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 manufacture of furniture, its main route of exposure to humans being by inhalation. There have been no previous studies on the potential prenatal toxic effects of this compound. To close this gap in information, gravid Wistar rats, Crl:(WI)BR, were exposed by whole-body inhalation to clean air (control) and to 1, 3, and 9 mg/m3 MDI, respectively, for 6 hr per day from Days 6 to 15 post conception (p.c.). Rats were killed 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 cessation of treatment. The lung weights in the high-dose group were significantly increased compared to the sham-treated control animals. Treatment did not influence any other material and/or fetal parameters investigated (maternal weight gain, number of corpora lutea, implantation sites, pre- and postimplantation loss, fetal and placental weights, gross and visceral anomalies, degree of ossification), although a slight but significant increase in litters with fetuses displaying asymmetric sternebra(e) was observed after treatment with the highest dose of 9 mg/m3. Although the relevance of an increase of this minor anomaly in doses 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 the high-dose group cannot be excluded with certainty. Consequently, a no embryotoxic effect level of 3 mg/m3 was determined.
Buschmann
J
J
Fraunhofer Institute of Toxicology and Aerosol Research, Hannover, Germany.
Koch
W
W
Fuhst
R
R
Heinrich
U
U
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D004435:Eating / Q000187:drug effects; D005260:Female; D017953:Isocyanates / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013723:Teratogens / Q000633:toxicity*; D001559:Benzhydryl Compounds
D000336:Aerosols; D017953:Isocyanates; D013723:Teratogens; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds