Evaluation of the developmental toxicity of methacrylamide and N,N '-methylenebisacrylamide in Swiss mice

Timed-pregnant CD-1 outbred albino Swiss mice received either methacrylamid e (MAC; 0, 60, 120, or 180 mg/kg/day) or N,N'-methylenebisacrylamide (BAC; 0, 3, 10, or 30 mg/kg/day) po in distilled water on gestational days (GD) 6 through 17. Maternal clinical status was monitored daily. At termination ( GD 17), confirmed-pregnant females (27-30 per group, MAC; 24-25 per group, BAG) were evaluated for clinical status and gestational outcome; live fetus es were examined for external, visceral, and skeletal malformations. For MA C, no treatment-related maternal mortality was observed. Maternal body weig ht on GD 17, maternal weight gain during treatment and gestation, and corre cted maternal weight gain were reduced at the high dose. Relative maternal food and water intake was not adversely affected; neurotoxicity was not obs erved. Relative maternal liver weight was increased at greater than or equa l to 120 mg/kg/day; gravid uterine weight was decreased at 180 mg/kg/day. T he maternal no-observed adverse effect level (NOAEL) was 60 mg/kg/day. The NOAEL for developmental toxicity was also 60 mg/kg/day. At greater than or equal to 120 mg/kg/day, mean fetal body weight was reduced. At 180 mg/kg/da y, increased postimplantation death per litter was observed. Morphological development was not affected. The maternal NOAEL for BAC was 10 mg/kg/day. At 30 mg/kg/day, decreased maternal body weight on GD 17, maternal body wei ght change during treatment and gestation, corrected maternal body weight, and gravid uterine weight were observed. Relative maternal liver weight inc reased at 30 mg/kg/day. The developmental NOAEL was 3 mg/kg/day BAG. Mean f etal body weight was reduced at 30 mg/kg/day. At greater than or equal to 1 0 mg/kg/day, an increased incidence of fetal variations (extra rib) was obs erved, although fetal malformation rate was unaffected. MAC and BAC were no t teratogenic to Swiss mice at the doses tested. BAC was more potent than M AC in causing adverse maternal and developmental effects. (C) 1998 Society of Toxicology.