Submarine exposure guideline recommendations for carbon dioxide based on the prenatal developmental effects of exposure in rats

Birth Defects Res. 2019 Jan 1;111(1):26-33. doi: 10.1002/bdr2.1417. Epub 2018 Dec 3.


Background: To protect crewmember health, the U.S. Navy sets exposure limits for more than 200 components of submarine atmospheres. The addition of females to nuclear submarines required a reevaluation of these exposure limits, originally established for all-male crews. In the case of carbon dioxide (CO2 ), the only available data suitable for deriving an exposure limit were from a 2010 study sponsored by the British Royal Navy that reported a debatable interpretation casting doubt on whether current U.S. Navy exposure limits served to protect fetal developmental health.

Methods: About 120 time-mated female Sprague-Dawley rats (Crl: CD[SD]) were exposed to CO2 at levels of 1.5%, 2.0%, 2.5%, and 3.0% from gestation days 6 to 20. Dams were euthanized and fetuses were examined.

Results: Findings with implications for exposure limits for CO2 during pregnancy were an increased mean litter proportion of early resorptions and a lower mean litter proportion of viable fetuses in the 3.0% CO2 group.

Conclusion: The results yield a No Observed Adverse Effect Level (NOAEL) of 2.5% and a Lowest Observed Adverse Effect Level (LOAEL) of 3.0%. The results reasonably allow a point of departure of 2.5% CO2 for deriving an exposure recommendation. An interspecies uncertainty factor was applied to derive a recommended 90-day continuous exposure limit (CEL) of 0.8% for CO2 . As reproductive endpoints that are developmental in nature must be assumed to result from a single exposure at a critical point during gestation, it is further recommended that the 24-hr emergency exposure limit (EEL) also be 0.8%.

Keywords: carbon dioxide; exposure limits; inhalation; prenatal; submarine.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Carbon Dioxide / metabolism
  • Carbon Dioxide / toxicity*
  • Disease Models, Animal
  • Female
  • Fetal Development / drug effects
  • Fetus / drug effects
  • Military Personnel
  • No-Observed-Adverse-Effect Level
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Sprague-Dawley
  • Reproduction / drug effects
  • Submarine Medicine / methods
  • Submarine Medicine / standards*


  • Carbon Dioxide