Female rats are less susceptible during puberty to the lethal effects of percutaneous exposure to VX

Abstract

Nerve agents with low volatility such as VX are primarily absorbed through the skin when released during combat or a terrorist attack. The barrier function of the stratum corneum may be compromised during certain stages of development, allowing VX to more easily penetrate through the skin. However, age-related differences in the lethal potency of VX have yet to be evaluated using the percutaneous (pc) route of exposure. Thus, we estimated the 24 and 48 h median lethal dose for pc exposure to VX in male and female rats during puberty and early adulthood. Pubescent, female rats were less susceptible than both their male and adult counterparts to the lethal effects associated with pc exposure to VX possibly because of hormonal changes during that stage of development. This study emphasizes the need to control for both age and sex when evaluating the toxicological effects associated with nerve agent exposure in the rat model.

Delayed midazolam dose effects against soman in male and female plasma carboxylesterase knockout mice

“…38 Female adult rats may be more susceptible to the lethal effects of intramuscular sarin exposure 39 or whole-body exposure to sarin or cyclosarin; 22,23,25 however, our laboratory observed no sex difference in SC sarin exposure in rats. 23 Interestingly, while female rats are reported to be more sensitive to the lethal effects of GD and sarin, [22][23][24][25][26] in multiple mouse strains, female mice are less sensitive to the lethal effects of sarin. 40 In the present study, female mice in estrus were less sensitive to the lethal effects of GD toxicity compared with male mice, as well as compared with female mice in proestrus.…”

“…A few studies report female rats to be more sensitive to the lethal effects of GD or sarin compared with male rats. [22][23][24][25][26] The aforementioned studies, how-ever, were conducted without taking into consideration the estrous cycle stage at the moment of CWNA exposure, which may impact response to toxic exposure. In rats, the lethal effects of subcutaneous (SC) exposure to sarin vary depending on the stage of the estrous cycle, with female rats having lower susceptibility during proestrus.…”

“…However, the effects of sex are only sporadically reported in the literature and are, at times, contradictory, as age, route of exposure, species, or stage of estrous may impact the outcome. A few studies report female rats to be more sensitive to the lethal effects of GD or sarin compared with male rats 22–26 . The aforementioned studies, however, were conducted without taking into consideration the estrous cycle stage at the moment of CWNA exposure, which may impact response to toxic exposure.…”