Evaluation of the Developmental Toxicity of {beta}-(3,4-Epoxycyclohexyl) ethytrimethosysilane in Fischer 344 Rats and New Zealand Whit Rabbits

Evaluation of the Developmental Toxicity of ß-(3,4-Epoxycyclohexyl)ethyltrimethoxysilanein Fischer 344 Rats and New Zealand White Rabbits. TYL, R. W.,BALLANTYNE, B., FISHER, L. C, AND FRANCE, K. A. (1988). FundamAppl Toxicol. 10, 439–452. ß-(3,4-epoxycyclohex-yl)ethyltrimethoxysilane(ECEMS, CAS No. 3388-04-3) is mutagenic in vitro and weaklycarcinogenic in mice after dermal application. Timed pregnantFischer 344 rats and New Zealand white rabbits were dosed withECEMS in corn oil by gavage on gestational days (gd) 6 through15 at doses of 0.0,0.25, 1.0, or 2.5 ml ECEMS/kg for rats and0.0,0.05,0.25, or 0.75 ml ECEMS/kg for rabbits. At terminationon gd 21 (rats) or gd 29 (rabbits), live fetuses were examinedfor external, visceral, and skeletal alterations. In rats, maternaltoxicity was observed at 1.0 and 2.5 ml/kg, as evidenced byreduced weight gain and food consumption during treatment, clinicalsigns of toxicity, reduced body weight on gd 21 (corrected forgravid uterine weight), and increased relative liver weight.There were no significant differences among groups on pre- orpostimplantation loss, fetal body weight/litter, or on the incidenceof malformations. Minimal fetal toxicity, dilated lateral cerebralventricles and reduced ossification in the forelimbs, was observedat 2.5 ml/kg. In rabbits, maternal mortality (2/20 does) andslightly (but statistically significantly) elevated maternalrelative kidney weight were observed at 0.75 ml/kg. Clinicalsigns of toxicity were observed at 0.25 and 0.75 ml/kg. Pre-and postimplantation loss, fetal body weight/litter, and theincidence of malformations were all unaffected by treatment.Minimal fetal toxicity, extra (13th) ribs and reduced ossificationin lumbar arch 4, was observed at 0.75 ml/kg ECEMS. Therefore,administration of ECEMS during organogenesis in rats and rabbitsproduced maternal toxicity at 1.0 and 2.5 ml/kg in rats andat 0.25 and 0.75 ml/kg in rabbits. Minimal fetal toxicity wasobserved at 2.5 ml/kg in rats and at 0.75 ml/kg in rabbits.No embryo-toxicity or teratogenicity was observed in eitherspecies at any dosage. The "no observable effect level" (NOEL)for maternal toxicity was 0.25 ml/kg for rats and 0.05 ml/kgfor rabbits; the NOEL for developmental toxicity was 1.0 ml7sol;kgfor rats and 0.25 ml/kg for rabbits.