Misik Jan, Pavlikova Ruzena, Cabal Jiri, Kuca Kamil
Faculty of Military Health Sciences, University of Defence , Trebesska, Hradec Kralove , Czech Republic and.
Drug Chem Toxicol. 2015 Jan;38(1):32-6. doi: 10.3109/01480545.2014.900070. Epub 2014 Mar 18.
Highly toxic organophosphorus compounds (V- and G-nerve agents) were originally synthesized for warfare or as agricultural pesticides. Data on their acute toxicity are rare and patchy. Therefore, there is a need for integrated summary comparing acute toxicity of organophosphates using different administration routes in the same animal model with the same methodology. Based on original data, a summary of in vivo acute toxicity of selected V- and G-nerve agents (tabun, sarin, soman, VX, Russian VX) and organophosphates paraoxon (POX) and diisopropyl fluorophosphate (DFP) in rats has been investigated.
Male Wistar rats were exposed to organophosphates in several administration routes (i.m., i.p., p.o, s.c., p.c.). The acute toxicity was evaluated by the assessment of median lethal dose (LD50, mg kg(-1)) 2, 4, and 24 hours post exposure.
V-agents were the most toxic presented with LD50 ranged from 0.0082 mg kg(-1) (VX, i.m.) to 1.402 mg kg(-1) (Russian VX, p.o.), followed by G-agents (LD50 = 0.069 mg kg(-1)/soman, i.m./ - 117.9 mg kg(-1)/sarin, p.c./), organophosphate POX and DFP (LD50 = 0.321 mg kg(-1)/POX, i.m./ - 420 mg kg(-1)/DFP, p.c./). Generally, i.m. administration was the most toxic throughout all tested agents and ways of administration (LD50 = 0.0082 mg kg(-1)/VX/ - 1.399 mg kg(-1)/DFP/) whereas p.c. way was responsible for lowest acute toxicity (LD50 = 0.085 mg kg(-1)/VX/ - 420 mg kg(-1)/DFP/).
The acute toxicity of selected organophosphorus compounds is summarized throughout this study. Although the data assessed in rats are rather illustrative prediction for human, it presents a valuable contribution, indicating the toxic potential and harmfulness of organophosphates.
高毒性有机磷化合物(V型和G型神经毒剂)最初是为战争用途或作为农业杀虫剂而合成的。关于它们急性毒性的数据稀少且不完整。因此,有必要进行综合总结,以便在同一动物模型中使用相同方法比较不同给药途径的有机磷化合物的急性毒性。基于原始数据,对选定的V型和G型神经毒剂(塔崩、沙林、梭曼、VX、俄罗斯VX)以及有机磷酸酯对氧磷(POX)和二异丙基氟磷酸酯(DFP)在大鼠体内的急性毒性进行了总结研究。
雄性Wistar大鼠通过多种给药途径(肌肉注射、腹腔注射、口服、皮下注射、经皮)接触有机磷化合物。通过评估接触后2小时、4小时和24小时的半数致死剂量(LD50,mg kg⁻¹)来评价急性毒性。
V型神经毒剂毒性最强,LD50范围为0.0082 mg kg⁻¹(VX,肌肉注射)至1.402 mg kg⁻¹(俄罗斯VX,口服),其次是G型神经毒剂(LD50 = 0.069 mg kg⁻¹/梭曼,肌肉注射/ - 117.9 mg kg⁻¹/沙林,经皮/)、有机磷酸酯POX和DFP(LD50 = 0.321 mg kg⁻¹/POX,肌肉注射/ - 420 mg kg⁻¹/DFP,经皮/)。一般来说,在所有受试药剂和给药方式中,肌肉注射给药毒性最大(LD50 = 0.00 82 mg kg⁻¹/VX/ - 1.399 mg kg⁻¹/DFP/),而经皮给药急性毒性最低(LD50 = 0.085 mg kg⁻¹/VX/ - 420 mg kg⁻¹/DFP/)。
本研究总结了选定有机磷化合物的急性毒性。尽管在大鼠身上评估的数据对人类而言只是具有一定说明性的预测,但它提供了有价值的参考,表明了有机磷化合物的潜在毒性和危害性。