Effects of lactational administration of acrylamide on rat dams and offspring.

We duplicated the study design of Husain et al. (Ind Health 1987; 25:19-28) to determine whether maternal exposure to acrylamide monomer (AM) resulted in offspring neurotoxicity. Wistar rat dams with litters (15/group) were gavaged with AM in saline at 0 or 25.0 mg/kg/d throughout lactation (pnd 0-21). Maternal feed and water consumption, body weights (BW), and Functional Observational Battery (FOB) were recorded. At weaning (pnd 21), maternal sciatic nerves were examined histologically. Male offspring were retained until pnd 91, with BW and grip strength evaluations. Dosed dams exhibited progressive toxicity, including mortality (two), severely reduced feed and water consumption, BW, and BW gain, and behavioral neurotoxicity (with no sciatic nerve pathology). Nursing offspring at 25.0 mg/kg/d exhibited increased mortality and reduced BW associated with little/no milk in stomachs. Postwean males at 25.0 mg/kg/d exhibited normal BW gain and increasing grip strength over time. Therefore, AM caused maternal toxicity; offspring effects during lactation were consistent with inanition from maternal toxicity. Postwean males exhibited recovery with no signs of AM-mediated toxicity. These results do not support the conclusions of Husain et al.

Teratogenic evaluation of epichlorohydrin in the mouse and rat and glycidol in the mouse.

Pregnant outbred albino rats (CD) and mice (CD-1) were given epichlorohydrin by gastric intubation on d 6-15 of gestation. The rats were killed on d 21 (d 18 for mice) and the offspring checked for gross, visceral, and skeletal malformations. Epichlorohydrin caused a significant reduction in the weight gain of pregnant rats at 80 mg/kg.d as compared with the control group treated only with the vehicle. However, there was no evidence of teratogenicity in the rat fetuses even at a dose level (160 mg/kg.d) that caused the death of some of the treated dams. Epichlorohydrin also did not produce a statistically significant increase in the average percent of malformed mouse fetuses, even at 160 mg/kg.d, a dose that killed 3 of 32 treated dams. The 120 and 160 mg/kg.d levels did cause a significant (p less than 0.05) reduction in the average fetal weight as compared with controls. In addition, the 120 mg/kg.d dose produced the statistically significantly increase in the liver weight of the pregnant mouse. These observations indicate that the 120 and 160 mg/kg.d dose levels were toxic toward the dams and their unborn offspring. In a similar mouse study, glycidol showed no evidence of teratogenicity. There was a significant increase in the number of stunted fetuses at 200 mg/kg.d, but all of these were present in a single litter. Further, the same dose killed 5 of 30 dams.