Role of structure in diphenyl ether teratogenesis

The fetotoxicity of nitrofen and 5 analogous diphenyl ethers was compared in mice, using survival on postnatal day 5 to evaluate prenatal and perinatal toxicity. The effect of each chemical on the Harderian gland weight of surviving pups was also assessed, since decreased Harderian gland weight is seen in nitrofen-exposed pups at levels of treatment that do not cause mortality. All treatments were percutaneous. 2,4,5-Trichlorophenyl 4′-nitrophenyl ether was significantly more fetotoxic than nitrofen, but 2,4,6-trichlorophenyl 4′-nitrophenyl ether (CNP) was not fetotoxic at the doses used. Neither of the 2 monochlorinated 4′-nitrophenyl ethers nor the unchlorinated 4′-nitrophenyl ether were fetotoxic at the doses tested. Absent Harderian glands resulted only from exposure to nitrofen (71% of litters) or to 2,4,5-trichlorophenyl 4′-nitrophenyl ether (22% of litters), which were also the only compounds to decrease Harderian gland weight significantly.