CAS RN: 95-47-6

Toxicity Summary

IDENTIFICATION AND USE: 2-Xylene (o-xylene) is a colorless liquid. It is used in manufacture of phthalic anhydride, vitamin and pharmaceutical syntheses, dyes, insecticides, motor fuels. HUMAN EXPOSURE AND TOXICITY: Severe toxic effects result from exposure to o-xylene at 1,000 ppm or 4,410 mg/cu m for 60 minutes. Symptoms of illness result from exposure to 300 ppm or 1,323 mg/ cu m for 60 minutes. Levels of xylenes in blood reflect recent exposure. The m-and p-xylene isomers usually are measured together and reported as m/p-xylene; the o-xylene isomer is measured and reported separately. ANIMAL STUDIES: In a study on the noradrenaline and dopamine levels in various parts of the forebrain and hypothalamus, rats (six males/group) were exposed to 0 or 2000 ppm o-xylene 6 hr/day for 3 days. The animals were killed within 18 hr after final exposure. There was a significant increase in catecholamine levels and turnover in various parts of the hypothalamus and a decrease in the dopamine turnover in the forebrain of exposed animals. Administration of xylenes to rats caused decreases in liver glutathione (GSH) concentrations, reduction in glutathione concentration was most pronounced after treatment with o-xylene isomer (4.0 mmol/kg). Exposure of rats to 2000 ppm of o-xylene for 3 days increased hepatic cytochrome P450 concentration and reduced nicotinamide adenine dinucleotide cytochrome C reductase activity. In kidney microsomes an increased concentration of cytochrome P450 was obtained following exposure to o-xylene. Exposures at 1450 ppm of o-xylene reduced the respiratory rate of mice 50% in a manner consistent with sensory irritation. Comparison of the individual xylene isomers showed that the irritant effects of m- and o-xylene as quantified by measurements of respiratory rate in mice are more pronounced than those of p-xylene, with o-xylene having the most prolonged effect. Rats, guinea-pigs, monkeys, and dogs were exposed either to 780 ppm (3368 mg/cu m) o-xylene for 8 hours per day on five days per week for six weeks or to 78 ppm (337 mg/cu m) continuously for 90 days. No significant change in body weight or in hematological parameters and no significant toxicity were observed after histopathological examination of all major organs. Male rats inhaling air containing o-xylene, 4750 mg/cu m/8 hr/day, for 1 yr, had no pathological alterations in liver morphology, but increased levels of liver cytochrome P450, cytochrome B5, nicotinamide adenine dinucleotide phosphate cytochrome C reductase, aminopyrine N-demethylase, and aniline hydroxylase. o-Xylene also increased food and water consumption and relative liver wt. Mice were exposed to 0 or 115 ppm o-xylene for 4 hr, 3 times per day on day 6 to day 15 of gestation, and the dams were killed on day 18. There was evidence of delayed weight gain and skeletal ossification in the fetuses of exposed animals. When rabbits were exposed to 0 or 115 ppm o-xylene 24 hr/day from day 7 to day 20 of gestation, no maternal toxicity or incidence of delayed development was observed in the exposed group. None of the isomers nor unspecified xylene was mutagenic to Salmonella typhimurium TA1535, TA1537, TA98, TA100, UTH 8413 or UTH8414 in the presence or absence of a metabolic activation. None of the xylene isomers induced micronuclei in the bone marrow of male mice after two ip administrations of 105-650 mg/kg body weight at a 24-hr interval, but they did, however, enhance the induction of micronuclei by toluene. ECOTOXICITY STUDIES: The xylene isomers have a similar degree of toxicity as mixed xylenes to estuarine/marine invertebrates. For o-xylene, acute toxicity values range from the 96-hour embryo lethality EC50 value of 4.1 mg/L in sea urchin eggs, to the 48-hour LC50 value of 24.7 mg/L in brine shrimp. Results of these studies indicate that o-xylene is slightly to moderately toxic to estuarine/marine invertebrates on an acute basis.
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