title: Chronic inhalation exposures of Fischer 344 rats to 1,6-hexamethylene diisocyanate did not reveal a carcinogenic potential.
abstract: The polyisocyanates of 1,6-hexamethylene diisocyanate (HDI) find widespread commercial use as components of paints and in the formulation of light-stable polyurethane coating materials. This 2-year study assessed the oncogenicity of the diisocyanate monomer HDI in male and female Fischer-344 rats exposed 6 h/day, 5 days/week to mean analytical air concentrations of 0, 0.005, 0.025, and 0.164 ppm HDI. During the in-life phase, transient eye irritation was observed in 0.164 ppm males, and a slight body weight decrease (5%) in the 0.164 ppm females during the second year of exposure. There were no exposure-related effects on mortality. Compound-related, non-neoplastic histopathologic changes were limited to the respiratory tract and changes were characterized by epithelial tissue reaction to the acute irritant properties of HDI vapor. For tissues of the nasal cavity, the major histopathologic findings were degeneration of the olfactory epithelium characterized by destruction of the epithelial architecture often with narrowing or atrophy and occasional focal erosion or ulceration. In addition, there was variable degeneration of the respiratory epithelium with hyperkeratosis of the epithelium, epithelial and mucus secretory cell hyperplasia, squamous metaplasia, chronic-active inflammation, and errosive or ulcerative changes. These tissue effects along with a statistically significant decrease in body weight of female rats demonstrated attainment of a maximum tolerated dose. There was no evidence of progression of these changes in the nasal epithelium to neoplasia nor evidence of any compound-related neoplastic lesions for any of the other tissues examined. Therefore, it is concluded that HDI did not show a carcinogenic potential in this study.
authors.affiliation: Bayer MaterialScience LLC, Pittsburgh, Pennsylvania 15205, USA. ron.shiotsuka@bayerbms.com
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Shiotsuka
authors.forename: Barry P
authors.initials: BP
authors.lastname: Stuart
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Charles
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Simon
authors.forename: Paul
authors.initials: P
authors.lastname: Malichky
authors.forename: Janet M
authors.initials: JM
authors.lastname: Mostowy
mesh_terms: D000393:Air Pollutants / Q000145:classification / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000145:classification / Q000633:toxicity*; D003485:Cyanates / Q000145:classification / Q000633:toxicity*; D005131:Eye Injuries / Q000139:chemically induced; D005260:Female; D019570:Inhalation Exposure; D007509:Irritants / Q000633:toxicity*; D017953:Isocyanates; D008136:Longevity / Q000187:drug effects; D008297:Male; D020714:Maximum Tolerated Dose; D009296:Nasal Cavity / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology; D036401:Toxicity Tests, Chronic
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D003485:Cyanates; D007509:Irritants; D017953:Isocyanates; C015262:1,6-hexamethylene diisocyanate