endrin and Abnormalities--Drug-Induced

The teratogenic effects of endrin and lindane have been determined and compared to those induced by TCDD in the fetuses of C57BL/6J and DBA/2J mice after the administration of single oral doses to pregnant mice on day 12 of gestation. TCDD produced dose-dependent decreases in fetal weight, fetal thymic weight and placental weight, and dose-dependent increases in fetolethality, cleft palate formation and hydronephrosis at doses of 10-30 and 30-60 micrograms/kg body weight in C57BL/6J and DBA/2J mice, respectively. No maternal death was observed at the given doses in both strains of mice. Endrin (4.5 and 6 mg/kg body weight) and lindane (30 and 45 mg/kg body weight) produced significant decreases in fetal weight and placental weight in C57BL/6J and DBA/2J mice, and dose-dependent decreases in fetal thymic weight in C57BL/6J mice but not DBA/2J mice. Endrin and lindane caused 0-25 and 14-25% maternal deaths, respectively, at the above mentioned doses. Neither cleft plate nor hydronephrosis were induced by endrin or lindane in the two strains of mice. The results support the hypothesis that TCDD-induced cleft plate and hydronephrosis involve mechanisms that are Ah (aryl hydrocarbon) receptor mediated. However, other fetotoxic effects induced by TCDD, and the fetotoxic effects induced by endrin and lindane may involve additional unknown mechanisms that are not related to the Ah-receptor.

Topics: Abnormalities, Drug-Induced; Animals; Cleft Palate; Dose-Response Relationship, Drug; Endrin; Female; Gestational Age; Hexachlorocyclohexane; Hydronephrosis; Insecticides; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Polychlorinated Dibenzodioxins; Pregnancy

The science of teratology is discussed from a regulatory point of view. A brief history of this branch of toxicology is presented with emphasis on specific instances of the inadvertent production of birth defects in humans as a result of exposure to exogenous agents. The basic principles of teratology are elucidated as a means of understanding current test protocols and their scientific rationale. A typical, general protocol is given and some of the major shortcomings of such a bioassay are presented. Among these shortcomings are the problems of significance of fetal toxicity and lack of a postnatal component to the teratology test system. The teratogenic and/or fetotoxic potential of selected pesticides are examined with special reference to the bioassay problems alluded to. Pesticides discussed include cacodylic acid, endrin, benomyl, ETU, nitrofen, and mirex. Finally, a brief discussion of a proposed teratology screen using pregnant laboratory animals is presented.

Topics: Abnormalities, Drug-Induced; Animals; Benomyl; Cacodylic Acid; Drug Evaluation, Preclinical; Endrin; Ethylenethiourea; Female; Humans; Mirex; Pesticides; Phenyl Ethers; Pregnancy; Teratogens

Topics: 2,4-Dichlorophenoxyacetic Acid; 2,4,5-Trichlorophenoxyacetic Acid; Abnormalities, Drug-Induced; Animals; Chickens; Endrin

Topics: Abnormalities, Drug-Induced; Aldrin; Animals; Cleft Lip; Cleft Palate; Cricetinae; Dieldrin; Endrin; Eye Abnormalities; Fetus; Foot Deformities, Congenital; Mice