Abdel-Rahman Ali, Dechkovskaia Anjelika M, Goldstein Larry B, Bullman Sara H, Khan Wasiuddin, El-Masry Eman M, Abou-Donia Mohamed B
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
J Toxicol Environ Health A. 2004 Feb 27;67(4):331-56. doi: 10.1080/15287390490273569.
Malathion (O,O-dimethyl-S-[1,2-carbethoxyethyl]phosphorodithionate), DEET (N,N-diethyl-m-toluamide), and permethrin [(+/-)-cis/trans-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane carboxylic acid (3-phenoxyphenyl) methyl ester] are commonly used pesticides. To determine the effects of the dermal application of these chemicals, alone or in combination, the sensorimotor behavior, central cholinergic system, and histopathological alterations were studied in adult male Sprague-Dawley rats following a daily dermal dose of 44.4 mg/kg malathion, 40 mg/kg DEET, and 0.13 mg/kg permethrin, alone and in combination for 30 d. Neurobehavioral evaluations of sensorimotor functions included beam-walking score, beam walk time, inclined plane, and grip response assessments. Twenty-four hours after the last treatment with each chemical alone or in combination all behavioral measures were impaired. The combination of DEET and permethrin, malathion and permethrin, or the three chemicals together resulted in greater impairments in inclined performance than permethrin alone. Only animals treated with a combination of DEET and malathion or with DEET and permethrin exhibited significant increases in plasma butyrlcholinesterase (BChE) activity. Treatment with DEET or permethrin alone, malathion and permethrin, or DEET and permethrin produced significant increases in cortical acetylcholinesterase (AChE) activity. Combinations of malathion and permethrin or of DEET and permethrin produced significant decreases in midbrain AChE activity. Animals treated with DEET alone exhibited a significant increase in cortical m2 muscarinic ACh receptor binding. Quantification of neuron density in the dentate gyrus, CA1 and CA3 subfields of the hippocampus, midbrain, brainstem, and cerebellum revealed significant reductions in the density of surviving neurons with various treatments. These results suggest that exposure to real-life doses of malathion, DEET, and permethrin, alone or in combination, produce no overt signs of neurotoxicity but induce significant neurobehavioral deficits and neuronal degeneration in brain.
马拉硫磷（O,O-二甲基-S-[1,2-乙氧羰基乙基]二硫代磷酸酯）、避蚊胺（N,N-二乙基间甲苯酰胺）和氯菊酯[（+/-）-顺式/反式-3-（2,2-二氯乙烯基）-2,2-二甲基环丙烷羧酸（3-苯氧基苯基）甲酯]是常用的杀虫剂。为了确定单独或联合经皮施用这些化学物质的影响，在成年雄性斯普拉格-道利大鼠中，每日经皮给予44.4mg/kg马拉硫磷、40mg/kg避蚊胺和0.13mg/kg氯菊酯，单独及联合给药30天，研究了其感觉运动行为、中枢胆碱能系统和组织病理学改变。感觉运动功能的神经行为学评估包括横梁行走评分、横梁行走时间、斜面和抓握反应评估。单独或联合使用每种化学物质进行最后一次处理24小时后，所有行为指标均受损。避蚊胺与氯菊酯联合、马拉硫磷与氯菊酯联合或三种化学物质一起使用，导致斜面表现的损伤比单独使用氯菊酯更严重。仅用避蚊胺和马拉硫磷联合或避蚊胺和氯菊酯联合处理的动物血浆丁酰胆碱酯酶（BChE）活性显著增加。单独用避蚊胺或氯菊酯处理、马拉硫磷与氯菊酯处理或避蚊胺与氯菊酯处理均使皮质乙酰胆碱酯酶（AChE）活性显著增加。马拉硫磷与氯菊酯联合或避蚊胺与氯菊酯联合使中脑AChE活性显著降低。单独用避蚊胺处理的动物皮质m2毒蕈碱型ACh受体结合显著增加。对海马齿状回、CA1和CA3亚区、中脑、脑干和小脑的神经元密度进行定量分析发现，不同处理组存活神经元的密度显著降低。这些结果表明，暴露于实际生活剂量的马拉硫磷、避蚊胺和氯菊酯，单独或联合使用，不会产生明显的神经毒性迹象，但会导致显著的神经行为缺陷和脑内神经元变性。
