Polyoxyethylene sorbitan monolaurate is widely used as an emulsifier or solubilizer in a variety of foods, cosmetics and other commercial products. In addition. TW20 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 TW20, and because of its use as a vehicle in laboratory animal studies. TW20 was evaluated for potential developmental toxicity.
Timed-mated Sprague-Dawley-derived (CD) rats (24-25 per group) were exposed to 0, 500 or 5000 mg/kg/day of TW20. Aqueous solutions were delivered by gavage in a volume of 5 ml/kg of body weight on gestational days (gd) 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 22-24 pregnancies per group were confirmed. Signs of toxicity for individual animals during the in-life phase of the study were limited to an apparent increase in the proportion of females in both treated groups experiencing transient weight loss (greater than 5 grams per dam) between gd 6 and 7. Regional hair loss (alopecia) was observed in a few TW20 exposed females in both dose groups. Neither of these findings was indicative of compromised maternal health.
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 gestation (absolute or corrected). Maternal weight gain during treatment was decreased by 14% at 5000 mg/kg/day relative to the vehicle control group, but no effect was noted at 500 mg/kg/day. There were no treatment-related effects upon the following maternal organ weights: gravid uterine weight (absolute), liver weight (absolute or relative), kidney weight (absolute or relative), and heart weight (absolute or relative). Maternal relative food intake was comparable among treatment groups throughout gestation. Maternal water intake was comparable across groups during the pre- and post-treatment periods, but was elevated by 14% during treatment at 5000 mg/kg/day relative to the vehicle control group.
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 5000 mg/kg/day (based upon a 14% decrease in weight gain during treatment) and the maternal no observed adverse effect level was 500 mg/kg/day TW20 administered to rats by gavage on gd 6 through 15. No adverse effects of TW20 upon prenatal development were noted in this study. Thus, the developmental NOAEL was greater than 5000 mg/kg/day.