Health Risk Assessment of Women in Submarines (Phase III): Two Generation Developmental and Reproductive Safety Evaluation of Major Submarine Atmosphere Components (CO, CO2, and O2) in Rats (Rattus norvegicus).

摘要

This study evaluated general, reproductive and developmental effects on male and female rats exposed to mixed atmospheres of three critical submarine air components (CO, CO2, and O2) at concentrations approximating the existing submarine standards for continuous exposure limits (CELs) and emergency exposure limits (24-hour EEL and 1-hour EEL). This report describes a 90-day, two-generation evaluation of the general health and reproductive effects in male and female rats exposed to atmospheres representing the Navy's current limits. This study also evaluated the development and reproductive ability of first generation offspring exposed in utero to gestation day (GD) 19, and the development of the unexposed second generation offspring. Male and Female rats were exposed via whole body inhalation to clean air, a low-dose gas mixture, a mid-dose gas mixture and a high-dose gas mixture for 23 hours per day for 70 days, followed by a 14-day mating period that was also under exposure. Impregnated dams continued exposure to GD 19. Male and female rats were exposed for 90 to105 days. No adverse reproductive effects were identified in either the exposed parents or first generation offspring during mating, gestation or parturition. There were no adverse changes to the estrous cycle, or in reproductive hormone concentrations, due to the exposures. The only exposure-related effects were reduced weight gains of marginal biological significance and a normal adaptive up-regulation of erythropoiesis, both effects being most notable in male rats from the high-dose group. There were no adverse, dose-related health effects identified in either the exposed parents or offspring based on clinical data (hematology; serum chemistry) or on physiological data (gross pathology; histopathology; organ weights). Additionally, neurobehavioral tests of emotionality, exploratory behavior, motor activity, and cognitive functions (learning and memory) identified no apparent developmental deficits.