Genotoxicity and effects on rat liver drug-metabolizing enzymes by possible substitutes for 4,4'-methylene bis(2-chloroaniline).
The mutagenic properties of Ethacure 300, Cyanacure and Polacure 740M, all possible substitutes for the industrial carcinogen, 4,4'-methylene bis(2-chloroaniline), have been determined in Salmonella typhimurium strains TA100, TA98, TA1535 and TA1537. These data have been compared with the effects of these chemicals on ethoxyresorufin O-deethylase (EROD) activity and aldrin epoxidase (AE) activity in rat liver. Ethacure 300 was clearly positive in both TA100 and TA98 bacterial strains, while Cyanacure was positive only in TA100. Polacure 740M was negative in all strains. Ethacure 300 caused a 28-fold induction of EROD while Cyanacure caused a doubling. Polacure 740M was without effect. Neither Ethacure 300 nor Cyanacure affected AE, while Polacure 740M caused an increase at only the lower dose tested. Thus there was excellent correlation between mutagenicity and EROD induction. A similar correlation was noted for six other structurally related compounds giving support to the contention that the ability of a chemical to induce EROD bears some relationship to its carcinogenic potential.
Wu
K
K
National Institute of Occupational Health and Safety, University of Sydney, NSW, Australia.
Bonin
A M
AM
Leslie
C L
CL
Baker
R S
RS
Stacey
N H
NH
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D066298:In Vitro Techniques; D008753:Methylenebis(chloroaniline) / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D010088:Oxidoreductases / Q000378:metabolism; D010655:Phenylenediamines / Q000494:pharmacology*; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship; D062366:para-Aminobenzoates
D000814:Aniline Compounds; D001559:Benzhydryl Compounds; D009153:Mutagens; D010655:Phenylenediamines; D011409:Propylene Glycols; D062366:para-Aminobenzoates; C061701:Ethacure 300; D008753:Methylenebis(chloroaniline); C061702:Cyanacure; C061700:propane-1,3-diyl bis(4-aminobenzoate); D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; C019647:aldrin epoxidase; D019363:Cytochrome P-450 CYP1A1; D010129:4-Aminobenzoic Acid