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© 1998 Oxford University Press

research-article

Evaluation of the Developmental Toxicity of Methacrylamide and N,N'-Methylenebisacrylamide in Swiss Mice1

Julia D. George*, Catherine J. Price*, Melissa C. Marr*, Christina B. Myers*, Bernard A. Schwetz{dagger} and Jerrold J. Heindel{dagger}

*Chemistry and Life Sciences, Research Triangle Institute Post Office Box 12194, Research Triangle Park, North Carolina 27709-2194 {dagger}Developmental and Reproductive Toxicology Group, National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park North Carolina 27709

Received November 3, 1997; accepted May 19, 1998

Timed-pregnant CD-1 outbred albino Swiss mice received either methacrylamlde (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, BAC) were evaluated for clinical status and gestational outcome; live fetuses were examined for external, visceral, and skeletal malformations. For MAC, no treatment-related maternal mortality was observed. Maternal body weight on GD 17, maternal weight gain during treatment and gestation, and corrected maternal weight gain were reduced at the high dose. Relative maternal food and water intake was not adversely affected; neurotoxicity was not observed. Relative maternal liver weight was increased at a 120 mg/kg/day; gravid uterine weight was decreased at 180 mg/kg/day. The maternal no-observed adverse effect level (NOAEL) was 60 mg/kg/day. The NOAEL for developmental toxicity was also 60 mg/kg/day. At ≥ 120 mg/kg/day, mean fetal body weight was reduced. At 180 mg/kg/day, 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 weight change during treatment and gestation, corrected maternal body weight, and gravid uterine weight were observed. Relative maternal liver weight increased at 30 mg/kg/day. The developmental NOAEL was 3 mg/kg/day BAC. Mean fetal body weight was reduced at 30 mg/kg/day. At ≥ 10 mg/kg/day, an increased incidence of fetal variations (extra rib) was observed, although fetal malformation rate was unaffected. MAC and BAC were not teratogenic to Swiss mice at the doses tested. BAC was more potent than MAC in causing adverse maternal and developmental effects.

Key Words: acrylamides; developmental toxicity; teratogenicity; mice; morphological development.


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