Carbon monoxide (CO), carbon dioxide (CO2) and low-level oxygen (O2) (hypoxia) are submarine atmosphere components of highest concern because of a lack of toxicological data available to address the potential effects from long-duration, combined exposures on female reproductive and developmental health. In this study, subchronic toxicity of mixed atmospheres of these three submarine air components was evaluated in rats. Male and female rats were exposed via inhalation to clean air (0.4 ppm CO; 0.13% CO2; 20.6% O2) (control), a low-dose (5.0 ppm CO; 0.41% CO2; 17.1% O2), a mid-dose (13.9 ppm CO; 1.19 or 1.20% CO2; 16.1% O2) and a high-dose (89.9 ppm CO; 2.5% CO2; 15.0% O2) gas mixture for 23 h per day for 70 d premating and a 14-d mating period. Impregnated dams continued exposure to gestation day 19. Adverse reproductive effects were not identified in exposed parents (P0) or first (F1) and second generation (F2) offspring during mating, gestation or parturition. No adverse changes to the estrous cycle or in reproductive hormone concentrations were identified. The exposure-related effects were reduced weight gains and adaptive up-regulation of erythropoiesis in male rats from the high-dose group. No adverse, dose-related health effects on clinical data or physiological data were observed. Neurobehavioral tests identified no apparent developmental deficits at the tested levels of exposure. In summary, subchronic exposures to the submarine atmosphere gases did not affect the ability of the exposed rats or their offspring to reproduce and did not appear to have any significant adverse health effects.
Keywords: Carbon dioxide; carbon monoxide; developmental toxicity; inhalation; mixtures; neurobehavioral; reproductive toxicity; submarine atmosphere.