Evaluation of the effect of BAL (2,3-dimercaptopropanol) on arsenite-induced teratogenesis in mice

The effect of the chelating agent dimercaprol (BAL) on the embryotoxic and teratogenic effects of arsenite (As3+) was determined. BAL (sc, 30 mg/kg) was administered to pregnant CD-1 mice, either 8 and 4 hr prior to or 4 and 8 hr after a 12-mg/kg ip dose of arsenite; other females received a single sc injection of 60 mg/kg BAL concurrently with the arsenite. Treatments were given on Gestation Day 9 or 12 (copulation plug = Day 1). Controls received sc corn oil or ip H2O, with or without arsenite or BAL. Arsenite treatment caused gross and skeletal malformations and prenatal deaths, while controls were unaffected. When BAL was given prior to arsenite on Day 9, incidences of prenatal mortality and skeletal malformation were significantly diminished, and on Day 12, BAL protected against fetocidal effects of arsenite when given concurrently with the arsenite. No other significant protective effects against arsenite toxicity were seen due to BAL; however, concurrent BAL treatment on Day 9 appeared to result in decreased fetal mortality and a decline in skeletal malformations. BAL given following arsenite on Day 9 afforded no significant protection against the arsenic, although an apparent decrease in gross and skeletal malformations was suggestive of such an effect. According to these results, BAL is unlikely to have a practical beneficial effect on the arsenite exposed conceptus, because it must be administered prior to the teratogen (or perhaps simultaneously with it) to be effective.