, TX 77046, (713)877-6559; Production site: Corpus Christi, TX
78403
Coastal Eagle Point Co., 9 PO Box 1000, US
Route 130& I295 Westville, NJ 08093, (609)853-3100; Production site:
Westville, NJ 08093
Chevron Chemical Corp., 6001 Bollinger Canyon
Rd., San Ramon, CA 94583, (925)842-5500; Production site: Port Arthur, TX 77460
Dow Chemical USA, 2020 Dow Center, Midland, MI
48674, (517) 636-1000; Production site: Plaquemine, LA 70765
Equistar Chemicals LP., One Houston Center,
1221 McKinney St., Suite 1600, Houston, TX 77010, (713)652-7300; Production
sites: Alvin, TX 77511; Channelview, TX 77530; Corpus Christi, TX 78410
Exxon Chemical Co., 13501 Katy Freeway,
Houston, TX 77079, (281)871-6000; Production site: Baton Rouge, LA 70821
Fina Oil and Chemical Co., PO Box 2159,
Dallas, TX 75221-2159, (214) 750-2400; Production site: Port Arthur, TX 77460
Hess Oil Virgin Islands Corp., Kings Hill Rd.,
P.O. Box 127 Kingshill, VI 00851-0127, (340)778-4000; Production site: St.
Croix, VI 00850
Koch Refining Co., PO Box 2256, Wichita, KS
67201, (316)828-5500; Production site: Corpus Christi, TX 78403
Lyondell-CITGO Refining Co., 1200 Lawndale,
Houston, TX 77017, (713)321-4111; Production site: Houston, TX 77252
Marathon Ashland Petroleum LLC., 539 South
Main St., Findlay, OH 45840-3295, (419) 422-2121; Production sites:
Catlettsburg, KY 41129; Texas City, TX 77592-1191
Mobil Chemical Co., 3225 Gallows Rd., Fairfax,
VA 22037-0001, (703)846-3000; Production sites: Chalmette, LA 70043; Beaumont,
TX 77704-3868
Phillips Petroleum Co., Phillips Building,
Bartlesville, OK 74004, (918)661-6600; Production site: Sweeney, TX 77480
Phillips Puerto Rico Core Inc., Road 3 Route
710, Barrio Las Mareas Guayama PR 00785, (787)864-1515; Production site: Guayama,
PR 00785
Shell Chemical Co., One Shell Plaza, PO Box
2463, Houston, TX 77252-2463, (713)241-6161; Production site: Deer Park, TX
77536
Sun Company Inc., 1801 Market St.,
Philadelphia, PA 19103, (800) 825-3535; Production sites: Marcus Hook, PA 19061;
Toledo, OH 43693; Tulsa, OK 74102
Texaco Refining and Marketing Inc., 10
Universal City Plaza, Universal City, CA 91608-1097, (818)505-2000; Production
site: El Dorada, KS 67042
Ultramar Diamond Corp., 6000 N. Loop 1604, W.
San Antonio, TX 78249-1112, (210)592-2000; Production site: Three Rivers, TX
78071
Valero Energy Corp., San Antonio Valero Tower,
W 1H 10, San Antonio, TX 78229-4718, (210)370-2000; Production site: Houston, TX
77012-2408
Methods of Manufacturing:
UNRECOVERED COMPONENT OF GASOLINE
Catalytic reforming of petroleum steams
accounts for 87% of total toluene production. An
additional 9% is separated from pyrolysis gasoline produced in steam crackers
during manufacture of ethylene and propylene ... coal-tar separation from coke
ovens produces 1% of total toluene ... up to 2% of the toluene
produced is obtained as a by-product from styrene manufacture.
(1) By catalytic reforming of petroleum. (2)
By fractional distillation of coal tar light oil.
General Manufacturing Information:
28th Highest-volume chemical produced in the
USA (1995).
Formulations/Preparations:
Research, reagent, nitration - all 99.8+%;
Industrial: Contains 94+%, with 5% xylene and small amounts of benzene and
nonaromatic hydrocarbons; 90/120: Less pure than industrial.
Grades: Research 99.99%; Pure 99.98%
Grades: 1st degree nitration; 2nd degree
commercial; 90% solvent
Grade: (Usually defined in terms of boiling
ranges) Pure, commercial, straw-colored, nitration, scintilation, industrial.
Impurities:
... Commercial grades /of toluene/
usually contain small amounts of benzene as an impurity.
Technical grades (90-120 deg C boiling range)
are less pure and may contain up to 25% benzene as well as other hydrocarbons.
Commercial grades /of toluene/
can ... contain polynuclear aromatic hydrocarbons (PAH), including pyrene,
fluoranthrene, and benzo[ghi]perylene.
Consumption Patterns:
CHEM INT FOR BENZENE, 55.3%; SOLVENT, 25.7%;
CHEM INT FOR TOLUENE DIISOCYANATE, 7.3%; CHEM INT FOR
BENZOIC ACID, 2.5%; CHEM INT FOR BENZYL CHLORIDE, 1.5%; OTHER, 7.7% (1981
NON-GASOLINE USE)
Benzene, 46%; gasoline blending, 37%; solvent,
8%; toluene diisocyanate, 7%; miscellaneous chemicals,
2% (1985) /estimate/
In the USA in 1981, the use of toluene
as a solvent was second only to its use in benzene production via
hydrodemethylation and accounted for about 26% of nonfuel consumption.
Of the estimated 3.3 million tons of toluene
produced in the USA in 1980, 44% was used to make benzene, 34% to make gasoline,
10% in solvents, 6% to make toluene diisocyanate, and
6% for miscellaneous use.
Laboratory Methods:
Clinical Laboratory Methods:
NIOSH Method: 8002. Analyte: Toluene.
Specimen: Venous blood, after 2 or more hours of exposure. Procedure: Gas
chromatography, hydrogen-air flame ionization detector. The precision/RSD is
0.098 (1 ug/ml blood) and the recovery is 0.93 @ 2 ug/ml blood. The working
range is 1 to 600 ug/ml. Applicability: Toluene is
commonly found in trace amounts in humans working in the paint spray industry.
Interferences: Ethanol in excess of the stated range increased blood toluene
concentration. When substances other than the analytes are present in the blood,
record their identities to determine possible interferences.
A procedure for the determination of toluene
in blood by the purge and trap method is described ... has a linear range which
extends up to at least 1500 ug/l ... detection limit ... is estimated to be less
than 7.5 ug/l ...
An automated high performance liquid
chromatographic method for the direct determination of urinary concentrations of
p-methylhippuric acids, and metabolites of toluene is
described. A mixed solution of 5 mM potassium phosphate monobasic/acetonitrile
(90/10) was used as a mobile phase . The method is simple and specific. Urine
can be analyzed without solvent extraction.
Analytic Laboratory Methods:
Quantitative determination of 4 to 40 ppm toluene
in water with precision of 10% using IR spectroscopy.
Quantitative method for detection of toluene
in water by gas chromatography. Levels over 1 ppm can be detected.
TOLUENE WAS
IDENTIFIED IN WASTE-CONTAMINATED SOIL AND CHEMICAL STILL BOTTOM EXTRACTS BY
GC/FOURIER TRANSFORM INFRARED SPECTROMETRY.
TWENTY AQ INDUST EFFLUENTS CONTAINING
POLLUTANTS WERE ANALYZED USING ISOTOPE DILN & GC/MASS SPECTROMETRY. TOLUENE
WAS ONE OF THE POLLUTANTS.
NIOSH Method 1500. Analyte: Toluene.
Matrix: Air. Procedure: Gas chromatography hydrogen-air flame ionization
detector. For toluene this method has an estimated
detection limit of 0.001 to 0.01 mg/sample with capillary column/sample. The
overall precision/RSD is 0.011. Applicability: This method is intended for
determining the OSHA-regulated hydrocarbons included within the boiling point
range of n-pentane through n-octane. Interferences: At high humidity,
breakthrough volumes may be reduced by as much as 50%.
NIOSH Method 4000. Analyte: Toluene.
Procedure: Gas chromatography, hydrogen-air flame ionization detector. For toluene
this method has an estimated detection limit of 0.01 mg/sample. The overall
precision/RSD is 0.022. Applicability: The working range is 13 to 660 ppm (50 to
2500 mg/cu m) for a 4 hr sample. Interferences: None identified.
NIOSH Method 1501. Analyte: Toluene.
Matrix: Air. Procedure: Gas chromatography, hydrogen-air flame ionization
detector. For toluene this method has an estimated
detection limit of 0.001 to 0.01 mg/sample with capillary column/sample. The
overall precision/RSD is 0.011. Applicability: This method is for peak, ceiling
and TWA determinations of aromatic hydrocarbons. Interferences: Use of the
recommended column will prevent interferences by alkanes (less or equal to C10).
EPA Method 524.1. Purge-and-Trap Gas
Chromatography/Mass Spectrometry. The method is applicable for the determination
of volatile organic compounds in water, finished drinking water, raw source
water, or drinking water in any treatment stage. For toluene
the method has a detection limit of 0.08 ug/l and a standard deviation of 4.1%.
EPA Method 524.2. Purge-and-Trap Gas
Chromatography/Mass Spectrometry for the determination of volatile aromatic
compounds in water including finished drinking water, raw source water, and
drinking water in any treatment stage. For toluene the
method has a detection limit of 0.11 ug/l and a relative standard deviation of
8.0% with a wide bore capillary column, and a method detection limit of 0.08 ug/l
and a relative standard deviation of 5.9% with a narrow bore capillary column.
EPA Method 602. Purge-and-Trap Gas
Chromatography with photoionization detection for the determination of purgeable
aromatics including toluene in municipal and industrial
discharges. Under the prescribed conditions for toluene
the detection limit is 0.2 ug/l. The method is applicable for use in the
concentration range from the method detection limit to 100 times that limit.
Precision and method accuracy were found to be directly related to the
concentration of the analyte essentially independent of the sample matrix.
EPA Method 624. Purge-and-Trap Gas
Chromatography/Mass Spectrometry for the analysis of purgeable organics
including toluene in the municipal and industrial
discharges. Under the prescribed conditions, for toluene
the method has a detection limit of 6.0 ug/l. Precision and method accuracy were
found to be directly related to the concentration of the analyte and essentially
independent of the sample matrix.
EPA Method 1624. Isotope Dilution
Purge-and-Trap Gas Chromatography/Mass Spectrometry. This method is applicable
for the determination of volatile organic compounds in municipal and industrial
discharges. By adding a known amount of a labeled compound to every sample prior
to purging, a correction of recovery of the pollutant can be made. If labeled
compounds are not available, an internal standard method is used. Under the
prescribed conditions, for both the labeled, and unlabeled ethylbenzene the
method has a minimum detection level 10 ug/l.The established acceptance
performance criteria at 20 ug/l is 6.2 ug/l for the standard deviation of the
recovery, with the average recovery of 14.5 to 28.7 ug/l and the labeled cmpd
recovery ranging from 4 to 193%.
EPA Method 8020. Direct Injection or
Purge-and-Trap Gas Chromatograpy with photoionization detection for the
determination of aromatic volatile organics including toluene
in solid waste. Under the prescribed conditions, for toluene
the method has a detection limit of 0.2 ug/l. Precision and method accuracy were
found to be directly related to the concentration of the analyte and essentially
independent of the sample matrix.
EPA Method 8240. Gas Chromatography/Mass
Spectrometry for the determination of volatile Organics. This method can be used
to quantify most volatile organic compounds including toluene
that have boiling points below 200 deg C and are insoluble or slightly soluble
in water. The detection limit is not given. Precision and method accuracy were
found to be directly related to the concentration of the analyte and essentially
independent of the sample matrix.
EPA Method 502.2: Purge-and-Trap Capillary
Column Gas Chromatography with Photoionization and Electrolytic Conductivity
Detectors in Series. The method is applicable for the determination of volatile
organic compounds in finished drinking water, raw source water, or drinking
water in any treatment stage. For toluene the method
has a detection limit of 0.01 ug/l, a percent recovery of 99%, and a standard
deviation of 1.9 using the photoionization detector.
EPA Method 502.1. Purge and Trap Gas
Chromatography with a halogen-specific detector for the determination of
halogenated volatile compounds including toluene in
finished drinking water, raw source water, or drinking water in any treatment
stage. Under the prescribed conditions for toluene, the
method detection limit is 0.02 ug/l.
AOB Method OA-002-1. Volatile Organic
Compounds by GC/MS Analysis of Tenax/CMS Cartridge and Summa Canister Samples.
No detection limit.
AOB Method VA-001-1. Volatile Organic
Compounds (VOCs) in Air Sampled by Sorbent Tubes and Analyzed by Purge and Trap
GC. No detection limit.
AOB Method VA-003-1. Volatile Organic
Compounds (VOCs) in Air by Portable GC/PID. No detection limit.
AOB Method VA-005-1. Volatile Organic
Compounds (VOCs) in Ambient Air by Purge and Trap Gas Chromatography. No
detection limit.
AOB Method VA-006-1. Volatile Organic
Compounds (VOCs) in Ambient Air by Direct Portable GC/PID. No detection limit.
AOB Method VA-007-1. Volatile Organic
Compounds (VOCs) in Ambient Air by GC/PID, GC/PID/FID, or GC/FID. No detection
limit.
AOB Method VA-008-1. Volatile Organic
Compounds (VOCs) in Ambient Air by Portable GC/PID with Direct Sampling via Pump
and Sample Loop. No detection limit.
AOB Method VG-001-1. Volatile Organics in Soil
Gas - Adsorbent Tube Method. No detection limit.
AOB Method VG-006-1. Volatile Organic
Compounds (VOCs) in Ambient Air by Purge and Trap GC. No detection limit.
AOB Method VG-007-1. Halogenated and Aromatic
Volatile Organic Compounds (VOCs) in Air and Soil Gas Sampled by Sorbent Tubes
and Analyzed by Purge and Trap GC/ELCD/PID. No detection limit.
AOB Method VG-008-1 . Volatile Organic
Compounds (VOCs) in Soil Gas sampled by Tenax Tubes and Analyzed by Thermal
Desorption GC/PID/ELCD. No detection limit.
AOB Method VG-010-1. Volatile Organic
Compounds (VOCs) in Soil Gas by Direct Portable GC. No detection limit.
AREAL Method IP-1A . Determination of Volatile
Organic Compounds (VOCs) in Indoor Air Using Stainless Steel Canisters. No
detection limit.
AREAL Method IP-1B . Determination of Volatile
Organic Compounds (VOCs) in Indoor Air using Solid Absorbent Tubes. No detection
limit.
AREAL Method TO-1 . Determination of Volatile
Organic Compounds in Ambient Air using Tenax Adsorption and Gas
Chromatography/Mass Spectrometry (GC/MS). No detection limit.
AREAL Method TO-2 . Determination of Volatile
Organic Compounds In Ambient Air by Carbon Molecular Sieve Adsorption and Gas
Chromatography/Mass Spectrometry (GC/MS). No detection limit.
AREAL Method TO-14. Determination of Volatile
Organic Compounds (VOCs) in Ambient Air using SUMMA Passivated Canister Sampling
and Gas Chromatographic Analysis. No detection limit.
Sampling Procedures:
... Personal dosimeter type badge monitor
collects organic vapors ... /for analysis/ using gas chromatographic techniques
... sampled over the range of 0.5 ppm-1100 ppm /organic vapors/
NIOSH Method 1500. Analyte: Toluene.
Matrix: Air. Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg).
Flow Rate: 0.20 l/min. Sample Size: 8 liters. Shipment: No special precautions.
Sample Stability: At least 2 weeks.
NIOSH Method 4000. Analyte: Toluene.
Sampler: Passive (activated carbon). Shipment: Transfer sorbent to septum-capped
vial; otherwise routine. Sample Stability: At least 2 weeks @ 25 deg C if stored
in septum-capped vial.
NIOSH Method 8002. Analyte: Toluene.
Specimen: Venous blood, after 2 or more hrs of exposure. Shipment: Air express @
4 deg C. Sample Stability: Stable @ 4 deg C for 3 weeks.
NIOSH Method 1501. Analyte: Toluene.
Matrix: Air. Sampler: Solid sorbent tube (coconut shell charcoal, 100 mg/50 mg).
Flow Rate: Less or equal to 0.20. Sample Size: 8-liters. Shipment: No special
precautions. Sample Stability: Not determined.
Special References:
Special Reports:
REVIEW: BENIGNUS VA; NEUROTOXICOLOGY (PARK
FOREST SOUTH, ILL) 2 (3): 567 (1981). REVIEW ON HEALTH EFFECTS OF TOLUENE,
PARTICULARLY WITH RESPECT TO ITS NEUROTOXIC EFFECTS IN HUMANS AND LAB ANIMALS.
NIOSH; Criteria Document: Toluene
(1973) DHEW Pub. NIOSH 73-11023
USEPA; Ambient Water Quality Doc: Toluene (1980) EPA
440/5-80-075
NAS/NRC; The Alkyl Benzenes 384 pp (1981)
USEPA; Health Assessment Document: Toluene (1982)
EPA-800/8-82-008
TSCA CHIPs present a preliminary assessment of toluene's
potential for injury to human health & the environment (available at EPA's
TSCA Assistance Office: (202) 554-1404.
Environment Canada; Tech Info for Problem
Spills: Toluene (Draft) (1981)
Carlton WW et al; J Am Coll Toxicol 6 (1): 77-120 (1987). Final Report on the
Safety Assessment of Toluene.
DHHS/ATSDR; Toxicological Profile for Toluene (Update)
(1994) ATSDR/TP-93/14
DHHS/NTP; Toxicology & Carcinogenesis
Studies of Toluene in F344/N Rats and B6C3F1 Mice
Technical Report Series No. 371 (1990) NIH Publication No. 90-2826
Synonyms and Identifiers:
Synonyms:
ANTISAL 1A
**PEER REVIEWED**
BENZENE, METHYL-
**PEER REVIEWED**
Caswell no 859
**PEER REVIEWED**
CP 25
**PEER REVIEWED**
METHACIDE
**PEER REVIEWED**
METHANE, PHENYL-
**PEER REVIEWED**
METHYLBENZENE
**PEER REVIEWED**
METHYLBENZOL
**PEER REVIEWED**
NCI-C07272
**PEER REVIEWED**
PHENYLMETHANE
**PEER REVIEWED**
TOLUEEN (DUTCH)
**PEER REVIEWED**
TOLUEN (CZECH)
**PEER REVIEWED**
TOLUOL
**PEER REVIEWED**
TOLUOLO (ITALIAN)
**PEER REVIEWED**
Formulations/Preparations:
Research, reagent, nitration - all 99.8+%;
Industrial: Contains 94+%, with 5% xylene and small amounts of benzene and
nonaromatic hydrocarbons; 90/120: Less pure than industrial.
Grades: Research 99.99%; Pure 99.98%
Grades: 1st degree nitration; 2nd degree
commercial; 90% solvent
Grade: (Usually defined in terms of boiling
ranges) Pure, commercial, straw-colored, nitration, scintilation, industrial.
Shipping Name/ Number DOT/UN/NA/IMO:
UN 1294; Toluene
IMO 3.2; Toluene
Standard Transportation Number:
49 093 05; Toluene
49 093 56; Toluene (toluol),
reclaimed solvents, derived from the use of printing inks, consisting of 70%
recycled toluol and not more than 30% lactol spirits,
textile spirits and mineral spirits
49 060 10; Toluene (toluol),
mixed with aluminum alkyls, not to exceed 20% (aluminum alkyl)
EPA Hazardous Waste Number:
U220; A toxic waste when a discarded
commercial chemical product or manufacturing chemical intermediate or an
off-specification commercial chemical product or manufacturing chemical
intermediate.
F005; A hazardous waste from nonspecific
sources when a spent solvent.
RTECS Number:
NIOSH/XS5250000
Administrative Information:
Hazardous Substances Databank Number: 131
Last Revision Date: 20020118
Last Review Date: Reviewed by SRP on 1/29/2000
NYCAP
- Health Effects of Pesticides Speech
... that 'inert' does not mean biologically harmless; rather, inerts
include such things
as known human carcinogens like benzene and toluene ... Health Effects ...
http://www.crisny.org/not-for-profit/nycap/heps.htm
OSH
Answers: Health Effects of Toluene
... Health Effects of Toluene. ... by
aspiration. Back To Top. What are the
long term health effects of exposure to toluene? SKIN:
Repeated ...
http://www.ccohs.ca/oshanswers/chemicals/chem_profiles/toluene/health_tol.html
More Results From: www.ccohs.ca
Oregon
Department of Human Services HEALTH EFFECTS INFORMATION (PDF)
... Page 2. Technical Bulletin - Health Effects Information Toluene Page 2 TOLUENE
Toluene
is a volatile organic chemical used extensively in industry as a natural ...
http://www.ohd.hr.state.or.us/dwp/docs/fact/toluene.pdf
More Results From: www.ohd.hr.state.or.us
Inhalants
are breathable chemical vapors that produce ... (PDF)
... 2 Page 2. Facts on Inhalants / 2 HEALTH EFFECTS OF
INHALANTS Sniffing highly
concentrated amounts of chemicals can ... Many of these contain toluene.
...
http://www.bnl.gov/bnlweb/pubaf/pr/2002/docs/inhalants_fsheet.pdf
More Results From: www.bnl.gov
BEAM
... Toluene causes health affects from both short term
(acute less than 14 days) and
also long term (chronic greater ... The type and severity of health
effects ...
http://www.state.me.us/dep/air/beam/factsheets/toluene_fs.htm
More Results From: www.state.me.us
Eco-USA:
Toluene
... International Agency for Research on Cancer (IARC) and the Department
of Health and
Human Services (DHHS) have not classified toluene for carcinogenic effects.
...
http://www.eco-usa.net/toxics/toluene.html
More Results From: www.eco-usa.net
Isocyanates
... The EPA has prepared three Health Effects Fact Sheets
for specific isocyanates. Hexamethylene-1,6-diisocyanate
CAS No. ... Toluene 2,4-diisocyanate CAS No. ...
http://www.osha-slc.gov/SLTC/isocyanates/
More Results From: www.osha-slc.gov
DEP
- Drinking Water Program - Volatile Organic Chemical ...
... EPA has set the drinking water standard for toluene at 1 part
per million
(ppm) to protect against the risk of adverse health effects. ...
http://www.dep.state.fl.us/water/drinkingwater/vol_con.htm
More Results From: www.dep.state.fl.us
Adverse
Reproductive and Developmental Health Effects Where Used ...
(PDF)
... AP, CP, CW, IP Styrene H, MA, MI AP, CP, CW, IP, O (fire fighting) Toluene
... IP (banned
in US) Phthalates H, MI, SA, SBD CP, CF, CW, IP Key Health Effects
...
http://www.igc.org/psr/GBPSRPhysNat.pdf
More Results From: www.igc.org
toluene
recent reviews
... Teratogen Update Toluene. ... Long-term (gonadotropic,
embryotropic, mutagenic, ageing)
effects of ... Potential health effects of gasoline
and its constituents: A ...
http://cerhr.niehs.nih.gov/CERHRchems/toluene_reviews.htm
More Results From: cerhr.niehs.nih.gov
Cost/Benefit
Analysis of the Health and Environmental Issues of ... (PDF)
... Page 8. 8 Bren School of Environmental Science & Management, UCSB
Human Health
Effects of Toluene ? Acute and Chronic Toxicity at high levels ? ...
http://www-erd.llnl.gov/ethanol/proceed/fuelc_b.pdf
More Results From: www-erd.llnl.gov
NTN
ENVIRONMENTAL HEALTH DATA SEARCH - TOLUENE
... HEALTH EFFECTS: SHORT-TERM: Toluene is a fat
solvent that causes a CNS dysfunction
and the destruction of other tissues.(2) Inhalation of high vapour ...
http://www.oztoxics.org/ntn/tol.htm
More Results From: www.oztoxics.org
Health
Effects of Drinking Water Contaminants
... Some of the common VOCs are: benzene, trichloroethylene (TCE),
styrene, toluene,
and vinyl chloride. Possible chronic health effects include
cancer, central ...
http://www.ces.ncsu.edu/depts/fcs/housing/docs/fcs393.html
Chec-Ehome
... Source: Toluene, CASRN 108-88-3 (Human Health Effects).
... New York: McGraw-Hill,
1999. Toluene, CASRN 108-88-3 (Human Health Effects). ...
http://www.checnet.org/healthehouse/chemicals/chemicals-detail.asp?Main_ID=287
More Results From: www.checnet.org
Rw:
Incinerator Toxic Emissions: Human Health Effects
... Health effects of motor fuels: carcinogenicity of
gasoline--scientific ... Environ Health
Perspect. ... the lymphocytes of female workers exposed to benzene and toluene
...
http://www.rowatworks.com/Science/IncineratorToxic/
More Results From: www.rowatworks.com
Potential
health effects of exposure to volatile organic ...
... Analysis of BTEX compounds (benzene, toluene, ethylbenzene,
and xylenes mixed) was
performed in the ... The assessment of the potential health effects
of ...
http://www.fjokk.hu/cejoem/files/Volume5/Vol5No2/Ce992-07.htm
More Results From: www.fjokk.hu