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.

Nasal epithelial repair and remodeling in physical injury, infection, and inflammatory diseases

“…They saw active epithelial migration and proliferation in the injured area, followed by hyperplasia and differentiation into fully restored epithelium during 14 days after injury. Recently, Shiotsuka et al [10] studied the toxicity of 1,6-hexamethylene diisocyanate (HDI) in rats. Recently, Shiotsuka et al [10] studied the toxicity of 1,6-hexamethylene diisocyanate (HDI) in rats.…”

Comparative Study of Aromatic and Cycloaliphatic Isocyanate Effects on Physico-Chemical Properties of Bio-Based Polyurethane Acrylate Coatings

“…Studies of cancer risk have revealed that TDI and MDI are linked to cancer risk with the ability to bind the DNA and lead to genotoxicity [ 18 ]. Meanwhile, HDI and IPDI are safer and have been testified as not associated with carcinogenic effects [ 19 , 20 ].…”

Case Report: Two Cases of Salivary Duct Carcinoma in Workers With a History of Chromate Exposure

“…Apart from the chromate in the CARC (topcoat of the metal surface), HDI is considered the most toxic ingredient ( 50 ). HDI is a known respiratory sensitizer, but has not been classified as a carcinogen and is therefore unlikely to have contributed to the occurrence of SDC ( 51 ). Furthermore, our first patient was exposed to fumes from soldering when he worked as a plumber.…”