Chronic inhalation exposures of Fischer 344 rats to 1,6-hexamethylene diisocyanate did not reveal a carcinogenic potential.

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.

Twenty-first century approaches to toxicity testing, biomonitoring, and risk assessment: perspectives from the global chemical industry.

The International Council of Chemical Associations' Long-Range Research Initiative (ICCA-LRI) sponsored a workshop, titled Twenty-First Century Approaches to Toxicity Testing, Biomonitoring, and Risk Assessment, on 16 and 17 June 2008 in Amsterdam, The Netherlands. The workshop focused on interpretation of data from the new technologies for toxicity testing and biomonitoring, and on understanding the relevance of the new data for assessment of human health risks. Workshop participants articulated their concerns that scientific approaches for interpreting and understanding the emerging data in a biologically relevant context lag behind the rapid advancements in the new technologies. Research will be needed to mitigate these lags and to develop approaches for communicating the information, even in a context of uncertainty. A collaborative, coordinated, and sustained research effort is necessary to modernize risk assessment and to significantly reduce current reliance on animal testing. In essence, this workshop was a call to action to bring together the intellectual and financial resources necessary to harness the potential of these new technologies towards improved public health decision making. Without investment in the science of interpretation, it will be difficult to realize the potential that the advanced technologies offer to modernize toxicity testing, exposure science, and risk assessment.