Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. II. Ninety-day study

Abstract

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.

• Carbon dioxide
• carbon monoxide
• developmental toxicity
• inhalation
• mixtures
• neurobehavioral
• reproductive toxicity
• submarine atmosphere

Acknowledgments

Michael Grimm, Jim Reboulet, Brian Sharits and Brian Wong were essential in the setup and conduct of inhalation exposures. Sue Prues was invaluable for her coordination and facilitation of protocol tasks as the Laboratory Manager. Tracy Doyle was indispensable in conducting the estrous cycle monitoring and measuring other biological endpoints. Angela Hulgan, David Lemmer, Michelle Goodwin, Jessica Sharits, Nathan Gargas and the vivarium staff of the U.S. Air Force 711 Human Performance Wing provided the daily efforts necessary for animal husbandry and analytical observations. Mary Eaton and Molly Miklasevich assisted in conducting neurobehavioral testing. Andrew Osterburg provided critical statistical data analysis. LtCol Deidre E. Stoffregen, US Army Veterinary Corps, provided vital capability with her exceptional pathology consultation. Karen Mumy and Pedro Ortiz assisted the Necropsy Team (as listed above) in collecting and preserving the animal tissue samples for analysis. And, a special thanks to Richard Erickson, whose resource coordination and sponsor interface were essential to the promotion and successful completion of the study.

Declaration of interest

There are no conflicts of interest to declare.

The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. Government.

The authors are military service members, employees of the US Government, or contract employees of the US Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a US Government work as a work prepared by a military service member or employee of the US Government as part of that person’s official duties.

This work was supported by Office of Naval Research (ONR) under Work Unit Number 61064. The study was approved by the Wright-Patterson Air Force Base Institutional Animal Care and Use Committee (Protocol F-WA-2010-0116-A) and conducted in compliance with the Animal Welfare Act and all applicable Federal regulations governing the protection of animals in research.

Supplementary materials online only – For review only at proofing stage.

Supplemental data related to this article can be found online at http://www.dtic.mil/dtic/tr/fulltext/u2/a553409.pdf