NEUROTOXICITY AND PATTERN OF ACETYLCHOLINESTERASE INHIBITION IN THE BRAIN-REGIONS OF RAT BY BROMOPHOS AND ETHYLBROMOPHOS

Bromophos (Bp) and ethylbromophos (EBp) are two structurally homologou s organophosphorus (OP) insecticides which show wide differences in th eir 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 tre mors and lacrimation, In vivo cholinesterase inhibition was in the ord er plasma > erythrocytes > brain, Experiments with equitoxic and equim olar doses showed that EBp is a more potent anticholinesterase compoun d than Bp, Since IC50 values for the brain AChE were similar for both OPs, the target enzyme sensitivity was not a major factor in their dif ferential toxicity, In vitro reactivation of serum ChE was significant ly higher in the case of EBp than that of Bp, AChE in the brain region s showed differential inhibition in vivo, The brain stem AChE inhibiti on was least by Bp, whereas it was highest in the case of EBp, Both th e OPs produced high AChE inhibition in the hippocampus, Differential i nhibition of AChE in the brain regions and its consequent effects may be important factors in the differential neurotoxicity of OPs. (C) 199 6 Society of Toxicology