Comparative inhibition of rodent and human erythrocyte acetylcholinesterase by carbofuran and carbaryl.
1994
Rao P.S. | Roberts G.H. | Pope C.N. | Ferguson P.W.
Acetylcholinesterase (AChE) inhibition is a common measure of carbamate toxicity. Since most studies predict AChE inhibition in humans using the rat as an animal model, this study evaluated the comparative inhibition of rodent and human erythrocyte AChE by two commonly used anticholinesterase carbamates. Comparative hematology, Km and Vmax, IC50, and Ki were established for erythrocyte AChE from male Sprague-Dawley rats (200-250 g) and healthy human volunteers (19-44 years old). Erythrocyte AChE activity was measured using a modified radiometric method. No significant species differences were present in hematology. Rodent AChE Km (0.69 +/- 0.15 mM) and Vmax (0.53 +/- 0.13 nmol/min/mg protein) were lower than human Km (1.87 +/- 0.26 mM) and Vmax (2.92 +/- 0.27 nmol/min/mg protein). Carbofuran IC50 values for rodent (0.04 +/- 0.01 micromolar) were similar to human IC50 (0.025 +/- 0.005 micromolar); however, the carbaryl IC50 for rodent AChE (4.84 +/- 0.42 micromolar) was higher than that for human AChE (1.23 +/- 0.108 micromolar). No significant species differences were evident in Ki for carbofuran (rodent Ki of 18.35 +/- 1.96 nM and human Ki of 16.81 +/- 1.75 nM) or carbaryl (rodent Ki of 2.63 +/- 0.36 micromolar and human Ki of 3.03 +/- 0.53 micromolar). These data suggest that, despite inherent differences in kinetics of substrate hydrolysis between rodent and human erythrocyte AChE, the kinetics of inhibition in vitro by carbofuran and carbaryl as estimated by the comparative bimolecular rate constants (Ki) are quite similar between species and may be useful in human risk assessment.
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