Effect of tetrachlorophthalic anhydride on hepatic microsomal metabolism in rats and mice.
The capacity for induction of microsomal metabolic enzymes by tetrachlorophthalic anhydride (TCPA) was evaluated in male Sprague-Dawley rats and male CD-1 mice. The rats were orally dosed for 7 d with TCPA suspended in corn oil at 25, 100, 250, or 500 mg/kg. Following this treatment a dose-dependent reduction in the zoxazolamine paralysis time occurred over the dose range 100-500 mg/kg in the rat. No effect on the hexobarbital sleep time was observed at any test level. TCPA was found to produce statistically significant increases in hepatic aminopyrine N-demethylase, aniline hydroxylase, and cytochrome P-450 in the rat at 500 mg per kg. In addition statistically significant increases were seen in aniline hydroxylase and cytochrome P-450 at 25 mg/kg. Mice were orally dosed with TCPA for 7 d at 250, 500, or 1000 mg/kg. There was no effect in the zoxazolamine paralysis time or the hexobarbital sleep time in this species. Hepatic microsomal enzyme levels were not measured in the mouse. These results suggest that following oral dosage TCPA is a weak inducer of microsomal enzymes in the rat. A similar effect was not observed in the mouse for the parameters tested.
Ridley
W P
WP
Environmental Health Laboratory, Monsanto Agricultural Company, St. Louis, Missouri 63110.
Warren
J
J
Nair
R S
RS
D000633:Aminopyrine N-Demethylase / Q000096:biosynthesis; D000815:Aniline Hydroxylase / Q000096:biosynthesis; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010243:Paralysis / Q000139:chemically induced; D010795:Phthalic Acids / Q000494:pharmacology*; D010796:Phthalic Anhydrides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D013045:Species Specificity; D015049:Zoxazolamine / Q000494:pharmacology
D010795:Phthalic Acids; D010796:Phthalic Anhydrides; C009409:tetrachlorophthalic anhydride; D003577:Cytochrome P-450 Enzyme System; D015049:Zoxazolamine; D000815:Aniline Hydroxylase; D000633:Aminopyrine N-Demethylase