Toxicological Sciences 54, 431-440 (2000)
Copyright © 2000 by the Society of Toxicology
Prenatal Toxicity of Inhaled Polymeric Methylenediphenyl Diisocyanate (MDI) Aerosols in Pregnant Wistar Rats
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* BASF Department of Toxicology, Ludwigshafen/Rhein, Federal Republic of Germany;
Zeneca Central Toxicology Laboratory, Alderley Park, GB-Macclesfield, Cheshire, SK10 4TJ, United Kingdom; and
Center for Life Sciences and Toxicology, Research Triangle Institute, Research Triangle Park, North Carolina 27709
Mated Wistar rats, 25/group, were exposed to polymeric methylenediphenyl diisocyanate (MDI) aerosol of respirable size for 6 h/day, on gestational days (gd) 6 through 15, at 0, 1, 4, and 12 mg/m3. Maternal clinical signs, body weights, and feed and water consumption were measured throughout gestation. At scheduled sacrifice on gd 20, maternal body, gravid uterine, liver, and paired lung weights were documented. Corpora lutea were counted, implantation sites were identified: resorptions, dead and live fetuses, and placentas were weighed. All live fetuses were counted, sexed, weighed, and examined for external alterations; approximately 50% of the live fetuses/litter were preserved in Bouin's fixative and examined for visceral alterations, and the remaining live fetuses/litter were cleared and stained with alizarin red S and examined for ossified skeletal alterations. Maternal toxicity was observed at 12 mg/m3, including mortality (2 of 24 pregnant), damage to the respiratory tract, reduced body weights and weight gain, reduced liver and increased lung weights, and reduced gravid uterine weight (the last not statistically significantly different from the control value). Developmental toxicity was also observed at 12 mg/m3, including reduced placental and fetal body weights and an increased incidence of fetal skeletal variations and skeletal retardations. There was no evidence of maternal or developmental toxicity at 1 or 4 mg/m3. The no observed adverse effect concentration for maternal and developmental toxicity was therefore 4 mg/m3. There were no treatment-related teratogenic effects at any concentrations evaluated.
Key Words: polymeric methylenediphenyl diisocyanate; developmental toxicity; maternal toxicity; fetal skeletal variations and retardations; whole-body exposure to aerosols.