Neurotoxicity and pattern of Acetylcholinesterase inhibition in the brain regions of rat by bromophos and ethylbromophos

Bromophos (Bp) and ethylbromophos (EBp) are two structur-ally homologous organophosphorus (OP) insecticides which show wide differences in their toxicity as well as neurotoxic symptoms in the laboratory rat. EBp is 24-fold more toxic (LD50 = 91 ± 14 mg/kg body wt) than Bp (LD50 = 2218 ± 195 mg/kg body wt) and only EBp produced characteristic tremors and lacrimation. In vivo cholinesterase inhibition was in the order plasma> eryth-rocytes> brain. Experiments with equitoxic and equimolar doses showed that EBp is a more potent anticholinesterase compound than Bp. Since ICSO values for the brain AChE were similar for both OPs, the target enzyme sensitivity was not a major factor in their differential toxicity. In vitro reactivation of serum ChE was significantly higher in the case of EBp than that of Bp. AChE in the brain regions showed differential inhibition in vivo. The brain stem AChE inhibition was least by Bp, whereas it was highest in the case of EBp. Both the OPs produced high AChE inhibition in the hippocampus. Differential inhibition of AChE in the brain regions and its consequent effects may be important factors in the differential neurotoxicity of OPs. © 1996 society of Toxicology Bromophos [0,0-dimethyl-0-(2,5-dichloro-4-bromophe-nyl) phosphorothioate] (Bp) and ethylbromophos [O, O-d\-ethyl-0-(2,5-dichloro-4-bromophenyl) phosphorothioate] (EBp) are nonsystemic insecticides effective against biting and sucking insect pests. Their use is recommended for infes-tation control of stored grain, ectoparasite control on domes-tic animals, and in public health (Eichler, 1972; Derache, 1977). Bp and EBp differ markedly with respect to their acute mammalian toxicity. The LD50 (oral) of Bp in rats is in the range of 1700-8000 mg/kg and that of EBp is 5 0