Inhalation toxicity of 1,6-hexamethylene diisocyanate homopolymers (HDI-IC and 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) homopolymers using either the isocyanurate (HDI-IC) type or biuret (HDI-BT) type. Groups of 10 rats/sex/level were exposed nose-only to breathing zone concentrations 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 microm). 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 filtered air, and the other to the vehicle acetone. In subacute pilot studies, groups of rats were exposed under identical conditions for 3 consecutive weeks using concentrations of approximately 4, 15-18, and 77-90 mg homopolymer/m(3). All studies demonstrated that adverse effects were caused by irritation-related responses occurring predominantly in the lower respiratory tract. Following subchronic exposure, compound-related effects were found only at the highest concentrations used and were confined to mild respiratory distress, marginally decreased body weights, and increased lung weights. Hematological evaluation showed a marginal increase in leukocyte counts. Pulmonary function testing revealed minimal changes indicative of increases in functional residual capacity and total lung capacity but without evidence of increased bronchial hyperreactivity to acetylcholine aerosol. Histopathology demonstrated an increased recruitment of alveolar macrophages, focal interstitial fibrosis with round-cell infiltrations, and bronchiolo-alveolar proliferations 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 of 3-4 mg/m(3). Appreciable differences between the two types of polyisocyanates were not observed.
Pauluhn
J
J
Institute of Toxicology, BAYER AG, Building No. 514, 42096 Wuppertal, Germany. juergen.pauluhn.jp@bayer-ag.de
Mohr
U
U
D000280:Administration, Inhalation; D000336:Aerosols; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003485:Cyanates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D017953:Isocyanates; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D013047:Specific Pathogen-Free Organisms
D000336:Aerosols; D000395:Air Pollutants, Occupational; D003485:Cyanates; D017953:Isocyanates; C015262:1,6-hexamethylene diisocyanate