Toluene diisocyanate (TDI) airway effects and dose-responses in different animal models

Many inhalation exposure studies have been performed with toluene diisocyanate (TDI) in different animal species. Many were targeted at respiratory irritation and/or sensitisation. As there is still no broadly accepted guideline for the performance of respiratory sensitisation tests, protocols used and endpoints investigated are numerous. In this review we collected data from those respiratory sensitisation and/or irritation studies that provided threshold or dose-response information. Against this aim, and as TDI is a model substance for a respiratory sensitiser, a great number of mechanistic studies are not cited in this paper, although they were checked for relevant information. The literature data available allow the conclusion that both respiratory irritation and sensitisation may be interdependent, and both irritation and sensitisation by TDI is a threshold phenomenon. Across species, the majority of NOAECs for respiratory sensitisation are in the range of 0.005 to 0.03 ppm, whereas the LOAEC is about 0.02 to 0.4 ppm.