Differential hepatotoxicity and cytochrome P450 responses of Fischer-344 rats to the three isomers of dichlorobenzene
The acute hepatotoxicity and response of hepatic cytochrome P450 to treatment with the three isomers of dichlorobenzene (DCB) have been investigated. The objectives were to estimate the onset of toxicity and to further elucidate the role of cytochrome P450 in the metabolism and toxicity of these compounds. In a study design employing one animal per dose level, Fischer-344 rats were gavaged with up to 25 different dosages, then evaluated 24 h later. Hepatic necrosis, serum alanine aminotransferase, and serum aspartate aminotransferase exhibited similar patterns demonstrating that ortho-DCB (o-DCB) was the most toxic in terms of both earliest onset and degree of response at higher dosages. For these three endpoints, meta-DCB (m-DCB) exhibited a lesser toxicity. Para-DCB (p-DCB) did not cause changes in these three endpoints, but hepatic degenerative changes were found. Total hepatic cytochrome P450 responses were also different after treatment with each isomer. The o-DCB produced a dose-dependent decrease in P450 beginning at dosages lower than the onset of necrosis and appeared to be a suicide substrate for P450. The m-DCB treatment increased P450 at dosages below the onset of necrosis and decreased P450 at higher dosages, with the decline preceding the onset of hepatocyte death.
- Research Organization:
- Health Effects Research Lab., Research Triangle Park, NC (United States). Environmental Toxicology Div.
- OSTI ID:
- 6384649
- Report Number(s):
- PB-93-175719/XAB; EPA-600/J-93/102
- Resource Relation:
- Other Information: Pub. in Jnl. of Biochemical Toxicology, Vol. 7, No. 4, 257-264(Nov 1992)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZENE
TOXICITY
DEATH
DOSE-RESPONSE RELATIONSHIPS
ISOMERS
LIVER
METABOLISM
NECROSIS
PROBABILISTIC ESTIMATION
PRODUCTION
RATS
SPECIFICITY
ANIMALS
AROMATICS
BODY
DIGESTIVE SYSTEM
GLANDS
HYDROCARBONS
MAMMALS
ORGANIC COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology