Maternal and developmental toxicity of halogenated 4 '-nitrodiphenyl ethers in mice

In an ongoing effort to delineate structure-activity relationships in the d evelopmental toxicity of diphenyl ethers, we evaluated the maternal and dev elopmental toxicity of 10 diphenyl ethers related to the herbicide nitrofen . All possible trichlorophenyl 4'-nitrophenyl ethers were evaluated, as wer e the 2,4-difluorophenyl and 2,4-dibromophenyl 4'-nitrophenyl ethers. We al so evaluated bifenox and chlomethoxyfen, which are 2,4-dichlorophenyl conge ners with meta-substituents on the 4'-nitrophenyl ring. Nitrofen (2,4-dichl orophenyl 4'-nitrophenyl ether) was included for comparison. Identity of th e halogen affected the postnatal (but not prenatal) mortality induced by 2, 4-dihalogenated 4'-nitrophenyl ethers. The presence of 3'-substituents on t he 4'-nitrophenyl ring reduced both pre- and postnatal toxicity of 2,4-dich lorinated congeners. Among chlorinated 4'-nitrophenyl congeners without met a-substituents on the nitrophenyl ring, the position of chlorine substituen ts strongly affected the congener's potential for inducing prenatal vs. pos tnatal syndromes. All congeners increased liver to body weight ratios in un mated females, but such increases were not well-correlated with either pren atal or postnatal embryotoxicity. Teratology 59:69-80, 1999, (C) 1999 Wiley -Liss, Inc.