Influence of symmetrical polychlorinated biphenyl isomers on embryo and fetal development in mice. II. Comparison of 4,4'-dichlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl, 3,3',5,5'-tetrachlorobiphenyl, and 3,3',4,4'-tetramethylbiphenyl

Abstract

Outbred albino (CD-1) mice were given the following biphenyl isomers by gavage in cottonseed oil on Days 6-15 of gestation: 4,4'-dichlorobiphenyl (DCB) at 16, 32, and 64 mg/kg/day; 3,3',4,4'-tetrachlorobiphenyl (3,4-TCB) at 1,2,4,8,16,32, and 64 mg/kg/day; 3,3',5,5'-tetrachlorobiphenyl (3,5-TCB) at 64 mg/kg/day; and 3,3',4,4'-tetramethylbiphenyl (TMB) at 64 mg/kg/day. The mice were killed on Day 18 of gestation, necropsies were performed on the dams, and the fetuses were examined for external, visceral, and skeletal malformations. Although DCB was toxic to the dams at 64 mg/kg/day, developmental toxicity was not detected. 3,4-TCB administration was followed by a significant (p less than 0.01) increase in the average percentage of malformed fetuses per litter at 4 (7.2%), 8 (9.8%), 16 (25.4%), 32 (50.0%), and 64 (75.0%) mg/kg/day versus the vehicle control group (1.1%). None of the dosages tested was lethal to any of the dams. Significant decreases in maternal weight gain were observed at 16 mg/kg/day and above; however, the differences from the control value most likely were due to significant decreases in the mean number of live fetuses per dam, as the result of reductions in the number of implants per dam, and significant increases in the incidence of resorptions. Vaginal bleeding and other evidence of abortifacient effects also were present in several dams in groups receiving 3,4-TCB at 16 mg/kg/day and above. Cleft palate and hydronephrosis (significantly increased at dosages of 4 mg/kg/day and above) were the predominant malformations detected. Thus, 3,4-TCB was found to be toxic to the conceptus at dosages of 4 mg/kg/day and above. Neither 3,5-TCB nor TMB showed indications of maternal or developmental toxicity at 64 mg/kg/day