National Toxicology Program

Teratologic Evaluation of Ethylene oxide (CAS No. 75-21-8) in New Zealand White Rabbits

NTP Study: TER82078

ABSTRACT

Ethylene oxide (ETO), a widely used industrial chemical and gaseous sterilant, was evaluated for toxic and teratogenic effects in artificially inseminated New Zealand white (NZW) rabbits which were matched for body weight across treatment groups on gestational day (gd) 0. ETO in 5% dextrose was administered daily in a volume of 1 ml/kg of body weight on gd 6 through 14 at dosages of 0, 9, 18 or 36 mg/kg/day, iv, or on gd 6 through 9 at dosages of 0, 18 or 36 mg/kg/day, iv. Females were weighed and observed daily during treatment for clinical signs of toxicity. At sacrifice on gd 30, a total of 15 to 22 dams (i.e., confirmed-pregnant females) per treatment group 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 and examined for external, visceral and skeletal malformations.

Administration of ETO (0, 9, 18 or 36 mg/kg/day, iv) on gd 6-14 resulted in mortality rates of 0% (0/27), 8.3% (2/24), 4.2% (1/24) and 22.2% (6/27), for the control through high-dose groups, respectively. Measures of maternal body weight (gd 14 and 30), maternal weight gain (i.e., weight gain during gestation, weight gain during treatment and absolute weight gain) and gravid uterine weight were each decreased in a dose-related manner. Examination of uterine contents on gd 30 revealed significant dose-related increases in the percentage of resorptions, nonlive and affected fetuses per litter. Average live litter size was decreased in a dose-related manner, as was the percentage of males per litter. No evidence of a treatment-related teratogenic effect observed, even at dosages which produced maternal and fetal toxicity.

Maternal toxicity related to ETO (0, 18 or 36 mg/kg/day, iv) administered on gd 6-9 was limited to localized inflammation at the injection site for 1/23 confirmed-pregnant females in the high-dose group. Maternal weight gain during treatment and during gestation were reduced in a dose-related manner, but absolute maternal weight gain was not affected. At sacrifice on gd 30, examination of the uterine contents failed to reveal any evidence of a fetotoxic or teratogenic effect.

In conclusion, no evidence for a teratogenic effect of ETO was observed when the compound was administered intravenously to NZW rabbits on gd 6-14 or gd 6-9 of gestation.

Report Date: April 18, 1983

NTIS# PB83-242016

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