PMID- 14713564 OWN - NLM STAT- MEDLINE DCOM- 20040224 LR - 20191108 IS - 1528-7394 (Print) IS - 0098-4108 (Linking) VI - 67 IP - 4 DP - 2004 Feb 27 TI - Neurological deficits induced by malathion, DEET, and permethrin, alone or in combination in adult rats. PG - 331-56 AB - 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. FAU - Abdel-Rahman, Ali AU - Abdel-Rahman A AD - Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. FAU - Dechkovskaia, Anjelika M AU - Dechkovskaia AM FAU - Goldstein, Larry B AU - Goldstein LB FAU - Bullman, Sara H AU - Bullman SH FAU - Khan, Wasiuddin AU - Khan W FAU - El-Masry, Eman M AU - El-Masry EM FAU - Abou-Donia, Mohamed B AU - Abou-Donia MB LA - eng PT - Journal Article PT - Review PL - England TA - J Toxicol Environ Health A JT - Journal of toxicology and environmental health. Part A JID - 100960995 RN - 0 (Drug Combinations) RN - 0 (Insecticides) RN - 134-62-3 (DEET) RN - 509F88P9SZ (Permethrin) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - EC 3.1.1.8 (Butyrylcholinesterase) RN - U5N7SU872W (Malathion) SB - IM MH - Acetylcholinesterase/metabolism MH - Administration, Topical MH - Animals MH - Behavior, Animal/drug effects MH - Brain/*drug effects/enzymology MH - Butyrylcholinesterase/metabolism MH - DEET/*toxicity MH - Drug Combinations MH - Insecticides/*toxicity MH - Malathion/*toxicity MH - Male MH - Permethrin/*toxicity MH - Rats MH - Rats, Sprague-Dawley RF - 63 EDAT- 2004/01/10 05:00 MHDA- 2004/02/26 05:00 CRDT- 2004/01/10 05:00 PHST- 2004/01/10 05:00 [pubmed] PHST- 2004/02/26 05:00 [medline] PHST- 2004/01/10 05:00 [entrez] AID - X15X9A3HGDQ27WT9 [pii] AID - 10.1080/15287390490273569 [doi] PST - ppublish SO - J Toxicol Environ Health A. 2004 Feb 27;67(4):331-56. doi: 10.1080/15287390490273569.