Polyoxyethylene sorbitan monooleate is widely used as an emulsifier or solubilizer in a variety of foods, cosmetics and other commercial Products. In addition, TW80 in water has been used as a vehicle for the delivery of other chemical agents to pregnant laboratory animals by the oral route of administration (eg. by gavage or in the drinking water). Based upon the large population of pregnant women potentially exposed to TW80, and because of its use as a vehicle in laboratory animal studies, TW80 was evaluated for potential developmental toxicity.
Timed-mated Sprague-Dawley-derived (CD) rats (25 per group) were exposed to 0, 500 or 5000 mg/kg/day of TW80. Aqueous soluti ons were delivered by gavage in a volume of 5 ml/kg of body weight on gestational days 6 through 15. At termination (gd 20), the uterus was removed and examined to determine pregnancy status, and to evaluate the number of resorptions, and dead or live fetuses. Dead or live fetuses were weighed, and live fetuses were examined for external, visceral and skeletal defects.
All treated females survived to scheduled necropsy and 19-23 pregnancies per group were confirmed. No dose-related signs of toxicity were observed for individual animals during the in-life phase of the study or at scheduled necropsy.
Average maternal body weight (gd 0, 3, 6, 9, 12, 15, 18, or 20) did not differ among treatment groups, nor was there a treatment related change in maternal weight gain during treatment or gestation (absolute or corrected). There were no treatment-related effects upon the following maternal organ weights: gravid weight (absolute), kidney weight (absolute or relative), and heart weight (absolute or relative). Relative maternal liver weight (% body weight on gd 20 or % corrected body weight) was elevated in both TW80 groups and absolute liver wei ght was elevated at 500 mg/kg/day. Maternal food intake was comparable across groups during the pre- and post-treatment periods, but was decreased by 14% during the first 3 days of treatment at 5000 mg/kg/day relative to the vehicle control group. Maternal relative water intake was comparable among treatment groups throughout gestation.
No differences among groups were noted for the number of corpora lutea per dam, the number of implantation sites per dam or the percent preimplantation loss per litter. No adverse effects were noted on the growth, viability or morphological development of the conceptuses.
In conclusion, the maternal lowest observed adverse effect level was 500 mg/kg/day (based upon an increase in maternal relative liver weight). No definitive adverse effects of TW80 upon prenatal development were noted in this study. Thus, the developmental no observed adverse effect level was greater than 5000 mg/kg/day.