Toluene Sources, Testing, Air Purification, and Health Information

• 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
• Absorption, Distribution & Excretion
• 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
• Natural Pollution Sources
• Artificial Pollution Sources
• Environmental Fate
• Environmental Biodegradation
• Environmental Abiotic Degradation
• Environmental Bioconcentration
• Soil Adsorption/Mobility
• Volatilization from Water/Soil
• Environmental Water Concentrations
• Effluent Concentrations
• Sediment/Soil Concentrations
• Atmospheric Concentrations
• Food Survey Values
• Plant Concentrations
• Fish/Seafood Concentrations
• Milk Concentrations
• Other Environmental Concentrations

• FIFRA Requirements
• TSCA Requirements
• CERCLA Reportable Quantities
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• Federal Drinking Water Standards
• Federal Drinking Water Guidelines
• State Drinking Water Standards
• State Drinking Water Guidelines
• FDA Requirements
• Allowable Tolerances

• Molecular Formula
• Molecular Weight
• Color/Form
• Odor
• Boiling Point
• Melting Point
• Corrosivity
• Critical Temperature & Pressure
• Density/Specific Gravity
• Heat of Combustion
• Heat of Vaporization
• Octanol/Water Partition Coefficient
• Solubilities
• Spectral Properties
• Surface Tension
• Vapor Density
• Vapor Pressure
• Viscosity
• Other Chemical/Physical Properties

• DOT Emergency Guidelines
• Odor Threshold
• Skin, Eye and Respiratory Irritations
• Fire Potential
• NFPA Hazard Classification
• Flammable Limits
• Flash Point
• Autoignition Temperature
• Fire Fighting Procedures
• Toxic Combustion Products
• Firefighting Hazards
• Explosive Limits & Potential
• Hazardous Reactivities & Incompatibilities
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• Prior History of Accidents
• Immediately Dangerous to Life or Health
• Protective Equipment & Clothing
• Preventive Measures
• Shipment Methods and Regulations
• Storage Conditions
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• OSHA Standards
• Threshold Limit Values
• NIOSH Recommendations
• Immediately Dangerous to Life or Health
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• Methods of Manufacturing
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• Clinical Laboratory Methods
• Analytic Laboratory Methods
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• Special Reports

• Synonyms
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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 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.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 72]**PEER REVIEWED**

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.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 71]**PEER REVIEWED**

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/
[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. 1327]**PEER REVIEWED**

INTRATRACHEAL ADMIN /TO CATS/ WITH CHRONICALLY IMPLANTED ELECTRODES INDUCED SEIZURES ALONG WITH BEHAVIORAL DISTURBANCES SUCH AS NODDING, TWITCHING & APPARENT HALLUCINATIONS.
[CONTRERAS CM ET AL; ELECTROENCEPHALOGR CLIN NEUROPHYSIOL 46 (3): 290 (1979)]**PEER REVIEWED**

... 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.
[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 1438]**PEER REVIEWED**

/GAVAGING/ MICE /WITH/ 1.0 MG/KG ON DAYS 6 THROUGH 15 /OF GESTATION/ ... INCR CLEFT PALATE IN THE OFF-SPRING.
[Shepard, T.H. Catalog of Teratogenic Agents. 5th ed. Baltimore, MD: The Johns Hopkins University Press, 1986., p. 1438]**PEER REVIEWED**

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.
[BOS RP ET AL; MUTAT RES 88: 273 (1981)]**PEER REVIEWED**

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.
[CHAND P, CLAUSEN J; BULL ENVIRON CONTAM TOXICOL 28 (5): 542 (1982)]**PEER REVIEWED**

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.
[PAKSY KA ET AL; ACTA PHYSIOL ACAD SCI HUNG 59 (4): 317 (1982)]**PEER REVIEWED**

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.
[HONMA T; TOXICOL LETT 16 (1-2): 17 (1983)]**PEER REVIEWED**

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.
[USEPA; Ambient Water Quality Criteria Doc: Toluene p.C-26 (1980) EPA 440/5-80-075]**PEER REVIEWED**

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.
[USEPA; Ambient Water Quality Criteria Doc: Toluene p.14-6 (1980) EPA 440/5-80-075]**PEER REVIEWED**

... 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.
[Pryor GT et al; Neurobehav Toxicol Terat 5 (1): 53-7 (1983)]**PEER REVIEWED**

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.
[Courtney KD et al; Fundam Appl Toxicol 6: 145-54 (1986)]**PEER REVIEWED**

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.
[Glowa JR et al; J Environ Pathol Toxicol Oncol 6 (5-6): 153-68 (1986)]**PEER REVIEWED**

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.
[Naalsund LU; Acta Pharmacol Toxicol 59 (4): 325-31 (1988)]**PEER REVIEWED**

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.
[Kyrklund T et al; Toxicology 45: 123-33 (1987)]**PEER REVIEWED**

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.
[Slomianka L et al; Toxicol 62 (2): 189-202 (1990)]**PEER REVIEWED**

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.
[Silva V AD et al; Toxicol 64 (2): 155-68 (1990)]**PEER REVIEWED**

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.
[DHHS/NTP; Toxicology and Carcinogenesis Studies of Chlorobenzene in F344/N Rats and B6C3F1 Mice (Inihalation Studies) p.4 (1990) Technical Rpt Series No. 371 NIH Pub No. 90-2826]**PEER REVIEWED**

... Toluene can alter learned behavior at concentrations below anesthetic levels but, in general, above 1000 ppm.
[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. 747]**PEER REVIEWED**

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.
[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 96 (1989)]**PEER REVIEWED**

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.
[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 98 (1989)]**PEER REVIEWED**

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.
[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 99 (1989)]**PEER REVIEWED**

Animal studies in mice exposed to toluene at concentrations of 2.5-500 ppm demonstrated decreased host defense to respiratory infections.
[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**

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.
[Ikeda N et al; Forensic Sci Intern 44: 151-8 (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**

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.
[Aranyi C et al; Toxicol Lett 25: 103-10 (1985) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.39 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Pryor GT, Rebert CS; Neurotoxicology 13: 225-34 (1992) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.44 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Lorenzana-Jimenez M, Salas M; Neurotoxicol Teratol 12: 353-7 (1990) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.45 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Wood RW et al; Toxicol Appl Pharmacol 68: 462-72 (1983) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.45 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Castilla-Serna L et al; Arch Invest Med 22: 295-301 (1991) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.46 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Arito H et al; Arch Toxicol 62: 76-80 (1988) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.46 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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. ...
[U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.61 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Lataye R et al; Neurotoxicol Teratol 21 (3): 267-76 (1999)]**PEER REVIEWED**

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.
[DHHS/NTP; Toxicology and Carcinogenesis Studies of Chlorobenzene in F344/N Rats and B6C3F1 Mice (Inhalation Studies) p.4 (1990) Technical Rpt Series No. 371 NIH Pub No. 90-2826]**PEER REVIEWED**

Non-Human Toxicity Values:

LD50 Rat oral 2.6 to 7.5 g/kg
[DHHS/NTP; Toxicology and Carcinogenesis Studies of Chlorobenzene in F344/N Rats and B6C3F1 Mice (Gavage Studies) p.16 (1990) Technical Rpt Series No. 371 NIH Pub No. 90-2826]**PEER REVIEWED**

LD50 Rabbit dermal 14.1 ml/kg
[DHHS/NTP; Toxicology and Carcinogenesis Studies of Chlorobenzene in F344/N Rats and B6C3F1 Mice (Gavage Studies) p.16 (1990) Technical Rpt Series No. 371 NIH Pub No. 90-2826]**PEER REVIEWED**

LD50 Rat (female) ip 1.64 g/kg
[DHHS/NTP; Toxicology and Carcinogenesis Studies of Chlorobenzene in F344/N Rats and B6C3F1Mice (Inhalation Studies) p.16 (1990) Technical Rpt Series No. 371 NIH Pub No. 90-2826]**PEER REVIEWED**

LD50 MOUSE IP 1.15 G/KG
[KOGA K, OHMIYA Y; J TOXICOL SCI 3 (1): 25 (1978)]**PEER REVIEWED**

LD50 Rat oral 5000 mg/kg
[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**

LD50 Rat ip 1332 mg/kg
[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**

LD50 Rat iv 1960 mg/kg
[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**

LC50 Mouse ihl 400 ppm/24 hr
[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**

LD50 Mouse ip 59 mg/kg
[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**

LD50 Mouse sc 2250 mg/kg
[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**

LD50 Mouse ip 640 mg/kg
[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**

LD50 Rabbit skin 12,124 mg/kg
[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**

... The LC50 for toluene in mice is 5320 ppm/8 hr /via inhalation/ ...
[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. 746]**PEER REVIEWED**

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.
[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. 1568]**PEER REVIEWED**

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/
[BUCCAFUSCO RJ ET AL; BULL ENVIRONM CONTAM TOXICOL 26 (4): 446-52 (1981)]**PEER REVIEWED**

LC50 Palaemonetes pugio (grass shrimp) 9.5 mg/l/96 hr /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1727]**PEER REVIEWED**

LC50 Cancer magister (crab larvae stage I) 28 mg/l/96 hr /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1727]**PEER REVIEWED**

LC50 Crangon franciscorum (shrimp) 4.3 mg/l/96 hr /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1728]**PEER REVIEWED**

LC50 Pimephales promelas (fathead minnow) 56-34 mg/l/24-96 hr /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1728]**PEER REVIEWED**

LC50 Lebistes reticulatus (guppy) 63-59 mg/l/24-96 hr /Conditions of bioassay not specified/
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1729]**PEER REVIEWED**

LC50 Channel catfish 240 mg/l 96 hr /Conditions of bioassay not specified/
[Environment Canada; Tech Info for Problem Spills: Toluene p.71-75 (1981)]**PEER REVIEWED**

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/
[Pickering QH, Henderson C; J Water Pollution Control Fed 38: 1419-1429 (1966) as cited in NRC; Alkyl Benzenes p.352 (1981)]**PEER REVIEWED**

LC50 Carassius auratus (goldfish) 57.68 mg/l 96 hr (95% Confidence Limits= 48.87-68.75 mg/l) /Conditions of bioassay not specified/
[Pickering QH, Henderson C; J Water Pollution Control Fed 38: 1419-1429 (1966) as cited in NRC; Alkyl Benzenes p.352 (1981)]**PEER REVIEWED**

LC50 Lebistes reticulatus (guppy) 59.30 mg/l 96 hr (95% Confidence Limits= 50.87-70.34 mg/l) /Conditions of bioassay not specified/
[Pickering QH, Henderson C; J Water Pollution Control Fed 38: 1419-1429 (1966) as cited in NRC; Alkyl Benzenes p.352 (1981)]**PEER REVIEWED**

LC50 Daphnia magna, (water flea) 313 mg/l 48 hr /Conditions of bioassay not specified/
[USEPA. In Depth Studies on Health and Environ Impact of Sel Water Poll (1978) EPA 68-01-4646 as cited in NRC; Alkyl Benzenes p.356 (1981)]**PEER REVIEWED**

LC50 Nitocra spinipes (copepod) 24.2-74.2 mg/l 24 hr /Conditions of bioassay not specified/
[Potera GT; Effects of Benzene, Toluene, and Ethylbenzene on Several Important Members of the Estuarine Ecosystem Ph.D. Dissertation p.1-117 (1975) as cited in NRC; Alkyl Benzenes p.355 (1981)]**PEER REVIEWED**

LC50 Artemia salina (brine shrimp) 33 mg/l 24 hr /Conditions of bioassay not specified/
[Price KS et al; J Water Pollut Control Fed 46: 63-77 (1974) as cited in NRC; Alkyl Benzenes p.355 (1981)]**PEER REVIEWED**

LC50 Morone saxatilis (striped bass) 7.3 mg/l 96 hr /Conditions of bioassay not specified/
[Benville PE, Korn S; Calif Fish Game 63: 204-209 (1977) as cited in NRC; Alkyl Benzenes p.353 (1981)]**PEER REVIEWED**

LC50 Cyprinodon variegatus (sheepshead minnow) 277-485 mg/l 96 hr /Conditions of bioassay not specified/
[NRC; Alkyl Benzenes p.354 (1981)]**PEER REVIEWED**

LC50 Aedes aegypti-4th instar (mosquito larvae) 22 mg/l /Conditions of bioassay not specified/
[USEPA. In Depth Studies on Health Environ Impact of Sel Water Pollutants (1978) EPA 68-01-4646 as cited in NRC; Alkyl Benzenes p.362 (1981)]**PEER REVIEWED**

LC50 Calandra granaria (grain weevil) 210 mg/l /in air/
[Ferguson J, Pirie H; Ann Appl Biol 35:532-550 (1948) as cited in NRC; Alkyl Benzenes p 362 (1981)]**PEER REVIEWED**

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/
[Devlin EW et al; Bull Environ Contam Toxicol 29 (1): 12-17 (1982)]**PEER REVIEWED**

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.
[Geiger D.L., Poirier S.H., Brooke L.T., Call D.J., eds. Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales Promelas). Vol. III. Superior, Wisconsin: University of Wisconsin-Superior, 1986., p. 163]**PEER REVIEWED**

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.
[Geiger D.L., Poirier S.H., Brooke L.T., Call D.J., eds. Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales Promelas). Vol. III. Superior, Wisconsin: University of Wisconsin-Superior, 1986., p. 163]**PEER REVIEWED**

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.
[American Petroleum Inst.; Effects of Toluene Exposure on Auditory Pathways, Final Report. (1979), EPA Document No. 40-8450019, Fiche No. OTS0507495]**UNREVIEWED**

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.
[American Petroleum Institute; 26 Week Inhalation Toxicity Study in the Rat (1980), EPA Document No. FYI-AX-1081-0136, Fiche No. 0136-0]**UNREVIEWED**

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.
[Litton Bionetics, Inc.; Teratology Study in Rats, Toluene, Final Report (1978), EPA Document No. 87-8210353, Fiche No. OTS0205936]**UNREVIEWED**

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.
[Litton Bionetics, Inc.; Mutagenicity Evaluation of Toluene. (1978), EPA Document No. 878210352, Fiche No. OTS0205936]**UNREVIEWED**

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.
[Litton Bionetics, Inc.; Mutagenicity Evaluation of Toluene. (1978), EPA Document No. 878210352, Fiche No. OTS0205936]**UNREVIEWED**

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.
[Litton Bionetics, Inc.; Mutagenicity Evaluation of Toluene, Mouse Dominant Lethal Assay, Final Report. (1981), EPA Document No. FYI-AX-1081-0136, Fiche No. OTS0000136-0 ]**UNREVIEWED**

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.
[Litton Bionetics, Inc.; Mutagenicity Evaluation of Toluene. (1978), EPA Document No. 878210352, Fiche No. OTS0205936 ]**UNREVIEWED**

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.
[Thomas J. Franz M.D.; Absorption of Petroleum Products Across the Skin of Man and Monkey, Draft Report, (no date), EPA Document No. FYI-AX-0187-0185, Fiche No. OTS0000185-4 ]**UNREVIEWED**

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.
[Haddad, L.M., Clinical Management of Poisoning and Drug Overdose. 2nd ed. Philadelphia, PA: W.B. Saunders Co., 1990., p. 1224]**PEER REVIEWED**

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.
[ANGERER J; INT ARCH OCCUP ENVIRON HEALTH 43 (1): 63 (1979)]**PEER REVIEWED**

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.
[Bakke OM, Scheline RR; Tox Appl Pharm 16: 691-700 (1970) as cited in NRC; Alkyl Benzenes p.221 (1981)]**PEER REVIEWED**

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.
[James MO et al; Proc R Soc Lond Ser B 182: 25-35 (1972) as cited in NRC; Alkyl Benzenes p.219 (1981)]**PEER REVIEWED**

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.
[Nise G et al; Br J Ind Med 46 (6): 407-11 (1989)]**PEER REVIEWED**

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.
[Inoue O et al; Bull Environ Contam Toxicol 43 (1): 74-9 (1989)]**PEER REVIEWED**

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.
[Inoue O et al; Int Arch Occup Environ Health 60 (1): 15-20 (1988)]**PEER REVIEWED**

Absorption, Distribution & Excretion:

TOLUENE VAPOR IS READILY ABSORBED BY INHALATION AND THE LIQUID BY THE GI TRACT, BUT POORLY FROM THE SKIN.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 68]**PEER REVIEWED**

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).
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 69]**PEER REVIEWED**

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).
[Doull, J., C.D. Klaassen, and M. D. Amdur (eds.). Casarett and Doull's Toxicology. 2nd ed. New York: Macmillan Publishing Co., 1980., p. 489]**PEER REVIEWED**

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.
[VEULEMAN H ET AL; INT ARCH OCCUP ENVIRON HEALTH 42 (2): 105 (1978)]**PEER REVIEWED**

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.
[KOGA K; FOLIA PHARMACOL JPN 74 (6): 687 (1978)]**PEER REVIEWED**

The blood/gas partition coefficient ranges from 12.4 to 15.6.
[NRC; Alkyl Benzenes p.220 (1981)]**PEER REVIEWED**

At equilibrium, the avg toluene concn per liter of blood is 2.4 mg for each 100 ppm toluene in the envir air.
[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**

... Whole body autoradiography has been modified and applied to distribution studies of ... toluene. ...
[Bergman K; CRC Crit Review Toxicol 12 (1): 59-118 (1983)]**PEER REVIEWED**

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.
[Baelum J et al; Int Arch Occup Environ Health 59 (3): 281-94 (1987)]**PEER REVIEWED**

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.
[Ghantous H, Danielson BRG; Biol Res Pregnancy Perinatol 7 (3): 98-105 (1986)]**PEER REVIEWED**

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.
[Sullivan MJ, Conolly RB; Environ Research 45 (1): 64-70 (1988)]**PEER REVIEWED**

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.
[Pezzagno G et al; Am Ind Hygiene Assoc J 49 (11): 546-52 (1988)]**PEER REVIEWED**

Animal studies indicate that toluene readily crosses the placenta.
[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**

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.
[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 93 (1989)]**PEER REVIEWED**

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.
[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 93 (1989)]**PEER REVIEWED**

When rabbits were given a single oral dose of 350 mg/kg bw toluene, 19% was exhaled unchanged within 12 hr.
[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 94 91989)]**PEER REVIEWED**

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.
[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 94 (1989)]**PEER REVIEWED**

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.
[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**

The uptake of toluene in the blood is doubled during physical activity compared to the uptake at rest.
[Zenz, C., O.B. Dickerson, E.P. Horvath. Occupational Medicine. 3rd ed. St. Louis, MO., 1994, p. 723]**PEER REVIEWED**

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.
[Tsuruta H; Ind Health 27: 37-47 (1989) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.68 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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.
[Lam CW et al; Toxicol Appl Pharmacol 104: 117-29 (1990) as cited in U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.68 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

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).
[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.71 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

Biological Half-Life:

0.083 days (Inhaled as environmental air)
[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**

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. ...
[Fuxe K et al; Toxicol Lett 12 (2-3): 115-23 (1982)]**PEER REVIEWED**

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.
[Bjornaes S, Naalsund Lu; Toxicol 49 (2-3): 367-74 (1988)]**PEER REVIEWED**

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.
[Mickiewicz W, Rzeczycki W; Biochem Pharmacol 37 (23): 4439-44 (1988)]**PEER REVIEWED**

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.
[KOGA K, OHMIYA Y; J TOXICOL SCI 3 (1): 25 (1978)]**PEER REVIEWED**

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.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3289]**PEER REVIEWED**

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.
[TOFTGARD R ET AL; ACTA PHARMACOL TOXICOL 51 (2): 108 (1982)]**PEER REVIEWED**

Perchloroethylene enhances toxicity of toluene admin orally in rats.
[USEPA; Health Assessment Document: Toluene p.15-1 (1982) EPA-800/8-82-008]**PEER REVIEWED**

Toluene and trichloroethylene seem to exhibit competitive inhibition.
[Ikeda M; Int Arch Arbeitsmed 33 (2): 125 (1974)]**PEER REVIEWED**

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.
[Ungvary G et al; Teratology 27 (2): 261-9 (1983)]**PEER REVIEWED**

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.
[Takahashi S et al; Arch Toxicol 59 (5): 307-10 (1987)]**PEER REVIEWED**

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 toluene was observed.
[Iregren A et al; Scand J Work Environ Health 12: 128-36 (1986)]**PEER REVIEWED**

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.
[Chakrabarti S, Tuchweber B; Toxicol Lett 39 (1): 27-34 (1987)]**PEER REVIEWED**

... Toluene has been shown to be a competitive inhibitor of the metabolism of benzene. This competitive interaction alleviates the metabolite-mediated toxicity of benzene ...
[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. 741]**PEER REVIEWED**

Xenobiotic competitors for the same metabolic route, such as benzene and xylene, would ... have an impact on toluene metabolism.
[U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.95 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

... A single alcoholic drink has a very strong, acute inhibitory effect on the hepatic elimination of toluene.
[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 842 (1999)]**PEER REVIEWED**

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.
[Ernstgard L et al; Toxicol Sci 48 (2): 189-96 (1999)]**PEER REVIEWED**

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.
[KOGA K, OHMIYA Y; J TOXICOL SCI 3 (1): 25 (1978)]**PEER REVIEWED**

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.
[Clayton, G. D. and F. E. Clayton (eds.). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons, 1981-1982., p. 3289]**PEER REVIEWED**

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.
[TOFTGARD R ET AL; ACTA PHARMACOL TOXICOL 51 (2): 108 (1982)]**PEER REVIEWED**

Perchloroethylene enhances toxicity of toluene admin orally in rats.
[USEPA; Health Assessment Document: Toluene p.15-1 (1982) EPA-800/8-82-008]**PEER REVIEWED**

Toluene and trichloroethylene seem to exhibit competitive inhibition.
[Ikeda M; Int Arch Arbeitsmed 33 (2): 125 (1974)]**PEER REVIEWED**

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.
[Ungvary G et al; Teratology 27 (2): 261-9 (1983)]**PEER REVIEWED**

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.
[Takahashi S et al; Arch Toxicol 59 (5): 307-10 (1987)]**PEER REVIEWED**

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 toluene was observed.
[Iregren A et al; Scand J Work Environ Health 12: 128-36 (1986)]**PEER REVIEWED**

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.
[Chakrabarti S, Tuchweber B; Toxicol Lett 39 (1): 27-34 (1987)]**PEER REVIEWED**

... Toluene has been shown to be a competitive inhibitor of the metabolism of benzene. This competitive interaction alleviates the metabolite-mediated toxicity of benzene ...
[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. 741]**PEER REVIEWED**

Xenobiotic competitors for the same metabolic route, such as benzene and xylene, would ... have an impact on toluene metabolism.
[U.S. Dept Health & Human Services/Agency for Toxic Substances & Disease Registry; Toxicological Profile for Toluene (Update) p.95 (1994) ATSDR/TP-93/14]**PEER REVIEWED**

... A single alcoholic drink has a very strong, acute inhibitory effect on the hepatic elimination of toluene.
[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 842 (1999)]**PEER REVIEWED**

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.
[Ernstgard L et al; Toxicol Sci 48 (2): 189-96 (1999)]**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**

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)
**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**

Natural Pollution Sources:

Toluene occurs in nature in ... natural gas deposits ...
[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 82 (1989)]**PEER REVIEWED**

Toluene has been detected in emissions from volcanos, forest fires and crude oil(1).
[(1) Graedel TE; Chemical Compounds in the Atmosphere, NY, NY, Academic Press p. 108 (1978)]**PEER REVIEWED**

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/
[Rom, W.N. (ed.). Environmental and Occupational Medicine. 2nd ed. Boston, MA: Little, Brown and Company, 1992., p. 1212]**PEER REVIEWED**

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).
[(1) Graedel TE; Chemical Compounds in the Atmosphere. NY, NY: Academic Press p. 108 (1978) (2) Walker P; Air Pollution Assessment of Toluene. TR-7215 Mitre Corp, McLean VA, pp. 1-22, 46-92 (1976) (3) Budvari S; Merck Index, 12th ed, Whitehouse Station, NJ Merck & Co. p 1626 (1996)]**PEER REVIEWED**

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).
[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Wilson JT et al; J Environ Qual 10: 501-6 (1981) (3) Nathwani JS, Phillips CR; Chemosphere 6: 157-62 (1977) (4) Mackay D et al; Environ Sci Technol 13: 333-36 (1979) (5) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation Washington, DC: Taylor and Francis (1989) (6) Allen-King RM et al; Environ Toxicol Chem 13: 693-705 (1994) (7) Aronson D et al; Aerobic biodegradation of organic chemicals in environmental media: a summary of field and laboratory studies. USEPA (1999)]**PEER REVIEWED**

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).
[(1) Swann RL et al; Res Rev 85: 17-28 (1983) (2) Kan AT et al; Environ Sci Technol 32: 892-902 (1998) (3) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 4-9, 15-1 to 15-29 (1990) (4) Mackay D et al; Environ Sci Technol 13: 333-36 (1979) (5) Franke C et al; Chemosphere 29: 1501- 14 (1994) (6) Ogata M, Miyake Y; Water Res 12: 1041-4 (1978) (7) Freitag D et al; Chemsophere 14: 1589-1616 (1985) (8) Capel PD, Larson SL; Chemosphere 30: 1097-1107 (1995)]**PEER REVIEWED**

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).
[(1) Bidleman TF; Environ Sci Technol 22: 361-367 (1988) (2) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation Washington, DC: Taylor and Francis (1989)(3) Atkinson R; J Phys Chem Ref Data Monograph 2 (1994)]**PEER REVIEWED**

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).
[(1) Tabak HH et al; J Water Pollut Control Fed 53: 1503-8 (1981) (2) Davis EM et al; Water Res 15: 1125-7 (1981) (3) Bridie AL et al; Water Res 13: 627-30 (1979) (4) Kawasaki M; Ecotox Environ Safety 4: 444-54 (1980) (5) Malaney GW, McKinney RE; Water Sewage Works 113: 302-9 (1966) (6) Price KS et al; J Water Pollut Control Fed 46: 63-77 (1974) (7) Matsui S et al; Prog Water Technol 7: 645-59 (1975) (8) Van der Linden AC; Dev Biodegrad Hydrocarbons 1: 165-200 (1978) (9) Button DK et al; Appl Environ Microbiol 42: 708-19 (1981) (10) Lee RF; 1977 Oil Spill Conf Amer Petrol Inst p 611-6 (1977) (11) Reichardt PB et al; Environ Sci Technol 15: 75-9 (1981) (12) Wakeham SG et al; Environ Sci Technol 17: 611-7 (1983) (13) Grbic-Galic D, Vogel TM; Appl Environ Microbiol 53: 254-60 (1987)]**PEER REVIEWED**

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).
[(1) Kappeler T, Wuhrmann K; Water Res 12: 327-33 (1978) (2) Wilson JT et al; Devel Indust Microbiol 24: 225-33 (1983) (3) McNabb JF et al; 81st Ann Mtg Amer Soc Microbiology p.213 (1981) (4) Fewson CA; FEMS Symp 12 (Microb Deg Xenobiotics Recalcitrant Cmpds): 141-79 (1981) (5) Wilson JT et al; Ground Water 21: 134-42 (1983)]**PEER REVIEWED**

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).
[(1) Allen-King RM et al; Environ Toxicol Chem 13: 693-705 (1994) (2) Allen-King RM et al; J Environ Qual 25: 287-95 (1996) (3) Borden RC et al; Water Resour Res 33: 1105-15 (1997) (4) Borden RC et al; Anaerobic Biodegradation of BTEX in Aquifer Material USEPA/600/S-97/003. National Risk Management Laboratory, Ada, OK. pp. 9 (1997) (5) Alvarez PJJ, Vogel TM; Appl Environ Microbiol 57: 2981-85 (1991) (6) Capel PD, Larson SL; Chemosphere 30: 1097-1107 (1995) (7) Aronson D et al; Aerobic biodegradation of organic chemicals in environmental media: a summary of field and laboratory studies. USEPA (1999)]**PEER REVIEWED**

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.
[(1) Atkinson R; J Phys Chem Ref Data Monograph 2 (1994) (2) Atkinson R et al; Atmos Environ 24: 2647-54 (1990) (3) Atkinson R, Carter WPL; Chem Rev 84: 437-70 (1984) (4) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 7-4, 7-5 (1990)]**PEER REVIEWED**

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.
[(1) Ogata M, Miyake Y; Water Res 12: 1041-4 (1978) (2) Freitag D et al; Chemosphere 14: 1589-1616 (1985) (3) Franke C et al; Chemosphere 29: 1501-14 (1994)]**PEER REVIEWED**

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.
[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 90 (1989)]**PEER REVIEWED**

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.
[(1) Wilson JT et al; J Environ Qual 10: 501-6 (1981) (2) Nathwani JS, Phillips CR; Chemosphere 6: 157-62 (1977) (3) Kan AT et al; Environ Sci Technol 32: 892-902 (1998) (4) Swann RL et al; Res Rev 85: 17-28 (1983)]**PEER REVIEWED**

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).
[(1) Mackay D et al; Environ Sci Technol 13: 333-36 (1979) (2) Lyman WJ et al; Handbook of Chemical Property Estimation Methods. Washington, DC: Amer Chem Soc pp. 15-1 to 15-29 (1990) (3) Daubert TE, Danner RP; Physical and Thermodynamic Properties of Pure Chemicals Data Compilation Washington, DC: Taylor and Francis (1989)]**PEER REVIEWED**

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/
[Sullivan, J.B. Jr., G.R. Krieger (eds.). Hazardous Materials Toxicology-Clinical Principles of Environmental Health. Baltimore, MD: Williams and Wilkins, 1992., p. 304]**PEER REVIEWED**

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).
[(1) Burmaster DE; Environ 24: 6-13, 33-6 (1982) (2) Tester DJ, Harker RJ; Water Pollut Control 80: 614-31 (1981) (3) Hutchins SR et al; Environ Toxicol Chem 2: 195-216 (1983) (4) Stuermer DH et al; Environ Sci Technol 16: 582-7 (1982) (5) Rich CA; Stud Environ Sci 17(Qual Groundwater): 309-14 (1981) (6) Coturvo JA; Sci Total Environ 47: 7-26 (1985)]**PEER REVIEWED**

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).
[(1) Otson R et al; J Assoc Off Analyt Chem 65: 1370-4 (1982) (2) Williams DT et al; Chemosphere 11: 263-76 (1982) (3) NAS; The Alkyl Benzene USEPA Contract No. 68-02-4655 (1980) (4) Dyksen JE, Hess AF III: J Amer Water Works Assoc 74: 394-403 (1982) (5) Keith LH et al; pp. 329-73 in Identification and analysis of organic pollutants in Water, Keith LH, ed, Ann Arbor Sci Publ (1976) (6) Bedding ND et al; Sci Total Environ 25: 143-67 (1982) (7) Piet GJ, Morra CF; pp. 31-42 in Artificial Groundwater Recharge (Water Res Eng Ser) Huisman L, Olsthorn TN, eds, Pitman Publ (1983) (8) Burmaster DE; Environ 24: 6-13, 33-6 (1982) (9) Tester DJ, Harker RJ; Water Pollut Control 80: 614-31 (1981) (10) Coleman WE et al; pp. 305-27 in Analysis and identification of organic substances in water. Keith L, ed, Ann Arbor, MI: Ann Arbor Sci (1976) (11) Page RD et al; J AOAC Int 76: 26-31 (1993)]**PEER REVIEWED**

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).
[(1) Ewing BB et al; Monitoring to detect previously unrecognized pollutants in surface waters USEPA 560/6-77-015 (appendix USEPA 560/6-77-015a) (1977) (2) Sheldon LS, Hites RA; Environ Sci Technol 12: 1188-94 (1978) (3) Goodley PC, Gordon M; KY Acad Sci 37: 11-5 (1976) (4) Zuercher F, Giger W; Vom Wasser 47: 37-55 (1976) (5) Zou H et al; Wat Res 30: 2003-2008 (1996) (6) Sauer TC Jr; Org Geochem 3: 91-101 (1981) (7) Sauer TC Jr et al; Mar Chem 7: 1-16 (1978) (8) Gschwend PM et al; Environ Sci Technol 16: 31-8 (1982) (9) Gotz R et al; Chemosphere 36: 2103-18 (1998)]**PEER REVIEWED**

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).
[(1) Kawamura K, Kaplan IR; Environ Sci Technol 17: 497-501 (1983) (2) Ligocki MP et al; Atmos Environ 19: 1609-17 (1985)]**PEER REVIEWED**

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).
[(1) USEPA; Treatability Manual p. I.9.10-1 to I.9.10-5 USEPA 600/2-82-001a (1981) (2) Sexton K, Westberg H; Environ Sci Technol 14: 329-32 (1980) (3) Tsani-Bazaca E et al; Environ Technol Lett 2: 303-16 (1981)]**PEER REVIEWED**

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).
[(1) Brosseau J, Heitz M; Atmos Environ 28: 285-93 (1994) (2) Allen MR et al; Environ Sci Technol 31: 1054-61 (1997) (3) Ostermark U, Petersson G: Chemosphere 27: 1719-28 (1993) (4) Gabele P; J air Waste Manage Assoc 47: 945-52 (1997) (5) Baily JC et al; Atmos Environ 24A: 43-52 (1990) (6) Jay K, Stiegltz L; Chemosphere 30: 1249-60 (1995)]**PEER REVIEWED**

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).
[(1) Goodley PC, Gordon M; KY Acad Sci 37: 11-5 (1976) (2) Steinheimer TR et al; Anal Chim Acta 129: 57-67 (1981) (3) Staples CA et al; Environ Toxicol Chem 4: 131-42 (1985) (4) Ferrario JB et al; Bull Environ Contam Toxicol 34: 246-55 (1985) (5) Kawata K et al; Bull Environ Contam Toxicol 58: 893-900 (1997) (6) Iannuzzi TJ et al; Chemosphere 34: 213-31 (1997)]**PEER REVIEWED**

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).
[(1) Brodzinsky R, Singh HB; Volatile Organics in the Atmosphere: An Assessment of Available Data. p 126-7 SRI contract 68-02-3459 (1982) (2) Singh HB et al; Atmospheric measurements of Selected Hazardous Organic Chemicals USEPA 600/53-81-032 (1981) (3) Altshuller AP et al; Environ Sci Technol 5: 1009-16 (1971) (4) Singh HB et al; Atmos Environ 15: 601-12 (1981) (5) Arnts RR, Meeks SA; Biogenic hydrocarbon contribution to the ambient air of selected areas 128 USEPA 600/3-80-023 (1980) (6) Bozzelli JW et al; Analysis of selected toxic and carcinogenic substances in ambient air in New Jersey, NJ Dept Environ Protect (1980) (7) Lonneman WA et al; Hydrocarbons in Houston air. USEPA 600/3-79-018 pp. 44 (1979) (8) Lioy PJ et al; J Water Pollut Control Fed 33: 649-57 (1983) (9) Pilar S, Graydon WF; Environ Sci Technol 7: 628-71 (1973) (10) Termonia M; Comm Eur Comm EUR 7624 pp. 356-61 (1982) (11) Sexton K, Westberg H; Environ Sci Technol 14: 329-32 (1980) (12) Tsani-Bazaca E et al; Chemosphere 11: 11-23 (1982) (13) Derwent RG; pp. 1-15 in Volatile Organic Compounds in the Atmosphere. Hester RE, Harrison RM, Iss Environ Sci Technol No 4, the Royal Society of Chemistry, Cambridge, UK (1995) (14) Chan CC et al; Atmos Environ 28: 2351-59 (1994) (15) Coursimault A et al; Sci Total Environ 169: 17-23 (1995) (16) Dor F et al; J Air Waste Manage Assoc 45: 103-110 (1995)]**PEER REVIEWED**

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).
[(1) Shields HC et al; Indoor air 6: 2-17 (1996) (2) Schaeffer VH et al; J Air Waste Manage Assoc 46: 813-20 (1996) (3) Hollund BE, Moen BE; Ann Occup Hyg 42: 277-81 (1998)]**PEER REVIEWED**

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)
[(1) Brodzinsky R, Singh HB; Volatile Organics in the Atmosphere: An Assessment of Available Data. pp. 126-7 SRI contract 68-02-3459 (1982) (2) Helmig D et al; Chemosphere 19: 1399-1412 (1989) (3) Derwent RG; pp. 1-15 in Volatile Organic Compounds in the Atmosphere, Hester RE, Harrison RM. Iss Environ Sci Technol No 4, the Royal Society of Chemistry, Cambridge, UK (1995)]**PEER REVIEWED**

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).
[(1) Brodzinsky R, Singh HB; Volatile Organics in the Atmosphere: An Assessment of Available Data. pp. 126-7 SRI contract 68-02-3459 (1982) (2) Bozzelli JW et al; Analysis of selected toxic and carcinogenic substances in ambient air in New Jersey, NJ Dept Environ Protect (1980) (3) Tsani-Bazaca E et al; Chemosphere 11: 11-23 (1982) (4) American Petroleum Inst; Gasoline Vapor Exposure Assessment at Service Stations. American Petroleum Inst Washington, DC: API Publ 4553 (1993) (5) Zielinska B et al; Atmos Environ 12: 2269-86 (1996)]**PEER REVIEWED**

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).
[(1) Coleman EC et al; J Agric Food Chem 29: 42-8 (1981) (2) Dumont JP, Adda J; J Agric Food Chem 26: 364-7 (1978) (3) Ho CT et al; J Agric Food Chem 31: 336-42 (1983) (4) Tang JT et al; J Agric Food Chem 31: 1287-92 (1983) (5) Chung TY et al; J Agric Food Chem 41: 1467-70 (1993) (6) King MF et al; J Agric Food Chem 41: 1974-81 (1993)]**PEER REVIEWED**

Plant Concentrations:

Toluene was identified, not quantified, in the Korean Chamachwi plant(1).
[(1) Chung TY et al; J Agric Food Chem 41: 1693-97 (1993)]**PEER REVIEWED**

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).
[(1) USEPA; Ambient Water Quality Criteria for Toluene. pp. C-1 to C-7 (1980) (2) Ferrario JB et al; Bull Environ Contam Toxicol 34: 246-55 (1985) (3) Misharina TA, Golovnya RV; J High Resol Chromat 15: 332-34 (1992)]**PEER REVIEWED**

Milk Concentrations:

Toluene was identified, not quantified, in 8 samples of mothers' milk from 4 urban areas(1).
[(1) Pellizzari ED et al; Bull Environ Contam Toxicol 28: 322-8 (1982)]**PEER REVIEWED**

Other Environmental Concentrations:

Light oil from coal 12-20% toluene; crude oil 1.2-2.4% auto fuel 8-12%(1).
[(1) Walker P; Air Pollution Assessment of Toluene. p. 1-22, 46-92 MTR-7215 Mitre Corp, McLean VA (1976)]**PEER REVIEWED**

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.
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1723]**PEER REVIEWED**

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.
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1723]**PEER REVIEWED**

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.
[40 CFR 180.1001(d) (7/1/99)]**PEER REVIEWED**

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.
[40 CFR 716.120 (7/1/99)]**PEER REVIEWED**

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).
[40 CFR 302.4 (7/1/99)]**PEER REVIEWED**

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).
[40 CFR 261.33 (7/1/99)]**PEER REVIEWED**

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.
[40 CFR 261.31 (7/1/99)]**PEER REVIEWED**

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.
[40 CFR 60.489 (7/1/99)]**PEER REVIEWED**

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 Air Act as amended in 1990, Sect. 112 (b) (1) Public Law 101-549 Nov. 15, 1990]**PEER REVIEWED**

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.
[40 CFR 401.15 (7/1/99)]**PEER REVIEWED**

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.
[40 CFR 116.4 (7/1/99)]**PEER REVIEWED**

For the protection of human health from the toxic properties of toluene ... the ambient water criterion is determined to be 14.3 mg/l.
[USEPA; Quality Criteria for Water 1986: Toluene (1986) EPA 440/5-86-001]**PEER REVIEWED**

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.
[40 CFR 141.61 (7/1/99)]**PEER REVIEWED**

Federal Drinking Water Standards:

EPA 1000 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

Federal Drinking Water Guidelines:

EPA 1000 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

State Drinking Water Standards:

(CA) CALIFORNIA 150 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

State Drinking Water Guidelines:

(AZ) ARIZONA 2000 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

(FL) FLORIDA 40 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

(ME) MAINE 1400 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

(MN) MINNESOTA 1000 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

(WA) WASHINGTON 800 ug/l
[USEPA/Office of Water; Federal-State Toxicology and Risk Analysis Committee (FSTRAC). Summary of State and Federal Drinking Water Standards and Guidelines (11/93), p. ]**PEER REVIEWED**

FDA Requirements:

Toluene is an indirect food additive for use only as a component of adhesives.
[21 CFR 175.105 (4/1/99)]**PEER REVIEWED**

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.
[40 CFR 180.1001(d) (7/1/99)]**PEER REVIEWED**

Chemical/Physical Properties:

Molecular Formula:

C7-H8
**PEER REVIEWED**

Molecular Weight:

92.14
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 3-55]**PEER REVIEWED**

Color/Form:

Colorless liquid.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Odor:

Sweet, pungent, benzene-like odor.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Boiling Point:

110.6 deg C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 3-55]**PEER REVIEWED**

Melting Point:

-94.9 deg C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 3-55]**PEER REVIEWED**

Corrosivity:

Noncorrosive liquid.
[USEPA; Ambient Water Quality Doc: Toluene p.A-1 (1980) EPA 440/5-80-075)]**PEER REVIEWED**

Critical Temperature & Pressure:

Critical temperature: 591.75 K; Critical pressure: 4.108 MPa
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 6-54]**PEER REVIEWED**

Density/Specific Gravity:

0.8636 @ 20 deg C/4 deg C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 3-55]**PEER REVIEWED**

Heat of Combustion:

3910.3 KJ/mol
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 6-111]**PEER REVIEWED**

Heat of Vaporization:

38.01 KJ/mol @ 25 deg C
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 6-111]**PEER REVIEWED**

Octanol/Water Partition Coefficient:

log Kow= 2.73
[Hansch, C., Leo, A., D. Hoekman. Exploring QSAR - Hydrophobic, Electronic, and Steric Constants. Washington, DC: American Chemical Society., 1995., p. 31]**PEER REVIEWED**

Solubilities:

Miscible with alcohol, chloroform, ether, acetone, glacial acetic acid, carbon disulfide
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1626]**PEER REVIEWED**

Soluble in ethanol, benzene, diethyl ether, acetone, chloroform, glacial acetic acid and carbon disulfide; insoluble in water.
[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 79 (1989)]**PEER REVIEWED**

In water, 526 mg/l @ 25 deg C
[Sanemasa I et al; Bull Chem Soc Japan 55: 1054-62 (1982)]**PEER REVIEWED**

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)
[Weast, R.C. (ed.). Handbook of Chemistry and Physics. 60th ed. Boca Raton, Florida: CRC Press Inc., 1979., p. C-518]**PEER REVIEWED**

Index of refraction: 1.4967 @ 20 deg C/D
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 3-55]**PEER REVIEWED**

IR: 3574 (Coblentz Society Spectral Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 360]**PEER REVIEWED**

UV: 155 (Sadtler Research Laboratories Spectral Collection)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 360]**PEER REVIEWED**

NMR: 157 (Varian Associates NMR Spectra Catalogue)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 360]**PEER REVIEWED**

MASS: 189 (Atlas of Mass Spectral Data, John Wiley & Sons, New York)
[Weast, R.C. and M.J. Astle. CRC Handbook of Data on Organic Compounds. Volumes I and II. Boca Raton, FL: CRC Press Inc. 1985., p. V2 360]**PEER REVIEWED**

Intense mass spectral peaks: 65 m/z, 91 m/z, 92 m/z
[Pfleger, K., H. Maurer and A. Weber. Mass Spectral and GC Data of Drugs, Poisons and their Metabolites. Parts I and II. Mass Spectra Indexes. Weinheim, Federal Republic of Germany. 1985., p. 104]**PEER REVIEWED**

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
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 6-137]**PEER REVIEWED**

Vapor Density:

3.1 (Air=1)
[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. 1304-5]**PEER REVIEWED**

Vapor Pressure:

28.4 mm Hg @ 25 deg C
[Daubert, T.E., R.P. Danner. Physical and Thermodynamic Properties of Pure Chemicals Data Compilation. Washington, D.C.: Taylor and Francis, 1989., p. ]**PEER REVIEWED**

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
[Lide, D.R. (ed.). CRC Handbook of Chemistry and Physics. 79th ed. Boca Raton, FL: CRC Press Inc., 1998-1999., p. 6-173]**PEER REVIEWED**

Other Chemical/Physical Properties:

CONVERSION FACTORS: 1 PPM= 3.76/CU M; 1 MG/L= 226 PPM.
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 66]**PEER REVIEWED**

Ratio of Specific Heats of Vapor (Gas): 1.089; floats on water
[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**

Partition coefficients at 37 deg C for toluene into blood= 15.6; into oil= 1,470.
[Sato A, Nakajima T; Scand J Work Environ Health 13: 81-93 (1987)]**PEER REVIEWED**

Henry's Law constant = 6.64X10-3 atm-cu m/mole @ 25 deg C
[Mackay D et al; Environ Sci Technol 13: 333-6 (1979)]**PEER REVIEWED**

Hydroxyl radical rate constant = 5.96X10-12 cu cm/molecule-sec @ 25 deg C
[Atkinson R; J Phys Chem Ref Data Monograph No. 2 (1994)]**PEER REVIEWED**

Chemical Safety & Handling:

DOT Emergency Guidelines:

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ 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. Runoff to sewer may create fire or explosion hazard. Containers may explode when heated. Many liquids are lighter than water.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ 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.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ Public Safety: CALL Emergency Response Telephone Number ... . As an immediate precautionary measure, isolate spill or leak area for at least 50 meters (150 feet) in all directions. Keep unauthorized personnel away. Stay upwind. Keep out of low areas. Ventilate closed spaces before entering.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ Protective Clothing: Wear positive pressure self-contained breathing apparatus (SCBA). Structural firefighters' protective clothing will only provide limited protection.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ 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.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ 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 tanks engulfed in fire. For massive fire, use unmanned hose holders or monitor nozzles; if this is impossible, withdraw from area and let fire burn.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ 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.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

/GUIDE 130: FLAMMABLE LIQUIDS (NON-POLAR/WATER-IMMISCIBLE/NOXIOUS)/ First Aid: Move victim to fresh air. Call 911 or emergency medical service. Give 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. In case of burns, immediately cool affected skin for as long as possible with cold water. Do not remove clothing if adhering to skin. 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.
[U.S. Department of Transportation. 2004 Emergency Response Guidebook. A Guide book for First Responders During the Initial Phase of a Dangerous Goods/Hazardous Materials Incident. Washington, D.C. 2004G-130]**QC REVIEWED**

Odor Threshold:

2.14 ppm (8 mg/cu m). Odor recognition level is reported as 1.03 to 140 ug/cu m.
[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**

Odor in air= 1.30x10+11 mol/cu cm
[Fazzalari, F.A. (ed.). Compilation of Odor and Taste Threshold Values Data. ASTM Data Series DS 48A (Committee E-18). Philadelphia, PA: American Society for Testing and Materials, 1978., p. 158]**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**

Fire Potential:

Flammable liquid. A very dangerous fire hazard when exposed to heat, flame, or oxidizers.
[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**

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.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-87]**PEER REVIEWED**

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.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-87]**PEER REVIEWED**

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.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-87]**PEER REVIEWED**

Flammable Limits:

Lower flammable limit: 1.1% by volume; Upper flammable limit: 7.1% by volume
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-87]**PEER REVIEWED**

Flash Point:

40 deg F (4 deg C) (Closed cup)
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-87]**PEER REVIEWED**

16 deg C (Open cup)
[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**

Autoignition Temperature:

896 DEG F (480 DEG C)
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 325-87]**PEER REVIEWED**

Fire Fighting Procedures:

TO FIGHT FIRE, USE FOAM, CO2, DRY CHEMICAL.
[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**

Approach fire from upwind to avoid hazardous vapors and toxic decomposition
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-127]**PEER REVIEWED**

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.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

Toxic Combustion Products:

MODERATELY DANGEROUS; WHEN HEATED, EMITS TOXIC FUMES /WHICH/ CAN REACT VIGOROUSLY WITH OXIDIZING MATERIALS.
[Sax, N.I. Dangerous Properties of Industrial Materials. 6th ed. New York, NY: Van Nostrand Reinhold, 1984., p. 2588]**PEER REVIEWED**

Firefighting Hazards:

Vapor is heavier than air and may travel a considerable distance to a source of ignition and flash back.
[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**

Flame speed equals 37 cm/sec.
[Environment Canada; Tech Info for Problem Spills: Toluene (Draft) p.3 (1979)]**PEER REVIEWED**

Explosive Limits & Potential:

LEL: 1.27%; UEL: 7%.
[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**

Hazardous Reactivities & Incompatibilities:

Frozen bromine trifluoride reacts violently with toluene at -80 deg C.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 91]**PEER REVIEWED**

A mixture of /dinitrogen/ tetraoxide and toluene exploded, possibly initiated by impurities.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1353]**PEER REVIEWED**

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.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1165]**PEER REVIEWED**

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 ... .
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 189]**PEER REVIEWED**

Interaction /of uranium hexafluoride/ with ... toluene ... is very vigorous, with separation of carbon, and violent with ethanol or water.
[Bretherick, L. Handbook of Reactive Chemical Hazards. 4th ed. Boston, MA: Butterworth-Heinemann Ltd., 1990, p. 1126]**PEER REVIEWED**

Incompatible with strong oxidizers.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 869]**PEER REVIEWED**

Strong oxidizers.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Reacts photochemically with nitrogen oxides or halogens to form nitrotoluene, nitrobenzene and nitrophenol and halogenated products, respectively.
[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 79 (1989)]**PEER REVIEWED**

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.
[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**

Hazardous Decomposition:

When heated to decomposition it emits acrid smoke and irritating fumes.
[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**

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. ...
[Heare SF et al; 1986 Hazard Matl Spill Conf p.12-18 (1986)]**PEER REVIEWED**

Immediately Dangerous to Life or Health:

500 ppm
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Protective Equipment & Clothing:

Protective clothing should include gloves, barrier creams, eye goggles or face shields, and a cartridge-type or self-contained breathing apparatus.
[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. 1332]**PEER REVIEWED**

WEAR SELF-CONTAINED BREATHING APPARATUS; WEAR GOGGLES IF EYE PROTECTION NOT PROVIDED.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-127]**PEER REVIEWED**

Eye protection: Glasses having shatter-resistant glass or equivalent lenses and side shields to protect the eyes from toluene splashes.
[NIOSH; Criteria Document: Toluene p.8 (1973) DHEW Pub. NIOSH 73-11023]**PEER REVIEWED**

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

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.
[Sittig, M. Handbook of Toxic and Hazardous Chemicals and Carcinogens, 1985. 2nd ed. Park Ridge, NJ: Noyes Data Corporation, 1985., p. 870]**PEER REVIEWED**

Wear appropriate personal protective clothing to prevent skin contact.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Wear appropriate eye protection to prevent eye contact.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

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.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

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.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

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.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Preventive Measures:

Drench-type showers, eye-wash fountains should be installed and maintained to provide prompt, immediate access.
[NIOSH; Criteria Document: Toluene p.9 (1973) DHEW Pub. NIOSH 73-11023]**PEER REVIEWED**

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

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.
[Hart C; J Environ Health 49 (5): 282-86 (1987)]**PEER REVIEWED**

Contact lenses should not be worn when working with this chemical.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

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.
**PEER REVIEWED**

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.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

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.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

If material leaking (not on fire): Consider evacuation from downwind area based on amount of material spilled, location and weather conditions.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

The worker should immediately wash the skin when it becomes contaminated.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Work clothing that becomes wet should be immediately removed due to its flammability hazard.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

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)./
[49 CFR 171.2; U.S. National Archives and Records Administration's Electronic Code of Federal Regulations. Available from: http://www.gpoaccess.gov/ecfr/ as of February 15, 2006 ]**QC REVIEWED**

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.
[International Air Transport Association. Dangerous Goods Regulations. 47th Edition. Montreal, Quebec Canada. 2006., p. 263]**PEER REVIEWED**

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.
[International Maritime Organization. International Maritime Dangerous Goods Code. London, UK. 2004., p. 55]**PEER REVIEWED**

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.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-127]**PEER REVIEWED**

Use ambient storage temperature.
[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**

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.
[Fire Protection Guide to Hazardous Materials. 12 ed. Quincy, MA: National Fire Protection Association, 1997., p. 49-197]**PEER REVIEWED**

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.
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 4]**PEER REVIEWED**

Fluorocarbon water foam may be used to diminish vapors and provide wet down.
[Environment Canada; Tech Info for Problem Spills: Toluene (Draft) p.94 (1982)]**PEER REVIEWED**

Cellosive and hycar absorbent materials, may be used for vapor suppression and/or containment of toluene.
[Environment Canada; Tech Info for Problem Spills: Toluene (Draft) p.94 (1982)]**PEER REVIEWED**

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.
[Environment Canada; Tech Info for Problem Spills: Toluene (Draft) p.94 (1982)]**PEER REVIEWED**

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.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

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.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

Environmental considerations - Air Spill: Apply water spray or mist to knock down vapors.
[Association of American Railroads. Emergency Handling of Hazardous Materials in Surface Transportation. Washington, DC: Association of American Railroads, Bureau of Explosives, 1994., p. 1057]**PEER REVIEWED**

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.
[40 CFR 240-280, 300-306, 702-799 (7/1/90)]**PEER REVIEWED**

Toluene is a waste chemical stream constituent which may be subjected to ultimate disposal by controlled incineration.
[USEPA; Engineering Handbook for Hazardous Waste Incineration p.2-9 (1981) EPA 68-03-3025]**PEER REVIEWED**

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.
[USEPA; Engineering Handbook for Hazardous Waste Incineration p.3-16 (1981) EPA 68-03-3025]**PEER REVIEWED**

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.
[Environment Canada; Tech Info for Problem Spills: Toluene (Draft) p.96 (1982)]**PEER REVIEWED**

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.
[Mackison, F. W., R. S. Stricoff, and L. J. Partridge, Jr. (eds.). NIOSH/OSHA - Occupational Health Guidelines for Chemical Hazards. DHHS(NIOSH) Publication No. 81-123 (3 VOLS). Washington, DC: U.S. Government Printing Office, Jan. 1981., p. 4]**PEER REVIEWED**

The following wastewater treatment technologies have been investigated for toluene: biological treatment.
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-48 (1982)]**PEER REVIEWED**

The following wastewater treatment technologies have been investigated for toluene: stripping.
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-97 (1982)]**PEER REVIEWED**

The following wastewater treatment technologies have been investigated for toluene: solvent extraction.
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-112 (1982)]**PEER REVIEWED**

The following wastewater treatment technologies have been investigated for toluene: activated carbon.
[USEPA; Management of Hazardous Waste Leachate, EPA Contract No.68-03-2766 p.E-148 (1982)]**PEER REVIEWED**

Occupational Exposure Standards:

OSHA Standards:

Permissible Exposure Limit: Table Z-2 8-hr Time Weighted Avg: 200 ppm.
[29 CFR 1910.1000 (7/1/99)]**PEER REVIEWED**

Permissible Exposure Limit: Table Z-2 Acceptable Ceiling Concentration: 300 ppm.
[29 CFR 1910.1000 (7/1/99)]**PEER REVIEWED**

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.
[29 CFR 1910.1000 (7/1/99)]**PEER REVIEWED**

Vacated 1989 OSHA PEL TWA 100 ppm (375 mg/cu m); STEL 150 ppm (560 mg/cu m) is still enforced in some states.
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 372]**PEER REVIEWED**

Threshold Limit Values:

8 Hr Time Weighted Avg (TWA): 50 ppm, skin
[ 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**

Excursion Limit Recommendation: Excursions in worker exposure levels may exceed 3 times the TLV-TWA for no more than a total of 30 minutes during a work day, and under no circumstances should they exceed 5 times the TLV-TWA, provided that the TLV-TWA is not exceeded.
[ 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. 5]**PEER REVIEWED**

Biological Exposure Index (BEI): Determinant: o-Cresol in urine; Sampling Time: end of shift; BEI: 0.5 mg/L. The determinant may be present in biological specimens collected from subjects who have not been occupationally exposed, at a concentration which could affect interpretation of the result. Such background concentrations are incorporated in the BEI value.
[ 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. 96]**PEER REVIEWED**

Biological Exposure Index (BEI): Determinant: Hippuric acid in urine; Sampling Time: end of shift; BEI: 1.6 g/g creatinine. The determinant may be present in biological specimens collected from subjects who have not been occupationally exposed, at a concentration which could affect interpretation of the result. Such background concentrations are incorporated in the BEI value. The determinant is nonspecific, since it is also observed after exposure to other chemicals.
[ 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. 96]**PEER REVIEWED**

Biological Exposure Index (BEI): Determinant: toluene in blood; Sampling Time: prior to last shift of workweek; BEI: 0.05 mg/L.
[ 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. 96]**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**

NIOSH Recommendations:

Recommended Exposure Limit: 10 Hr Time-Weighted Avg: 100 ppm (375 mg/cu m).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Recommended Exposure Limit: 15 Min Short-Term Exposure Limit: 150 ppm (560 mg/cu m).
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

Immediately Dangerous to Life or Health:

500 ppm
[NIOSH. NIOSH Pocket Guide to Chemical Hazards. DHHS (NIOSH) Publication No. 97-140. Washington, D.C. U.S. Government Printing Office, 1997., p. 310]**PEER REVIEWED**

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).
[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. 1577]**PEER REVIEWED**

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.
[American Industrial Hygiene Association. The AIHA 1999 Emergency Response Planning Guidelines and Workplace Environmental Exposure Level Guides Handbook. American Industrial Hygiene Association. Fairfax, VA 1999., p. 27]**PEER REVIEWED**

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.
[Budavari, S. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 1996., p. 1626]**PEER REVIEWED**

DILUENT FOR PHOTOGRAVURE INKS
[International Labour Office. Encyclopedia of Occupational Health and Safety. Vols. I&II. Geneva, Switzerland: International Labour Office, 1983., p. 2184]**PEER REVIEWED**

IN FABRIC & PAPER COATING, MFR ARTIFICIAL LEATHER
[Browning, E. Toxicity and Metabolism of Industrial Solvents. New York: American Elsevier, 1965., p. 67]**PEER REVIEWED**

Used in cements, solvents, spot removers, cosmetics, antifreezes, and inks.
[Gleason MN; Chem Tox of Comm Prod, 3rd Ed, 1969 as cited in USEPA; Health Assessment Document: Toluene (Draft) (1982) EPA-600/8-82-008]**PEER REVIEWED**

Asphalt and naphtha constituent. Detergent manufacture.
[USEPA. Identification of Organic Cmpds in Effluents from Industrial Sources, (1975) EPA 560/3-75-002]**PEER REVIEWED**

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.
[Verschueren, K. Handbook of Environmental Data on Organic Chemicals. 3rd ed. New York, NY: Van Nostrand Reinhold Co., 1996., p. 1722]**PEER REVIEWED**

Fuel blending
[ITII. Toxic and Hazardous Industrial Chemicals Safety Manual. Tokyo, Japan: The International Technical Information Institute, 1988., p. 525]**PEER REVIEWED**

DENATURANT
**PEER REVIEWED**

The largest chemical use for toluene is the production of benzene and urethane via hydrodealkylation.
[CHEMICAL PRODUCTS SYNOPSIS: Toluene, 1985]**PEER REVIEWED**

Used in production of drugs of abuse.
[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**

Manufacturers:

Amoco Corp., 200 East Randolph Drive, Chicago, IL 60601, (312)856-6111; Production site: Texas City, TX 77590
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

BP America, 200 Public Square, Cleveland OH 44114-2375. (216) 586-4141; Production sites: Alliance, LA 70037; Lima, OH 45804
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

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
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Coastal Refining and Marketing, 9 Greenway Plaza, Houston, TX 77046, (713)877-6559; Production site: Corpus Christi, TX 78403
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Coastal Eagle Point Co., 9 PO Box 1000, US Route 130& I295 Westville, NJ 08093, (609)853-3100; Production site: Westville, NJ 08093
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Chevron Chemical Corp., 6001 Bollinger Canyon Rd., San Ramon, CA 94583, (925)842-5500; Production site: Port Arthur, TX 77460
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Dow Chemical USA, 2020 Dow Center, Midland, MI 48674, (517) 636-1000; Production site: Plaquemine, LA 70765
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

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
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Exxon Chemical Co., 13501 Katy Freeway, Houston, TX 77079, (281)871-6000; Production site: Baton Rouge, LA 70821
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Fina Oil and Chemical Co., PO Box 2159, Dallas, TX 75221-2159, (214) 750-2400; Production site: Port Arthur, TX 77460
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

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
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Koch Refining Co., PO Box 2256, Wichita, KS 67201, (316)828-5500; Production site: Corpus Christi, TX 78403
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Lyondell-CITGO Refining Co., 1200 Lawndale, Houston, TX 77017, (713)321-4111; Production site: Houston, TX 77252
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

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
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Mobil Chemical Co., 3225 Gallows Rd., Fairfax, VA 22037-0001, (703)846-3000; Production sites: Chalmette, LA 70043; Beaumont, TX 77704-3868
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Phillips Petroleum Co., Phillips Building, Bartlesville, OK 74004, (918)661-6600; Production site: Sweeney, TX 77480
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Phillips Puerto Rico Core Inc., Road 3 Route 710, Barrio Las Mareas Guayama PR 00785, (787)864-1515; Production site: Guayama, PR 00785
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Shell Chemical Co., One Shell Plaza, PO Box 2463, Houston, TX 77252-2463, (713)241-6161; Production site: Deer Park, TX 77536
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Sun Company Inc., 1801 Market St., Philadelphia, PA 19103, (800) 825-3535; Production sites: Marcus Hook, PA 19061; Toledo, OH 43693; Tulsa, OK 74102
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Texaco Refining and Marketing Inc., 10 Universal City Plaza, Universal City, CA 91608-1097, (818)505-2000; Production site: El Dorada, KS 67042
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Ultramar Diamond Corp., 6000 N. Loop 1604, W. San Antonio, TX 78249-1112, (210)592-2000; Production site: Three Rivers, TX 78071
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Valero Energy Corp., San Antonio Valero Tower, W 1H 10, San Antonio, TX 78229-4718, (210)370-2000; Production site: Houston, TX 77012-2408
[SRI. 1998 Directory of Chemical Producers -United States of America. SRI International, Menlo Park, CA. 1998., p. 955]**PEER REVIEWED**

Methods of Manufacturing:

UNRECOVERED COMPONENT OF GASOLINE
**PEER REVIEWED**

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.
[DCE/NCI; Monograph On Human Exposure To Chemicals In The Workplace: Toluene p.2-1 (1985)]**PEER REVIEWED**

(1) By catalytic reforming of petroleum. (2) By fractional distillation of coal tar light oil.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 1113]**PEER REVIEWED**

General Manufacturing Information:

28th Highest-volume chemical produced in the USA (1995).
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 1113]**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.
[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**

Grades: Research 99.99%; Pure 99.98% Toluene
[Flick, E.W. Industrial Solvents Handbook. 3rd ed. Park Ridge, NJ: Noyes Publications, 1985., p. 48]**PEER REVIEWED**

Grades: 1st degree nitration; 2nd degree commercial; 90% solvent
[DCE/NCI; Monograph On Human Exposure To Chemicals In The Workplace: Toluene p.1-1 (1985)]**PEER REVIEWED**

Grade: (Usually defined in terms of boiling ranges) Pure, commercial, straw-colored, nitration, scintilation, industrial.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 1113]**PEER REVIEWED**

Impurities:

... Commercial grades /of toluene/ usually contain small amounts of benzene as an impurity.
[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**

Technical grades (90-120 deg C boiling range) are less pure and may contain up to 25% benzene as well as other hydrocarbons.
[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 80 (1989)]**PEER REVIEWED**

Commercial grades /of toluene/ can ... contain polynuclear aromatic hydrocarbons (PAH), including pyrene, fluoranthrene, and benzo[ghi]perylene.
[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. 1568]**PEER REVIEWED**

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)
**PEER REVIEWED**

Benzene, 46%; gasoline blending, 37%; solvent, 8%; toluene diisocyanate, 7%; miscellaneous chemicals, 2% (1985) /estimate/
[CHEMICAL PRODUCTS SYNOPSIS: Toluene, 1985]**PEER REVIEWED**

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.
[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 82 (1989)]**PEER REVIEWED**

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.
[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 82 (1989)]**PEER REVIEWED**

U. S. Production:

(1981) 4.68X10+12 G (ALL USES, 93% CHEM GRADE)
[US INTERNATIONAL TRADE COMMISSION, WASH, DC 20436; SOC SERIES C/P-82-1]**PEER REVIEWED**

(1977) 1.50X10+12 G
**PEER REVIEWED**

(1982) 1.54X10+12 G
**PEER REVIEWED**

(1985) 2.30X10+12 g
[USITC. SYN ORG CHEM-U.S. PROD/SALES 1985 p.19]**PEER REVIEWED**

(1990) 6.21 billion lb
[Chem & Engineering News 70 (15): 17 (4/13/92)]**PEER REVIEWED**

(1991) 6.30 billion lb
[Chem & Engineering News 71 (15): 11 (4/12/93)]**PEER REVIEWED**

(1992) 5.81 billion lb
[Chem & Engineering News 72 (15): 13 (4/11/94)]**PEER REVIEWED**

(1993) 6.38 billion lb
[Chem & Engineering News 72 (15): 13 (4/11/94)]**PEER REVIEWED**

(1993) 2.276572X10+9 kg
[United States International Trade Commission. Synthetic Organic Chemicals - United States Production and Sales, 1993. USITC Publication 2810, Nov. 1994. Washington, D.C., p. 3-13]**PEER REVIEWED**

U. S. Imports:

(1978) 1.92X10+11 G
**PEER REVIEWED**

(1983) 2.73X10+11 G
**PEER REVIEWED**

(1985) 1.57X10+8 gal
[BUREAU OF THE CENSUS. U.S. IMPORTS FOR CONSUMPTION AND GENERAL IMPORTS 1985 p.1-547]**PEER REVIEWED**

U. S. Exports:

(1978) 3.65X10+11 G
**PEER REVIEWED**

(1983) 1.15X10+11 G
**PEER REVIEWED**

(1985) 2.82X10+7 gal
[BUREAU OF THE CENSUS. U.S. EXPORTS, SCHEDULE E, 1985 p.2-70]**PEER REVIEWED**

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.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 8002-1]**PEER REVIEWED**

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 ...
[Cocheo V et al; Am Ind Hyg Assoc 43 (12): 938-41 (1982)]**PEER REVIEWED**

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.
[Ogata M, Taguchi T; Int Arch Occup Environ Health 59 (3): 263-72 (1987)]**PEER REVIEWED**

Analytic Laboratory Methods:

Quantitative determination of 4 to 40 ppm toluene in water with precision of 10% using IR spectroscopy.
[Amer Water Works Assoc; Standard Methods for the Examination of Water and Waste Water 14th Ed (1976)]**PEER REVIEWED**

Quantitative method for detection of toluene in water by gas chromatography. Levels over 1 ppm can be detected.
[Amer Water Works Assoc; Standard Methods for the Examination of Water and Waste Water 14th Ed (1976)]**PEER REVIEWED**

TOLUENE WAS IDENTIFIED IN WASTE-CONTAMINATED SOIL AND CHEMICAL STILL BOTTOM EXTRACTS BY GC/FOURIER TRANSFORM INFRARED SPECTROMETRY.
[GURKA DF, BETOWSKI LD; ANAL CHEM 54: 1819 (1982)]**PEER REVIEWED**

TWENTY AQ INDUST EFFLUENTS CONTAINING POLLUTANTS WERE ANALYZED USING ISOTOPE DILN & GC/MASS SPECTROMETRY. TOLUENE WAS ONE OF THE POLLUTANTS.
[COLBY BN ET AL; INTERNATIONAL ENVIRONMENT & SAFETY FEB: 8 (1982)]**PEER REVIEWED**

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%.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 1500-1]**PEER REVIEWED**

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.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 4000-1]**PEER REVIEWED**

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).
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 1501-1]**PEER REVIEWED**

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%.
[USEPA; Methods for the Determination of Organic Compounds in Finished Drinking Water and Raw Source Water (1986)]**PEER REVIEWED**

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.
[USEPA; Methods for the Determinatioon of Organic Compounds in Finished Drinking Water and Raw Source Water (1986)]**PEER REVIEWED**

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.
[40 CFR 136 97/1/91)]**PEER REVIEWED**

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.
[40 CFR 136 (7/1/91)]**PEER REVIEWED**

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%.
[40 CFR 136 (7/1/91)]**PEER REVIEWED**

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.
[USEPA; Test Methods for Evaluating Solid Waste SW-846 (1986)]**PEER REVIEWED**

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.
[USEPA; Test Methods for Evaluating Solid Waste SW-846 (1986)]**PEER REVIEWED**

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.
[USEPA; Methods for the Determination of Organic Compounds in Finished Drinking Water and Raw Source Water (1986)]**PEER REVIEWED**

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.
[USEPA; Methods for the Determination of Organic Compounds in Finished Drinking Water and Raw Source Water (1986)]**PEER REVIEWED**

AOB Method OA-002-1. Volatile Organic Compounds by GC/MS Analysis of Tenax/CMS Cartridge and Summa Canister Samples. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VA-003-1. Volatile Organic Compounds (VOCs) in Air by Portable GC/PID. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VA-005-1. Volatile Organic Compounds (VOCs) in Ambient Air by Purge and Trap Gas Chromatography. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VA-006-1. Volatile Organic Compounds (VOCs) in Ambient Air by Direct Portable GC/PID. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VA-007-1. Volatile Organic Compounds (VOCs) in Ambient Air by GC/PID, GC/PID/FID, or GC/FID. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VG-001-1. Volatile Organics in Soil Gas - Adsorbent Tube Method. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VG-006-1. Volatile Organic Compounds (VOCs) in Ambient Air by Purge and Trap GC. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AOB Method VG-010-1. Volatile Organic Compounds (VOCs) in Soil Gas by Direct Portable GC. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AREAL Method IP-1A . Determination of Volatile Organic Compounds (VOCs) in Indoor Air Using Stainless Steel Canisters. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

AREAL Method IP-1B . Determination of Volatile Organic Compounds (VOCs) in Indoor Air using Solid Absorbent Tubes. No detection limit.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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.
[USEPA; EMMI. EPA's Environmental Monitoring Methods Index. Version 1.1. PC# 4082. Rockville, MD: Government Institutes (1997)]**PEER REVIEWED**

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/
[Lautenberger WJ et al; Am Ind Hyg Assoc J 41 (10): 737-47 (1980)]**PEER REVIEWED**

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.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 1500-1]**PEER REVIEWED**

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.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 4000-1]**PEER REVIEWED**

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.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 8002-1]**PEER REVIEWED**

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.
[U.S. Department of Health and Human Services, Public Health Service. Centers for Disease Control, National Institute for Occupational Safety and Health. NIOSH Manual of Analytical Methods, 3rd ed. Volumes 1 and 2 with 1985 supplement, and revisions. Washington, DC: U.S. Government Printing Office, February 1984., p. 1501-1]**PEER REVIEWED**

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.
[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**

Grades: Research 99.99%; Pure 99.98%
[Flick, E.W. Industrial Solvents Handbook. 3rd ed. Park Ridge, NJ: Noyes Publications, 1985., p. 48]**PEER REVIEWED**

Grades: 1st degree nitration; 2nd degree commercial; 90% solvent
[DCE/NCI; Monograph On Human Exposure To Chemicals In The Workplace: Toluene p.1-1 (1985)]**PEER REVIEWED**

Grade: (Usually defined in terms of boiling ranges) Pure, commercial, straw-colored, nitration, scintilation, industrial.
[Lewis, R.J., Sr (Ed.). Hawley's Condensed Chemical Dictionary. 13th ed. New York, NY: John Wiley & Sons, Inc. 1997., p. 1113]**PEER REVIEWED**

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.