Pulmonary lesions in Wistar rats associated with chronic inhalation of 4,4'-methylene-diphenyl-diisocyanate (MDI)

Isocyanates are important primary material at the production of polyurethane plastics, varnishes and glues. Nearly 3 million tons of isocyanate are produced yearly worldwide.Isocyanate have a irritating effect on eyes and airways as well as a sensitizing effect on the respiratory tract (isocyanate asthma). Since the risks for human health resulted mainly from inhalation uptake, a long-term inhalation toxicity/carcinogenicity study sponsored by the Bundesministerium für Umwelt, Naturschutz und Reaktorsicherheit/Umweltbundesamt (FKZ 11606084) was performed. 320 female Wistar rats (Crl:[WI]BR) were allocated to 4 groups of 80 females each and exposed in 6 m³ whole body inhalation chambers on average 17 h/day, 5 day/week for upto 24 months to clean air or to 0.2, 0.7 and 2.1 mg/m³ of monomeric MDI (MMAD: 1.03-1.06) aerosol. In the following, the main histopathological findings of the carcinogenicity study are summarized with emphasis on the lungs.