Evaluation of the developmental toxicity of beta-(3,4-epoxycyclohexyl)ethyltrimethoxysilane in Fischer 344 rats and New Zealand white rabbits.

beta-(3,4-epoxycyclohexyl)ethyltrimethoxysilane (ECEMS, CAS No. 3388-04-3) is mutagenic in vitro and weakly carcinogenic in mice after dermal application. Timed pregnant Fischer 344 rats and New Zealand white rabbits were dosed with ECEMS in corn oil by gavage on gestational days (gd) 6 through 15 at doses of 0.0, 0.25, 1.0, or 2.5 ml ECEMS/kg for rats and 0.0, 0.05, 0.25, or 0.75 ml ECEMS/kg for rabbits. At termination on gd 21 (rats) or gd 29 (rabbits), live fetuses were examined for external, visceral, and skeletal alterations. In rats, maternal toxicity was observed at 1.0 and 2.5 ml/kg, as evidenced by reduced weight gain and food consumption during treatment, clinical signs of toxicity, reduced body weight on gd 21 (corrected for gravid uterine weight), and increased relative liver weight. There were no significant differences among groups on pre- or postimplantation loss, fetal body weight/litter, or on the incidence of malformations. Minimal fetal toxicity, dilated lateral cerebral ventricles and reduced ossification in the forelimbs, was observed at 2.5 ml/kg. In rabbits, maternal mortality (2/20 does) and slightly (but statistically significantly) elevated maternal relative kidney weight were observed at 0.75 ml/kg. Clinical signs of toxicity were observed at 0.25 and 0.75 ml/kg. Pre- and postimplantation loss, fetal body weight/litter, and the incidence of malformations were all unaffected by treatment. Minimal fetal toxicity, extra (13th) ribs and reduced ossification in lumbar arch 4, was observed at 0.75 ml/kg ECEMS. Therefore, administration of ECEMS during organogenesis in rats and rabbits produced maternal toxicity at 1.0 and 2.5 ml/kg in rats and at 0.25 and 0.75 ml/kg in rabbits. Minimal fetal toxicity was observed at 2.5 ml/kg in rats and at 0.75 ml/kg in rabbits. No embryotoxicity or teratogenicity was observed in either species at any dosage. The "no observable effect level" (NOEL) for maternal toxicity was 0.25 ml/kg for rats and 0.05 ml/kg for rabbits; the NOEL for developmental toxicity was 1.0 ml/kg for rats and 0.25 ml/kg for rabbits.