Younger rats are more susceptible to the lethal effects of sarin than adult rats: 24 h LC₅₀ for whole-body (10 and 60 min) exposures

Abstract

Chemical warfare nerve agents (CWNA) inhibit acetylcholinesterase and are among the most lethal chemicals known to man. Children are predicted to be vulnerable to CWNA exposure because of their smaller body masses, higher ventilation rates and immature central nervous systems. While a handful of studies on the effects of CWNA in younger animals have been published, exposure routes relevant to battlefield or terrorist situations (i.e. inhalation for sarin) were not used. Thus, we estimated the 24 h LC₅₀ for whole-body (10 and 60 min) exposure to sarin using a stagewise, adaptive dose design. Specifically, male and female Sprague-Dawley rats were exposed to a range of sarin concentrations (6.2–44.0 or 1.6–12.5 mg/m³) for either 10 or 60 min, respectively, at six different times during their development (postnatal day [PND] 7, 14, 21, 28, 42 and 70). For male and female rats, the lowest LC₅₀ values were observed for PND 14 and the highest LC₅₀ values for PND 28. Sex differences were observed only for PND 42 for the 10 min exposures and PND 21 and 70 for the 60 min exposures. Thus, younger rats (PND 14) were more susceptible than older rats (PND 70) to the lethal effects of whole-body exposure to sarin, while adolescent (PND 28) rats were the least susceptible and sex differences were minimal. These results underscore the importance of controlling for the age of the animal in research on the toxic effects associated with CWNA exposure.

Keywords:

• Chemical warfare nerve agent
• inhalation
• lethality
• development

Acknowledgements

The authors wish to thank Stephen Robertson, Andrew Bourne and Amanda Furman for their assistance with weighing the animals and preparing for exposures.

Declaration of interest

This research was supported by interagency agreement between the Biomedical Advanced Research and Development Authority (BARDA) and USAMRICD, as well as a memorandum of agreement between USAMRICD and ECBC. The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of Army, Department of Defense or the US Government.

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