ABSTRACT
The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and two structurally related compounds, phenoxyacetic acid and 2,4,5-trichlorophenol, were suspended in a 1:1 solution of honey:water and administered by gavage to pregnant mice on one of gestation days 8-15 (copulation plug day = day 1) or on three consecutive days (7-9, 10-12, or 13-15). Doses were 800-900 mg/kg for single and 250-300 mg/kg/day for multiple treatments. With the exception of 2,4,5-trichlorophenol treatment on day 14, only 2,4,5-T treatment significantly increased prenatal mortality, and only 2,4,5-T was associated with decreased fetal weight when comparisons were made with the solvent controls. Although low incidences were seen in all treatment groups, only 2,4,5-T significantly increased cleft palate or other gross malformations. Significant skeletal, visceral or histopathological defects were not observed. These results indicate that both the carboxyl group and chlorination of the aromatic ring are essential for an unambiguous teratogenic response.
Subject(s)
2,4,5-Trichlorophenoxyacetic Acid/toxicity , Chlorophenols/toxicity , Fetus/drug effects , Glycolates/toxicity , Phenoxyacetates/toxicity , Abnormalities, Drug-Induced , Animals , Body Weight/drug effects , Cleft Palate/chemically induced , Female , Fetal Death/chemically induced , Gestational Age , Herbicides/toxicity , Mice , PregnancySubject(s)
Arsenates/toxicity , Arsenic/toxicity , Teratogens , Abnormalities, Drug-Induced/pathology , Administration, Oral , Animals , Arsenates/administration & dosage , Body Weight/drug effects , Female , Fetal Death/chemically induced , Fetus/drug effects , Fetus/physiology , Injections, Intraperitoneal , Maternal-Fetal Exchange , Mice , Pregnancy , Time FactorsABSTRACT
Initial experiments involving mouse development employed single IP injections of 45 mg/kg sodium arsenate on one of days 6-12 of gestation and produced a spectrum of developmental defects. Embryotoxicity was indicated by high prenatal mortality and decreased fetal weights. A chelating agent, 2,3-dimercaptopropanol (BAL), was then employed in an attempt to alleviate the adverse effects of prenatal arsenate. BAL was administered 4 hr before, concurrently with, or 4 hr after arsenate. All BAL treatments diminished arsenate-induced gross malformations and growth retardation; the concurrent treatment alleviated skeletal malformation. Injection of rats IP with arsenate has also been reported to result in teratogenicity, including renal agenesis. Further reports indicated that 40 mg/kg arsenate administered to mice by gavage on days 9-11 increased prenatal mortality, reduced fetal weights, and was associated with minor malformations. According to our recent work, however, single oral doses of arsenate must be around 120 mg/kg to cause prenatal toxicity. Multiple doses of 60 mg/kg on 3 days had little effect. Sodium arsenite has also been found to be fetotoxic and teratogenic. Such effects were seen at IP doses of 10-12 mg/kg.
