1,1,1-Trichloro-3,4-epoxybutane

Teratogenicity was evaluated in pregnant Charles River CD rats (25/group) orally exposed by gavage to trichlorobutylene oxide in Mazola corn oil vehicle at dose levels of 0, 10, 30, 100 or 300 mg/kg/day on gestation days (GD) 6-15. Cesarean sections were performed on GD 20. Significant differences were observed between treated and control animals in the following: increased maternal mortality (high-dose group, 14/25 died on GD 9-16), decreased weight and weight gain (high-dose group), and decreased fetal body weight (high-dose group). No significant differences were observed between treated and control animals in the following: mean number of viable or nonviable fetuses, early or late resorptions, postimplantation loss, total implantations, corpora lutea, fetal sex ratio, and number of fetuses or litters with fetal malformations.

The mutagenicity of trichlorobutylene oxide (TCBO) was evaluated in the bacteria Salmonella tester strains TA98, TA100, TA1535, TA1537 and TA1538 (Ames Test), and in the yeast Saccharomyces cerevisiae tester strain D3, both in the presence and absence of added metabolic activation by Aroclor-induced rat liver S9 fraction. Based on preliminary toxicity determinations, TCBO was tested for mutagenicity at concentrations up to 100 ul/desiccator (volume of desiccator not reported) using a desiccator assay method. TCBO caused a reproducible positive response in bacterial tester strains TA100, TA1535, and TA1537 without activation at concentrations of 25 ul/desiccator and higher and with activation in tester strains TA1535 at 10 ul/desiccator and higher and TA100 at 25 ul/desiccator and higher. TCBO did not cause a positive response in yeast tester strain D3, either with or without metabolic activation.

1,1,1-TRICHLOROBUTANE-3,4-OXIDE WAS A MODERATELY ACTIVE INHIBITOR OF EPOXIDE HYDRASE IN A SYSTEM USING CHICKEN LIVER MICROSOMES AND A RADIOMETRIC ASSAY BASED ON (3H)STYRENE OXIDE, AND USING PARTIALLY PURIFIED CHICKEN LIVER MICROSOMAL EPOXIDE HYDRASE AND A CONTINUOUS PHOTOMETRIC ASSAY BASED ON P-NITROSTYRENE OXIDE WITH HYDRATION MONITORED AT 310 NM. INHIBITION WAS GREATER AGAINST STYRENE OXIDE (KM= 1.0 MMOL) THAN AGAINST P-NITROSTYRENE OXIDE (KM= 4.2 MUMOL).