title: Comparison of the lethal effects of chemical warfare nerve agents across multiple ages.
abstract: Children may be inherently more vulnerable than adults to the lethal effects associated with chemical warfare nerve agent (CWNA) exposure because of their closer proximity to the ground, smaller body mass, higher respiratory rate, increased skin permeability and immature metabolic systems. Unfortunately, there have only been a handful of studies on the effects of CWNA in pediatric animal models, and more research is needed to confirm this hypothesis. Using a stagewise, adaptive dose design, we estimated the 24h median lethal dose for subcutaneous exposure to seven CWNA in both male and female Sprague-Dawley rats at six different developmental times. Perinatal (postnatal day [PND] 7, 14 and 21) and adult (PND 70) rats were more susceptible than pubertal (PND 28 and 42) rats to the lethal effects associated with exposure to tabun, sarin, soman and cyclosarin. Age-related differences in susceptibility were not observed in rats exposed to VM, Russian VX or VX.
authors.affiliation: US Army Medical Research Institute of Chemical Defense (USAMRICD), 2900 Ricketts Point Rd., Aberdeen Proving Ground, MD 21010, USA.
authors.forename: Linnzi K M
authors.initials: LK
authors.lastname: Wright
authors.affiliation: US Army Medical Research Institute of Chemical Defense (USAMRICD), 2900 Ricketts Point Rd., Aberdeen Proving Ground, MD 21010, USA.
authors.forename: Robyn B
authors.initials: RB
authors.lastname: Lee
authors.affiliation: Edgewood Chemical Biological Center (ECBC), 5183 Blackhawk Rd., Aberdeen Proving Ground, MD 21010, USA.
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Vincelli
authors.affiliation: Edgewood Chemical Biological Center (ECBC), 5183 Blackhawk Rd., Aberdeen Proving Ground, MD 21010, USA.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Whalley
authors.affiliation: US Army Medical Research Institute of Chemical Defense (USAMRICD), 2900 Ricketts Point Rd., Aberdeen Proving Ground, MD 21010, USA. Electronic address: lucille.a.lange.civ@mail.mil.
authors.forename: Lucille A
authors.initials: LA
authors.lastname: Lumley
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D000067397:Nerve Agents / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002619:Chemical Warfare Agents; D000067397:Nerve Agents
keywords: Chemical warfare nerve agent; Development; Median lethal dose; Rat; Subcutaneous