Acute, subacute, and subchronic inhalation toxicity studies of respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol in rats.
Short-term inhalation toxicity studies with respirable polymeric methylene diphenyl diisocyanate (polymeric MDI) aerosol were performed in rats. The 4-hr LC50 was found to be 490 mg polymeric MDI/m3 (95.5% < 4.3 microns). Exposure of (4-week-old) rats to 0, 2.2, 4.9, or 13.6 mg polymeric MDI/m3 (95% < 5 microns) for 2 weeks resulted in mortality, severe growth retardation, and elevated lung weights at 13.6 mg/m3; at 4.9 mg/m3 slight growth retardation and slightly elevated lung weights were observed. A 13-week study with 6-week-old rats exposed to 0.35, 1.4, or 7.2 mg polymeric MDI/m3 (95% < 5 microns) revealed transient growth retardation and a slightly increased number of pulmonary alveolar macrophages occasionally accompanied by increased numbers of mononuclear cells and fibroblasts in alveolar septa only at 7.2 mg/m3. In a second 2-week study with 4- or 6-week-old rats exposed to 14.1 mg polymeric MDI/m3 (95% < 5 microns), 4-week-old rats died earlier and in greater numbers than 6-week-old rats. In a second 13-week study with 6-week-old rats, using exposure concentrations of 0, 4.1, 8.4, and 12.3 mg polymeric MDI/m3 (95% < 5 microns) and including a 4-week recovery period, 12.3 mg/m3 induced mortality, growth retardation, severe respiratory distress, increased lung weights, degeneration and hyperplasia of the nasal epithelium, accumulations of macrophages in the lungs and mediastinal lymph nodes, and focal inflammatory changes in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)
Reuzel
P G
PG
TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
Kuper
C F
CF
Feron
V J
VJ
Appelman
L M
LM
Löser
E
E
D000336:Aerosols; D000395:Air Pollutants, Occupational / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006197:Hair / Q000737:chemistry; D017953:Isocyanates / Q000633:toxicity*; D007928:Lethal Dose 50; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D009296:Nasal Cavity / Q000473:pathology; D010316:Particle Size; D011140:Polyurethanes / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013997:Time Factors
D000336:Aerosols; D000395:Air Pollutants, Occupational; D017953:Isocyanates; D011140:Polyurethanes; C087867:polymeric 4,4'-diphenylmethane diisocyanate