EMBRYOTOXICITY STUDY OF MONOMERIC 4,4'-METHYLENEDIPHENYL DIISOCYANATE(MDI) AEROSOL AFTER INHALATION EXPOSURE IN WISTAR RATS

One of the uses of MDI is as an alternative to formaldehyde in the man ufacture of furniture, ifs main route of exposure to humans being by i nhalation. There have been no previous studies on the potential prenat al toxic effects of this compound. To close this gap in information, g ravid Wistar rats, Crl:(WI)BR, were exposed by whole-body inhalation t o clean air (control) and to 1, 3, and 9 mg/m(3) MDI, respectively, fo r 6 hr per day from Days 6 to 15 post conception (p.c.). Rats were kil led on Day 20 p.c. and the following results were obtained: Treatment caused a dose-dependent decrease in food consumption in all substance- treated groups during exposure, returning to normal values after cessa tion of treatment. The lung weights in the high-close group were signi ficantly increased compared to the sham-treated control animals. Treat ment did not influence any other maternal and/or fetal parameters inve stigated (maternal weight gain, number of corpora lutea, implantation sites, pre- and postimplantation loss, fecal and placental weights, gr oss and visceral anomalies, degree of ossification), although a slight but significant increase in litters with fetuses displaying asymmetri c sternebra(e) was observed after treatment with the highest dose of 9 mg/m(3). Although the relevance of an increase of this minor anomaly in closes which cause toxic effects in dams (reduced food consumption, increased lung weights) is limited and the number observed is within the limits of biological variability, a substance-induced effect in th e high-dose group cannot be excluded with certainty. Consequently, a n o embryotoxic effect level of 3 mg/m(3) was determined. (C) 1996 Socie ty of Toxicology