© 1995 Oxford University Press
research-article |
Oncogenic Potential of Inhaled Hydrazine in the Nose of Rats and Hamsters after 1 or 10 1-hr Exposures
,2,3
*Mantech Environmental Technology, Inc. Dayton, Ohio 45421
Toxicology Division, Armstrong Laboratory Wright-Patterson Air Force Base, Ohio 45433
Toxic Hazards Research Unit Wright-Patterson Air Force Base, Ohio 45433
Received September 8, 1994; accepted January 24, 1995
Hydrazine (N2H4) is used as a fuel for missiles and standby power systems of operational military aircraft. Maintenance of missiles and aircraft may result in accidental human exposure to high concentrations for brief periods of time. The purposes of this study were to assess the oncogenic potential of N2H4 in rats and male hamsters exposed to a high concentration of N2H4 for repeated short exposures and to investigate the relationships of acute and subchronic effects of N2H4 to nasal tumorigenesis. In Phase 1 (acute and subchronic) and Phase 2 (lifetime) experiments, groups of male and female Fischer 344 rats and male Syrian golden hamsters were exposed by inhalation to 0,75 (Phase 2 only), or 750 ppm N for 1 (acute) or 10 (subchronic) 1-hr weekly exposures. Rodents were euthanized 24 hr after exposures 1 and 10 and 24 to 30 months poststudy initiation. Significant reductions in body weight were observed in N2H4-treated rodents compared to controls during the exposure interval. No hydrazine-induced mortality was detected. Histopathologlc examination after the acute and subchronic exposures revealed degeneration and necrosis of transi tional, respiratory, and olfactory epithelia in the anterior nose and, in rats exposed subchronically, squamous metaplasia of the transitional epithelium. Minimal to mild rhinitis resulted from N exposures. Apoptosis was observed in olfactory and squamous metaplastic transitional epithelium. Lesions occurred at sites reportedly having high air-flow and generally appeared to be more severe In the anterior portion of the nose. By 24 months, the squamous metaplastic transitional epithelium reverted back to normal-appearing transitional epithelium. By 24+ months, low incidences (sexes combined) of hyperplasia (5/194 2.6%) and neoplasia (11/194 5.7%) were detected, principally in the transitional epithe hum of the 750 ppm N2H4-treated rats. A similar incidence of hyperplasia (2/94 2%) and neoplasia (5/94 5.3%) was detected in the high-exposure group of hamsters. The location and type of N2H4-induced proliferative lesions were similar to those reported in a chronic N2H4-exposure study (5.0 ppm x 6 hr/day x 5 days/week for 1 year) conducted in our laboratory, but the chronic study had much higher incidences (rats, sexes combined: hyperplasia 15.5% vs 2.6% and polypoid adenoma 44.6% vs 5.2%). The product (CD) of concentration x time was the same (7500 ppm hours) for the high-dose groups for both studies, but the duration of exposure was 150x longer and the concentration was 150x lower in the chronic study. These comparisons suggest that the duration of exposure is a more significant factor than concentration in N2H4-induced nasal tumorigenesis.