title: Toxicity of the combined nerve agents GB/GF in mice: efficacy of atropine and various oximes as antidotes.
abstract: The toxicity of a combination of isopropyl methylphosphonofluoridate (sarin; GB) and cyclohexyl methylphosphonofluoridate (GF) and the efficacy of various oxime reactivators in combination with atropine against the combined GB/GF challenge were evaluated in mice. The 24-h s.c. LD50 of the GB/GF combination was 1.15 mumol/kg (1.10-1.21; 95% confidence limits). Mice administered GB/GF displayed typical signs of nerve agent poisoning such as tremors and convulsions, with death most likely due to anoxia subsequent to respiratory arrest. The GB/GF LD50 value was comparable to the s.c. LD50 of 1.35 and 1.21 mumol/kg for GF and GB in mice, respectively. Combining the two nerve agents did not result in potentiation of the toxicity. In combination with atropine sulfate (17.4 mg/kg, i.p.), which alone did not reduce mortality, the oximes tested, 2-PAM, obidoxime and HI-6, were all effective when administered 5 min before 3 x LD50 dose of GB/GF with 24-h ED50 values of 102.5, 18.22 and 1.96 mumol/kg, respectively. Use of the GB/GF combination does not appear to confer any unique toxicity profile and appears to be easily treated with the standard therapy of a cholinolytic and oxime.
authors.affiliation: Biomedical Defence Section, Defence Research Establishment Suffield, Ralston, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Clement
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000506:poisoning / Q000633:toxicity*; D004357:Drug Synergism; D007279:Injections, Subcutaneous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D011041:Poisoning / Q000188:drug therapy; D012524:Sarin / Q000008:administration & dosage / Q000506:poisoning / Q000633:toxicity*
chemical_list: D000931:Antidotes; D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D010091:Oximes; D001285:Atropine; D012524:Sarin; C053914:cyclohexyl methylphosphonofluoridate