• Evidence for Carcinogenicity
• Human Toxicity Excerpts
• Skin, Eye and Respiratory Irritations
• Medical Surveillance
• Populations at Special Risk
• Probable Routes of Human Exposure
• Body Burden
• Average Daily Intake
• Minimum Fatal Dose Level

• Emergency Medical Treatment
• Antidote and Emergency Treatment

• Evidence for Carcinogenicity
• Non-Human Toxicity Excerpts
• National Toxicology Program Studies
• Non-Human Toxicity Values
• Ecotoxicity Values
• TSCA Test Submissions

• Metabolism/Metabolites
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• Biological Half-Life
• Mechanism of Action
• Interactions

• Interactions
• Minimum Fatal Dose Level

• Environmental Fate/Exposure Summary
• Probable Routes of Human Exposure
• Body Burden
• Average Daily Intake
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• Environmental Water Concentrations
• Effluent Concentrations
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• FIFRA Requirements
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• Molecular Formula
• Molecular Weight
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• Density/Specific Gravity
• Heat of Combustion
• Heat of Vaporization
• Octanol/Water Partition Coefficient
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• DOT Emergency Guidelines
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• OSHA Standards
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TOLUENE
CASRN: 108-88-3
For other data, click on the Table of Contents

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).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 855 (1999)]**PEER REVIEWED**

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.
[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Toluene (108-88-3) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**PEER REVIEWED**

A4; Not classifiable as a human carcinogen.
[ American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2005, p. 56]**PEER REVIEWED**

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.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1573]**PEER REVIEWED**

... TOLUENE CAUSES DEFATTING OF SKIN WITH SUBSEQUENT DANGER OF DRYNESS, FISSURING AND SECONDARY INFECTION.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Volumes I and II. New York: McGraw-Hill Book Co., 1971., p. 1414]**PEER REVIEWED**

... SUDDEN DEATH AMONG "SNIFFERS" MAY BE ATTRIBUTED TO LETHAL CARDIAC ARRHYTHMIAS FOLLOWING SENSITIZATION OF THE MYOCARDIUM.
[Hamilton, A., and H. L. Hardy. Industrial Toxicology. 3rd ed. Acton, Mass.: Publishing Sciences Group, Inc., 1974., p. 276]**PEER REVIEWED**

... PERMANENT ENCEPHALOPATHY ... /IN/ MAN WHO INHALED TOLUENE REGULARLY FOR OVER 14 YR /WAS DESCRIBED/.
[American Conference of Governmental Industrial Hygienists. Documentation of the Threshold Limit Values and Biological Exposure Indices. 5th ed. Cincinnati, OH: American Conference of Governmental Industrial Hygienists, 1986., p. 578]**PEER REVIEWED**

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.
[Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 927]**PEER REVIEWED**

Metabolic acidosis with a high "anion gap" in 2 patients who had been sniffing toluene.
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 1455]**PEER REVIEWED**

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.
[Reynolds, J.E.F., Prasad, A.B. (eds.) Martindale-The Extra Pharmacopoeia. 28th ed. London: The Pharmaceutical Press, 1982., p. 1455]**PEER REVIEWED**

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 ...
[Clayton, G.D., F.E. Clayton (eds.) Patty's Industrial Hygiene and Toxicology. Volumes 2A, 2B, 2C, 2D, 2E, 2F: Toxicology. 4th ed. New York, NY: John Wiley & Sons Inc., 1993-1994., p. 1329]**PEER REVIEWED**

PERIPHERAL BLOOD LYMPHOCYTES FROM 32 MALE ROTOGRAVURE WORKERS SHOWED NO SIGNIFICANT DIFFERENCE FROM CONTROLS IN FREQUENCY OF CHROMOSOME ABERRATIONS & SISTER CHROMATID EXCHANGES.
[MAKI-PAAKKANEN J ET AL; J TOXICOL ENVIRON HEALTH 6: 775 (1980)]**PEER REVIEWED**

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.
[Fiscman CM, Oster JR; Am Med Assoc 241 (16): 1713-15 (1979) as cited in NRC; Alkyl Benzenes p.284 (1981)]**PEER REVIEWED**

Child of a mother with a 14 year history of solvent abuse showed symptoms of fetal alcohol syndrome.
[Toutant C, Lippman S; Lancet 1 (8130): 1356 (1979)]**PEER REVIEWED**

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.
[Ehyai A, Freemon FR; J Neural Neurosurg Psychiatry 46 (4): 349-51 (1983)]**PEER REVIEWED**

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. ...
[Benignus VA; Neurobehav Toxicol Teratol 3 (4): 407-15 (1981)]**PEER REVIEWED**

Lethal levels 1.0 mg%; 10.0 ug/ml
[Winek, C.L. Drug and Chemical Blood-Level Data 1985. Pittsburgh, PA: Allied Fischer Scientific, 1985., p. ]**PEER REVIEWED**

IN EXPERIMENTS IN VITRO, TOLUENE DID NOT CHANGE NUMBER OF SISTER-CHROMATID EXCHANGES OR THE NUMBER OF CHROMOSOMAL ABERRATIONS IN HUMAN LYMPHOCYTES.
[GERNER-SCMIDT P, FRIEDRICH U; MUTATION RESEARCH 58: 313 (1978)]**PEER REVIEWED**

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. ...
[Arai K et al; Brain Nerve Tokyo 38 (12): 1181-86 (1986)]**PEER REVIEWED**

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.
[Takeichi S et al; Forensic Sci Int 32 (2): 109-16 (1986)]**PEER REVIEWED**

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.
[Hanninen H et al; Int Arch Occupat Environ Health 59 (5): 475-83 (1987)]**PEER REVIEWED**

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.
[Cleland, J.G., G.L. Kingsbury. Multimedia Environmental Goals for Environmental Assessment. Volume 1. EPA-600/7-77-136a. Research Triangle Park, NC: EPA, Nov. 1977., p. E-146]**PEER REVIEWED**

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.
[U.S. Coast Guard, Department of Transportation. CHRIS - Hazardous Chemical Data. Volume II. Washington, D.C.: U.S. Government Printing Office, 1984-5., p. ]**PEER REVIEWED**

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.
[Sakata E et al; Pract Otal Kyoto 79 (12): 1999-2013 (1986)]**PEER REVIEWED**

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.
[Meulenbelt J et al; Br J Ind Med 47 (6): 417-20 (1990)]**PEER REVIEWED**

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.
[Stollery BT, Flindt MLH; Scand J Work, Environ, Health 14 (1): 45-8 (1988)]**PEER REVIEWED**

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.
[Boewer C et al; Int Arch Occup Environ Health 60 (3): 181-6 (1988)]**PEER REVIEWED**

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.
[Benignus VA; Neurotoxicol 2 (3): 567-88 (1981)]**PEER REVIEWED**

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.
[Hersh JH; J Med Genet 26 (5): 333-7 (1989)]**PEER REVIEWED**

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.
[Foo SC et al; BR J Ind Med 47 (7): 480-4 (1990)]**PEER REVIEWED**

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).
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995., p. 380]**PEER REVIEWED**

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.
[Klaassen, C.D., M.O. Amdur, Doull J. (eds.). Casarett and Doull's Toxicology. The Basic Science of Poisons. 5th ed. New York, NY: McGraw-Hill, 1995., p. 586]**PEER REVIEWED**

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/
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 1494]**PEER REVIEWED**

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.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 166]**PEER REVIEWED**

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.
[Ellenhorn, M.J., S. Schonwald, G. Ordog, J. Wasserberger. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins, 1997., p. 166]**PEER REVIEWED**

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.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V47 101 (1989)]**PEER REVIEWED**

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.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V47 101 (1989)]**PEER REVIEWED**

Humans exposed to concentrations of toluene of between 200-800 ppm may experience respiratory and ocular irritation.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1090]**PEER REVIEWED**

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.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1091]**PEER REVIEWED**

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.
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 1092]**PEER REVIEWED**

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/
[Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 724]**PEER REVIEWED**

Studies of women exposed to solvents such as benzene, toluene, and xylene have shown menstrual disturbances, principally associated with abnormal bleeding.
[Rom, W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 1992., p. 155]**PEER REVIEWED**

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.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1571]**PEER REVIEWED**

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.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1573]**PEER REVIEWED**

... 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.
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1574]**PEER REVIEWED**

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).
[American Conference of Governmental Industrial Hygienists, Inc. Documentation of the Threshold Limit Values and Biological Exposure Indices. 6th ed. Volumes I, II, III. Cincinnati, OH: ACGIH, 1991., p. 1575]**PEER REVIEWED**

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).
[Meulenbelt J et al; Br J Ind Med 47: 417-20 (1990) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.31 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

Severe renal tubular acidosis was observed in five pregnant women who were chronic abusers of paints containing toluene.
[Goodwin TM; Obstet Gynecol 71: 715-18 (1988) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.36 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Echeverria D et al; Br J Ind Med 48: 750-61 (1991) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.40 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Yin S et al; Ind Health 25: 113-30 (1987) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.41 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Lindemann R; Acta Pediatr Scand 80: 882-4 (1991) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.49 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 845 (1999)]**PEER REVIEWED**

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.
[Erramouspe J et al; J Psychoactive Drugs 28 (2): 201-4 (1996)]**PEER REVIEWED**

Skin, Eye and Respiratory Irritations:

A human eye irritant. An experimental skin and severe eye irritant.
[Lewis, R.J. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 3190]**PEER REVIEWED**

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.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 526]**PEER REVIEWED**

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.
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 2185]**PEER REVIEWED**

Hippuric acid levels above 5 g/l of urine may result from exposure greater than 200 ppm determined as a time weighted average.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 870]**PEER REVIEWED**

Populations at Special Risk:

Preclude individuals from exposure to toluene who have central nervous system or liver diseases.
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 526]**PEER REVIEWED**

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).
[(1) NIOSH; National Occupational Exposure Survey (NOES) (1983)]**PEER REVIEWED**

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).
[(1) Hollund BE, Moen BE; Ann Occup Hyg 42: 277-81 (1998) (2) Eitzer BD; Environ Sci Technol 29: 896-902 (1995) (3) Brandorff NP et al; Occup Environ Med 52: 454-63 (1995) (4) Angerer J, Kraemer A; Int Arch Occup Environ Health 69: 91-96 (1997)]**PEER REVIEWED**

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).
[(1) Pellizzari ED et al; Bull Environ Contam Toxicol 28: 322-8 (1982) (2) Antoine SR et al; Bull Environ Contam Toxicol 36: 364-71 (1986) (3) Stanley JS; Broad Scan Analysis of the FY82 National Human Adipose Tissue Survey Specimens Vol. I Executive Summary p. 5 USEPA-560/5-86-035 (1986) (4) Lindstrom AB, Pleil J; J Air Waste Manage Assoc 46: 676-82 (1996) (5) Ashley DL et al; Clin Chem 40: 1401-14 (1994) (6) Angerer J, Kraemer A; Int Arch Occup Environ Health 69: 91-96 (1997)]**PEER REVIEWED**

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.
[(1) Brodzinsky R, Singh HB; Volatile Organics in the Atmosphere and Assessment of available data: p. 126-7 SRI Contract 68-02-3459 (1982) (2) Otson R et al; J Assoc Off Analyt Chem 65: 1370-4 (1982)]**PEER REVIEWED**

Minimum Fatal Dose Level:

Ingestion of approximately 60 ml (625 mg/kg) of toluene proved fatal for a while male mental patient.
[Ameno K et al; Forensic Sci Int 41: 255-60 (1989) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.52 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

Emergency Medical Treatment:

Emergency Medical Treatment:

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/
[Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 181-2]**PEER REVIEWED**

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/
[Bronstein, A.C., P.L. Currance; Emergency Care for Hazardous Materials Exposure. 2nd ed. St. Louis, MO. Mosby Lifeline. 1994., p. 182]**PEER REVIEWED**

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).
[IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work)., p. V71 855 (1999)]**PEER REVIEWED**

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.
[U.S. Environmental Protection Agency's Integrated Risk Information System (IRIS) on Toluene (108-88-3) Available from: http://www.epa.gov/ngispgm3/iris on the Substance File List as of March 15, 2000]**PEER REVIEWED**

A4; Not classifiable as a human carcinogen.
[ American Conference of Governmental Industrial Hygienists TLVs and BEIs. Threshold Limit Values for Chemical Substances and Physical Agents and Biological Exposure Indices. Cincinnati, OH, 2005, p. 56]**PEER REVIEWED**

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.
[Clarke, M. L., D. G. Harvey and D. J. Humphreys. Veterinary Toxicology. 2nd ed. London: Bailliere Tindall, 1981., p. 100]**PEER REVIEWED**

... /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 ...
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 70]**PEER REVIEWED**

... SWELLING O