Effects of dose-rate on chronic toxicity of ethylene oxide: preliminary report.
Moorman-WJ; Clark-JC; Shaw-PB; Ong-T; Schrader-SM; Lynch-DW; Lewis-TR
Toxicologist 1992 Feb; 12(1):354
Male F344 rats were exposed to ethylene oxide (ETO) in four treatment groups (200 each) as follows: 100 ppm for 6 hrs [Low Dose-Rate (D/R)]; 300 ppm for 2 hrs (Medium D/R); 600 ppm for 1 hr (High D/R); and clean air controls. Exposures were on a 5 day/week schedule for up to 24 months. Each ETO treatment received an equal product of concentration X time (600 ppm-hrs). Early sacrifices (3, 6, & 9 months) involved evaluation of spermatotoxic, cytogenetic, and immunotoxic indices and DNA adduction. Surviving rats were sacrificed following 24 months of exposure. DNA adduct, immunotoxic, and histopathologic evaluations are in progress. All ETO treatments demonstrated increased mortality, however mortality was not related to dose-rate. The Low D/R and Medium D /R groups had lower mean body weights than the High D/R or the controls. Spleen weights were higher and brain weights were lower in the Low D/R and Medium D/R treatments. All ETO exposed rats demonstrated reduced testicular weights, and the Low D/R and Medium D/R groups had lower sperm counts than the High D/R or controls. The Low D/R also had lower sperm velocity (curvilinear) than the controls. The cytogenetic studies revealed that genetic damage occurred more readily in spleen cells than in bone marrow cells. All ETO treatments demonstrated a higher frequency of sister chromatid exchanges (SCE) in spleen cells compared to the controls after 3 months of exposure. At 3 and 6 months of exposure, an increased SCE frequency was found in bone marrow cells in the Low D/R group. The impact of dose-rate varies in different tissues and may relate to rates of perfusion, repair, and cell proliferation.
Laboratory-animals; Animals; Animal-studies; Exposure-levels; Dose-response; Toxic-effects; Reproductive-effects; Immunotoxins; Cytotoxins; Genetics
The Toxicologist. Society of Toxicology 31st Annual Meeting, February 23-27,1992, Seattle, Washingtion