Emergency and Continuous Exposure Guidance Levels for Selected Submarine Contaminants: VOLUME 1 by National Research Council of the National Academies

Author:National Research Council of the National Academies
Language: eng
Format: epub
Tags: Environment and Environmental Studies : Environmental Health and Safety
Publisher: NATIONAL ACADEMY PRESS
Published: 2007-03-12T00:00:00+00:00

Chronic Toxicity

MacEwen et al. (1981) and Vernot et al. (1985) published the results of a hydrazine inhalation study conducted in male and female Fischer 344 rats, female C57BL/6 mice, male Syrian hamsters, and 6-month-old male and female beagle dogs.

Groups of 100 rats were exposed to hydrazine at 0.05, 0.25, 1.0, or 5.0 ppm for 6 h per day, 5 days per week for 52 weeks and were maintained for an additional 18 months post-exposure. Rat mortality at termination of the study was similar in all groups. Body weights of rats were decreased compared with controls; the most significant effect was observed in male rats exposed at 5 ppm. Significantly increased incidences of non-neoplastic lesions primarily were observed in the nasal cavity (squamous metaplasia and epithelial hyperplasia), larynx (squamous metaplasia and inflammation), and trachea (squamous metaplasia and inflammation) of male and female rats exposed at 5 ppm; however, squamous metaplasia of the nasal cavity was not significantly increased in the females. Lymph node hyperplasia was significantly increased in females exposed at 5 ppm, and hepatic focal cell hyperplasia was significantly increased in females exposed at 1 and 5 ppm. Statistically significant changes in tumor incidence included increases in nasal adenomatous polyps in females exposed at 5 ppm and in males exposed at 1 and 5 ppm; increases in nasal villous polyps in males exposed at 5 ppm; and increases in thyroid carcinomas in males exposed at 5 ppm. The nasal tumors were associated with chronic local irritation, and most of the rat nasal tumors were seen at 12 months post-exposure. The first appearance of nasal tumors in male and female rats occurred at 20 and 23 months, respectively, following initiation of exposure.

Groups of 400 female C57BL/6 mice were exposed to hydrazine at 0.05, 0.25, or 1.0 ppm and maintained for 15 months post-exposure. No non-neoplastic pathology could be detected after hydrazine exposure. An increase in pulmonary adenomas observed in mice exposed at the highest concentration was marginal compared with concurrent controls. When those results were compared with data from an additional control group of 385 female C57BL/6 mice, there were no significant differences. Vernot et al. (1985) noted that the historical control incidence of pulmonary adenomas in C57BL/6 mice was 2-3% and considered the 3.2% increase observed at 1.0 ppm to be consistent with the background rate in that strain. Higher concentrations could not be assessed due to the high mortality indicated in previous studies (Haun and Kinkead 1973; MacEwen et al. 1974).

Groups of 200 hamsters exposed to hydrazine at 0.25, 1.0, or 5.0 ppm experienced increased mortality during the early phase of the study. All groups exhibited decreased body weights compared with controls; however, only animals exposed at 5 ppm showed significantly decreased body weights in the final months of the study. Hepatic, renal, and adrenal amyloidosis were increased significantly in all exposed groups, but 22-23% of the concurrent controls exhibited the same conditions. Amyloidosis was also significantly increased in the spleens of animals exposed at 1 and 5 ppm and in the thyroids of animals exposed at 0.

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