Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures

Abstract

The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO₂; levels elevated above ambient), and oxygen (O₂; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO₂ and 20.6% O₂), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO₂ and 15.0% O₂), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

• Carbon dioxide
• carbon monoxide
• hematology
• hypoxia
• inhalation
• mixtures
• neurobehavioral
• reproductive toxicity

Acknowledgements

This work was approved by the WPAFB Institutional Animal Care and Use Committee (Protocol F-WA-2010-0116-A). 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 US Government. This article is approved for public release, and distribution unlimited. The authors wish to thank the scientific and technical staffs at Navy Medical Research Unit Dayton (NAMR-D). 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 Okolica, Jessica Sharits and the vivarium staff of the US Air Force 711th Human Performance Wing provided the daily efforts necessary for animal husbandry and analytical observations. Mary Eaton and Molly Miklasevich conducted the neurobehavioral testing. Andrew Osterburg provided critical data analysis. LtCol Deidre E. Stoffregen, US Army, 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. This effort was supported by the Office of Naval Research under Work Unit Number 61064. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the US Government. The authors are military service members, employees 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 the 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.