COMPARATIVE INHIBITION OF RODENT AND HUMAN ERYTHROCYTE ACETYLCHOLINESTERASE BY CARBOFURAN AND CARBARYL

Acetylcholinesterase (AChE) inhibition is a common measure of carbamat e toxicity. Since most studies predict AChE inhibition in humans using the rat as an animal model, this study evaluated the comparative inhi bition of rodent and human erythrocyte AChE by two commonly used antic holinesterase carbamates. Comparative hematology, K-m and V-max IC50 a nd K-i were established for erythrocyte AChE from male Sprague-Dawley rats (200-250 g) and healthy human volunteers (1944 years old). Erythr ocyte AChE activity was measured using a modified radiometric method. No significant species differences were present in hematology. Rodent AChE K-m (0.69 +/- 0.15 mM) and V-max (0.53 +/- 0.13 nmol/min/mg prote in) were lower than human K-m (1.87 +/- 0.26 mM) and V-max (2.92 +/- 0 .27 nmol/min/mg protein). Carbofuran IC50 values for rodent (0.04 +/- 0.01 mu M) were similar to human IC50 (0.025 +/- 0.005 mu M); however, the carbaryl IC50 for rodent AChE (4.84 +/- 0.42 mu M) was higher tha n that for human AChE (1.23 +/- 0.108 mu M). No significant species di fferences were evident in K-i for carbofuran (rodent K-i of 18.35 +/- 1.96 nM and human K-i of 16.81 +/- 1.75 nM) or carbaryl (rodent K-i of 2.63 +/- 0.36 mu M and human K-i of 3.03 +/- 0.53 mu M). These data s uggest that, despite inherent differences in kinetics of substrate hyd rolysis between rodent and human erythrocyte AChE, the kinetics of inh ibition in vitro by carbofuran and carbaryl as estimated by the compar ative bimolecular rate constants (K-i) are quite similar between speci es and may be useful in human risk assessment. (C) 1994 Academic Press , Inc.