Ethylene chlorohydrin (2-chloroethanol), a widely used industrial chemical and reaction product of the gaseous sterilant ethylene oxide, was evaluated for toxic and teratogenic effects in timed-pregnant CD-1 mice. ECH (0, 60 or 120 mg/kg/day, intravenous) in 5% dextrose was administered daily in a volume of 1 mL/kg of body weight on gestational days 4-6, 6-8, 8-10 or 10-12. Plug-positive females were matched by body weight across treatment groups prior to the initiation of dosing and weighed daily during treatment. At sacrifice on gd 17 a total of 34-54 dams (i.e., confirmed-pregnant females) per treatment group from each exposure period were evaluated. The gravid uterus of each dam was weighed and the number of implantation sites and live, dead or resorbed fetuses were recorded. All live fetuses were weighed, sexed and examined for external, visceral and skeletal malformations. Administration of the low dose of ECH (60 mg/kg/day) did not result in any statistically significant expression of maternal toxicity, regardless of the period of administration. Evidence of embryotoxicity in the low-dose group was observed only following exposure to ECH on gd 8-10, a treatment which significantly decreased the average fetal body weight per litter. No statistically significant change in the incidence of malformed fetuses per litter was observed for any exposure period at the low dose.
Administration of the high dose of ECH (120 mg/kg/day) resulted in mortality rates of 0%, 8%, 12.3% and 15.6% among plug-positive females treated on gd 4-6, 6-8, 8-10 and 10-12, respectively. The high-dose group also exhibited a significant dose-related reduction in maternal weight gain during treatment for each of the exposure periods. In addition, dams treated on gd 8-10 or 10-12 showed decreased gestational weight gain, as well as decreased gravid uterine weight, but no decrease in absolute maternal weight gain. ECH (120 mg/kg/day) produced dose-related signs of embryotoxicity including a significant reduction in average fetal body weight per litter for each exposure period. Litters from females exposed to the high dose on gd 4-6, 8-10 or 10-12 also exhibited a significant increase in the percentage per litter of resorbed, nonlive and affected fetuses. A significant increase in the percentage of malformed fetuses per litter was observed in only one exposure group (i.e., ECH, 120 mg/kg/day on gd 8-10) which exhibited 2.3% malformed fetuses per litter as compared to 0.2% malformed fetuses per litter for the vehicle control group. Further examination of the data indicated that this effect was statistically significant only for one of four study replicates, in which the mortality rate for treated females was 46.7%.
In conclusion, ECH (0, 60 or 120 mg/kg/day) administered to timed pregnant CD-l mice on gd 4-6, 6-8, 8-10 or 10-12 was associated in a dose-related manner with maternal and fetal toxicity (reduced body weight). An increase in the incidence of malformed fetuses was seen only at one exposure period (gd 8-10) and at a dose of ECH (120 mg/kg/day) which was associated with increased maternal mortality.