MATERNAL AND DEVELOPMENTAL TOXICITY OF POLYCHLORINATED DIPHENYL ETHERS (PCDES) IN SWISS-WEBSTER MICE AND SPRAGUE-DAWLEY RATS

Polychlorinated diphenyl ethers (PCDEs) are industrial byproducts foun d in many ecosystems at low levels. PCDEs are not markedly toxic to ad ult rodents, but their developmental toxicity has not previously been examined. We evaluated the maternal and perinatal toxicity of nine PCD E congeners to outbred mice when compounds were administered from gest ation day (GD) 6 through GD 15.2,2',4,4',5,6'-hexaCDE and 2,3',4',6-te traCDE decreased the number of pups born per female mated and the numb er of pups surviving per litter born. 2,2',4,4',5,5'-hexaCDE and 2,2', 4,5,6'-petaCDE decreased the number of litters born per female mated, without decreasing postnatal survival. The other PCDEs did not decreas e survival either pre- or postnatally. None of the PCDEs caused absenc e of Harderian glands in surviving offspring at the doses administered . Neither induction of cytochromes P450 nor tissue residues of individ ual congeners correlated well with developmental toxicity. Three PCDEs were also evaluated in outbred (Sprague-Dawley) rats: 2,2',4,5,6'-pen taCDE and 2,3',4',6-tetraCDE, because of their toxicity to mice; 2,2', 4,3',5,5'-hexaCDE, because it should exhibit PCB-like toxicity. Each c ongener was administered at three dose levels from GD 6 through GD 15. 2,2',4,5,6'-pentaCDE decreased the number of litters born at 100 mg/kg /day, and the survival of pups in litters carried to term, at both 50 and 100 mg/kg per day. Postnatal weight gain was also reduced. In cont rast to its action in mice, 2,3',4',6-tetraCDE decreased neither the n umbers of litters born nor postnatal survival of rat offspring, but di d suppress postnatal weight gain at least through PD 5. As in mice, in duction of cytochromes P450 was not well correlated with the developme ntal toxicity of individual congeners. (C) 1997 Elsevier Science Irela nd Ltd.