The chronic toxicity and oncogenicity of inhaled toluene were assessed in Fischer-344 rats. One hundred and twenty animals of each sex were exposed for 6 hours/day, 5 days/week, for up to 24 months at concentrations of toluene in air of 0, 30, 100, or 300 ppm. The calculated time-weighted average concentrations for the 24 months of exposure were 0.0, 30.1, 99.7, and 299.0 ppm, respectively. Interim sacrifices on randomly selected animals were conducted after 6, 12 and 18 months of exposure. All surviving rats were sacrificed at 24 months. A large battery of tissues and organs from all animals in the control and 300 ppm toluene group were examined for histopathology. All animals were examined for clinical changes throughout the course of the study and selected animals were used to determine ophthalmologic, hematologic, clinical blood chemistry or urinalysis effects. There were 140 unscheduled deaths over the 2-years study. Gross pathologic examination of rats dying during the course of the study, or that were sacrificed as scheduled, did not reveal any lesions attributable to toluene exposure. Histologically, a variety of proliferative, degenerative and inflammatory lesions were observed in the control and 300 ppm toluene-exposed group. These lesions were considered unrelated to toluene exposure. The results provide no evidence that toluene causes chronic toxicity or oncogenicity in Fischer-344 rats at these concentrations.

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Rat hepatic microsomal cytochrome(s) P-450 induced by polybrominated biphenyls.

Various parameters have been measured in order to characterize the type of cytochrome(s) P-450 induced by a single ip injection of polybrominated biphenyls (PBB's), 150 mg/kg, given to female rats. The ratio of the 427/455-nm peaks in the microsomal ethylisocyanide difference spectra showed a gradual increase with time after treatment with PBB's. Inhibition studies of aryl hydrocarbon hydroxylase and ethoxycoumarin O-de-ethylase and alpha-naphthoflavone and metyrapone also showed changes in the qualitative nature of these enzymes after treatment with PBB's. Both the high- and low-affinity KM values for ethoxycoumarin O-de-ethylase decreased in magnitude from 0.240 and 0.083 micrometer at 24 hr to 0.188 and 0.042 micrometer, respectively, at 192 hr after treatment with PBB's. Sodium dodecyl sulfate-gel electrophoresis failed to demonstrate a 3-methylcholanthrene-like pattern of hemoprotein at any time after treatment with PBB's. We conclude that while PBB's have some of the properties of a mixed inducer they do not have all of the properties of both phenobarbital and 3-methylcholanthrene, and the PBB's may represent a new class of inducing agents.

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PubMedDate not supplied

Stimulation of hepatic and renal mixed-function oxidase in developing rats by polybrominated biphenyls.

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