Mutagenicity of 4,4'-methylenedianiline derivatives in the Salmonella histidine reversion assay.
4,4'-Methylenedianiline and its derivatives were assayed for mutagenicity in the Salmonella/microsomal mutagenicity assay develop by Ames. A specificity to revert strain TA98 suggests a mechanism of frameshift mutagenesis. Liver microsomal preparations (S-9) from rats induced with phenobarbital were most effective for metabolic activation. Alkyl substitution of 4,4'-methylenedianiline did not alter its mutagenic activity; however, substitution of both positions ortho to the amino group eliminated mutagenic activity. Substitution with alkoxy-carbonyl groups eliminated mutagenic activity, whereas halogen substitution (chlorine, fluorine) enhanced the mutagenic activity. The results presented here show the use of structure-activity studies as predictive tools for the assessment of genotoxic properties of industrial chemicals.
D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D006639:Histidine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains; D012475:Salmonella / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship; D001559:Benzhydryl Compounds
D000814:Aniline Compounds; D006639:Histidine; D009153:Mutagens; C009505:4,4'-diaminodiphenylmethane; D001559:Benzhydryl Compounds