Inhalation toxicity of 1,6-hexamethylene diisocyanate homopolymers (HDI-ICand HDI-BT): Results of subacute and subchronic repeated inhalation exposure studies

This article addresses results of two 13-wk inhalation toxicity studies in Wistar rats with aerosolized 1,6-hexamethylene diisocyanate (HDI) homopolym ers using either the isocyanurate (HDI-IC) type or biuret (HDI-BT) type. Gr oups of 10 rats/sex/level were exposed nose-only to breathing zone concentr ations of 0.5, 3.3, and 26.4 mg HDI-IC/m(3) or 0.4, 3.4, and 21.0 mg HDI-BT /m(3) (MMAD = 1.4-3.3 mum). The exposure regimen was 6 h/day, 5 days/wk for 13 wk. Two control groups were used in each study; one was exposed to filt ered air, and the other to the vehicle acetone. In subacute pilot studies, groups of rats were exposed under identical conditions for 3 consecutive we eks using concentrations of approximately 4, 15-18, and 77-90 mg homopolyme r/m(3). All studies demonstrated that adverse effects were caused by irrita tion-related responses occurring predominantly in the lower respiratory tra ct. Following subchronic exposure, compound-related effects were found only at the highest concentrations used and were confined to mild respiratory d istress, marginally decreased body weights, and increased lung weights. Hem atological evaluation showed a marginal increase in leukocyte counts. Pulmo nary function testing revealed minimal changes indicative of increases in f unctional residual capacity and total lung capacity but without evidence of increased bronchial hyperreactivity to acetylcholine aerosol. Histopatholo gy demonstrated an increased recruitment of alveolar macrophages, focal int erstitial fibrosis with round-cell infiltrations, and bronchiolo-alveolar p roliferations at the high-level exposure groups. The no-observable-adverse- effect levels (NOAELs) of both the 3- and 13-wk studies were in the range o f 3- 4 mg/m(3). Appreciable differences between the two types of polyisocya nates were not observed.