Metabolism of the arylamide herbicide propanil. II. Effects of propanil and its derivatives on hepatic microsomal drug-metabolizing enzymes in the rat.
Propanil (3,4-dichloropropionanilide) is an arylamide herbicide that has been reported to be contaminated with the cytochrome P450 enzyme inducers 3,3',4,4'-tetrachloroazobenzene (TCAB) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB), which are structural analogs of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We determined if treatment of rats with TCAB, TCAOB, propanil, 3,4-dichloroaniline, TCDD, or phenobarbital induced the hepatic microsomal metabolism of propanil and 3,4-dichloroaniline. Acylamidase-catalyzed hydrolysis of propanil to 3,4-dichloroaniline was not induced by any of the pretreatments; however, hydroxylation of propanil at the 2'-position was induced by TCDD, TCAB, TCAOB, propanil, and 3,4-dichloroaniline pretreatments. Ring- and N-hydroxylations of 3,4-dichloroaniline were induced by TCDD, TCAB, TCAOB, and 3,4-dichloroaniline pretreatments. Microsomal 7-ethoxyresorufin-O-deethylase (EROD) and 7-benzoxyresorufin-O-dealkylase (BROD) activities and electrophoretic mobility of microsomal proteins suggested that cytochromes P450c and P450d were induced by TCAB and TCAOB pretreatment. EROD, BROD, and 7-pentoxyresorufin-O-dealkylase activities were slightly increased in microsomes from propanil- and 3,4-dichloroaniline-pretreated rats, which suggests that these compounds may be weak inducers of cytochrome P450 isozymes.
McMillan
D C
DC
National Center for Toxicological Research, Jefferson, Arkansas 72079.
Leakey
J E
JE
Arlotto
M P
MP
McMillan
J M
JM
Hinson
J A
JA
D000813:Anilides / Q000633:toxicity*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology; D002722:Chlorobenzenes / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011411:Propanil / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D000813:Anilides; D000814:Aniline Compounds; D001391:Azo Compounds; D002722:Chlorobenzenes; D000072317:Polychlorinated Dibenzodioxins; C013279:3,4,3',4'-tetrachloroazobenzene; C014464:3,4-dichloroaniline; C013280:3,4,3',4'-tetrachloroazoxybenzene; D011411:Propanil