We investigated the inhibitory effects of 13 organophosphate esters (OPEs) and hydrolytic metabolites on the carboxylesterase activity of rat liver microsomes in vitro in order to examine whether there might be a potential impact on human health, and to elucidate the structure activity relationship. Among the test compounds, 2-ethylhexyl diphenyl phosphate (EDPhP) was the most potent inhibitor of carboxylesterase activity, as measured in terms of 4-nitrophenol acetate hydrolase activity, followed by tri-m-cresyl phosphate (TmCP), cresyl diphenyl phosphate (CDPhP) and triphenyl phosphate (TPhP). The IC₅₀ values were as follows: EDPhP (IC₅₀: 0.03 μM) > TmCP (0.4 μM) > CDPhP (0.8 μM) > TPhP (14 μM) > tris(1,3-dichloro-2-propyl) phosphate (17 μM) > tris(2-ethylhexyl) phosphate (77 μM) > tri-n-propyl phosphate (84 μM) > tris(2-chloroethyl) phosphate (104 μM) > tris(2-butoxyethyl) phosphate (124 μM) > tri-n-butyl phosphate (230 μM). The IC₅₀ value of EDPhP was three orders of magnitude lower than that of bis(4-nitrophenyl) phosphate, which is widely used as an inhibitor of carboxylesterase. Trimethyl phosphate, triethyl phosphate and tris(2-chloroisopropyl) phosphate slightly inhibited the carboxylesterase activity; their IC₅₀ values were above 300 μM. Lineweaver-Burk plots indicated that the inhibition by several OPEs was non-competitive. Diphenyl and monophenyl phosphates, which are metabolites of TPhP, showed weaker inhibitory effects than that of TPhP.

我们研究了13种有机磷酸酯（OPEs）和水解代谢物对大鼠肝微粒体羧基酯酶活性的体外抑制作用，以检查是否可能对人体健康产生潜在影响，并阐明其结构活性关系。间的试验化合物，2-乙基己基二苯基磷酸酯（EDPhP）是羧酸酯酶活性的最有效的抑制剂，如在4-硝基苯酚乙酸酯水解酶活性的衡量，由三-随后米-cresyl磷酸盐（TMCP），甲苯基二苯基磷酸酯（ CDPhP）和磷酸三苯酯（TPhP）。IC ₅₀值如下：EDPhP（IC ₅₀：0.03μM）> TmCP（0.4μM）> CDPhP（0.8μM）> TPhP（14μM）>磷酸三（1,3-二氯-2-丙基）酯（17μM）>磷酸三（2-乙基己基）酯（77 μM）>三ñ丙基磷酸盐（84μM）>三（2-氯乙基）磷酸酯（104μM）>三（2-丁氧基乙基）酯（124μM）>三ñ丁基磷酸盐（230μM）。EDP​​hP的IC ₅₀值比被广泛用作羧酸酯酶抑制剂的双（4-硝基苯基）磷酸酯低3个数量级。磷酸三甲酯，磷酸三乙酯和磷酸三（2-氯异丙基）酯略微抑制羧酸酯酶的活性。他们的IC ₅₀值高于300μM。Lineweaver-Burk图表明，几种OPE的抑制作用是非竞争性的。磷酸二苯酯和磷酸单苯酯是TPhP的代谢产物，其抑制作用比TPhP弱。