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IDENTIFICATION AND USE: Toluene is a colorless liquid.Toluene did not induce sister chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells in the presence or absence of exogenous metabolic activation.Toluene 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.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.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.ANIMAL STUDIES: Rats were studied to assess the effects of acute binge-like toluene inhalations (15 or 30 min; ~5,000 ppm) on tasks that examine locomotion, exploration, balance, gait, and neurological functioning for adolescent (1 month), young adult (2-3 months), adult (5-6 months), and older adult (10-12 months) rats.HUMAN EXPOSURE AND TOXICITY: 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 lacrymation was seen at 500 mg/cu m. Volunteers exposed to 100 ppm (377 mg/cu m) toluene for 6 hr/day for four days suffered from subjective complaints of headache, dizziness and a sensation of intoxication.Groups of 60 male and female mice that were exposed 6.5 hours/day, 5 days/week for 2 years via inhalation at inhaled 0, 120, 600, or 1200 ppm toluene showed no biologically relevant increases for any non-neoplastic or neoplastic tissue changes.Severe renal tubular acidosis was observed in five pregnant women who were chronic abusers of paints containing toluene.Rats were dosed with 1.3 g/kg toluene subcutaneously during either week 2 (8-15 days) or week 3 (14-20 days) of pregnancy and evaluated for malformations, development of the skeleton, prenatal growth of the brain and liver, postnatal growth, and behavioral effects.The olfactory and respiratory epithelia showed signs of degeneration with nasal inflammation and metaplasia of the olfactory epithelium (principally in the females).Toluene is a component of gasoline, paints, inks, lacquers, paint thinners, adhesives, fingernail polish, cleaning agents, and rubber.BTX (a mixture of benzene, toluene, and xylene) is added to gasoline to improve octane ratings.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).CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene.However, only the duration to recover from deficits in motor functions differed among age groups, with adolescent and young adult rats requiring notably longer recovery times than older rats.Mice exposed 6 hours/day at 100 ppm toluene during days 1 to 17 of pregnancy showed no significant differences in number of implantation sites, number of fetuses, or mean fetal body weight when compared with control.Toluene is a favorite of solvent abusers, who intentionally inhale high concentrations to achieve a euphoric effect.There was maternal mortality in these groups.


Original text

IDENTIFICATION AND USE: Toluene is a colorless liquid. It is not registered for current pesticide use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Toluene is a component of gasoline, paints, inks, lacquers, paint thinners, adhesives, fingernail polish, cleaning agents, and rubber. BTX (a mixture of benzene, toluene, and xylene) is added to gasoline to improve octane ratings. Toluene is used to produce benzene, trinitrotoluene (TNT), nylon, plastics, and polyurethanes. It is also used in production of drugs of abuse. Toluene is a favorite of solvent abusers, who intentionally inhale high concentrations to achieve a euphoric effect. HUMAN EXPOSURE AND TOXICITY: 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 lacrymation was seen at 500 mg/cu m. Volunteers exposed to 100 ppm (377 mg/cu m) toluene for 6 hr/day for four days suffered from subjective complaints of headache, dizziness and a sensation of intoxication. In subjects exposed to 750 mg/cu m for 8 hr, fatigue, muscular weakness, confusion, impaired coordination, enlarged pupils and accommodation disturbances were experienced; at about 3000 mg/cu m, severe fatigue, pronounced nausea, mental confusion, considerable incoordination with staggering gait and strongly affected pupillary light reflexes were observed. After exposure at the high level, muscular fatigue, nervousness and insomnia lasted for several days. Heavy accidental exposure leads to coma. Studies of women exposed to toluene have shown menstrual disturbances, principally associated with abnormal bleeding. n a case study of two adult white males who suffered from toluene intoxication cardiac arrhythmias were noted. Response seemed to be highly variable among individuals. One person exposed for 2 hr to less than 1890 ppm toluene exhibited a rapid heartbeat (sinus tachycardia), while the second person, exposed for 3 hr, exhibited a slow heartbeat (bradycardia). Severe renal tubular acidosis was observed in five pregnant women who were chronic abusers of paints containing toluene. 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. CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes. A study of Finnish individuals monitored in an occupational database during the years 1978 to 1983 showed that there was no increase in cancer risk with individuals exposed to toluene with average blood levels of 0.18 mg/L. Chromosome studies on peripheral blood lymphocytes of 34 rotogravure workers in Italy showed no changes when compared with the control group. 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. ANIMAL STUDIES: Rats were studied to assess the effects of acute binge-like toluene inhalations (15 or 30 min; ~5,000 ppm) on tasks that examine locomotion, exploration, balance, gait, and neurological functioning for adolescent (1 month), young adult (2-3 months), adult (5-6 months), and older adult (10-12 months) rats. Both motor and neurological functions were impaired following acute toluene inhalation at all ages. However, only the duration to recover from deficits in motor functions differed among age groups, with adolescent and young adult rats requiring notably longer recovery times than older rats. When 0.25, 0.5, or 2.0 mL toluene were applied to 0.7% of the total body surface of guinea pigs, none of the animals died, but reduced body-weight gain occurred. Inhalation of 1400 to 2000 ppm toluene by male rats, 8 hours/day for as little as 3 days resulted in reversible, high-frequency hearing loss. Subcutaneous injection of 50 and 500 mg/kg once a day for 10 days caused decreased sperm counts and serum testosterone in male rats. Rats were dosed with 1.3 g/kg toluene subcutaneously during either week 2 (8-15 days) or week 3 (14-20 days) of pregnancy and evaluated for malformations, development of the skeleton, prenatal growth of the brain and liver, postnatal growth, and behavioral effects. The only toluene-induced change was low birth weight and was found in the rats dosed in the third week of pregnancy. Rabbits exposed 24 hours/day at 1000 mg/cu m (265 ppm) from day 6 to 15 of pregnancy showed increased spontaneous abortions. Mice exposed 24 hours/day at 1000 mg/cu m (265 ppm) on days 6 to 15 of pregnancy and rats exposed to 2400 mg/cu m (636 ppm) on days 7 to 15 of pregnancy showed growth and skeletal retardation. Mice exposed 24 hours/day at 133 ppm toluene on days 6 to 13 of pregnancy and rats exposed 24 hours/day at 399 ppm on days 1 to 8 of pregnancy and on days 9 to 14 of pregnancy showed fetal growth retardation and an increase in skeletal anomalies. There was maternal mortality in these groups. Mice exposed 6 hours/day at 100 ppm toluene during days 1 to 17 of pregnancy showed no significant differences in number of implantation sites, number of fetuses, or mean fetal body weight when compared with control. When toluene was applied to shaved interscapular skin of male mice 3 times per week for 4 weeks, followed by a secondary treatment of 3 times per week for up to 112 weeks, no tumors were observed. Groups of 60 male and female mice that were exposed 6.5 hours/day, 5 days/week for 2 years via inhalation at inhaled 0, 120, 600, or 1200 ppm toluene showed no biologically relevant increases for any non-neoplastic or neoplastic tissue changes. When groups of 60 rats of each sex were exposed via inhalation 6.5 hours/day, 5 days/week for 2 years to atmospheres containing 0, 600, or 1200 ppm toluene, nephropathy occurred in nearly all of the rats. The olfactory and respiratory epithelia showed signs of degeneration with nasal inflammation and metaplasia of the olfactory epithelium (principally in the females). No treatment-related neoplasms occurred in the male rats. and the few scattered tumors found in the females were considered not associated with toluene inhalation. 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. ECOTOXICITY STUDIES: The toluene contamination significantly reduced the mass of the cell wall material in the alfalfa roots. Furthermore, the toluene pollution can change the alfalfa root cell wall properties by reducing the cell wall functional groups. These functional groups are probably related to the proteins and polysaccharides in the cell wall.


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