Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo, Chiba 260-8675, Japan.
Department of Legal Medicine, Graduate School of Medicine, Chiba University, Chuo, Chiba 260-8675, Japan.
Chem Res Toxicol. 2021 Jan 18;34(1):161-168. doi: 10.1021/acs.chemrestox.0c00472. Epub 2021 Jan 6.
Methomyl, (,)-methyl -{[(methylamino)carbonyl]oxy}ethanimidothioate, is a widely used pesticide that has been detected in many fatal cases of accidental exposure or suicide. Forensic toxicologists have been baffled that the blood methomyl concentration in persons who have died of methomyl poisoning is much lower than the expected concentration in blood. In this study, we speculated two mechanisms underlying the insufficient recovery of methomyl in blood. First, methomyl is decomposed by serum albumin as esterase. Second, methomyl is bound to a specific blood protein, resulting in insufficient recovery in the free form. However, human serum albumin does not show esterase activity for the decomposition of methomyl. On the contrary, specific methomyl hemoglobin adducts have been detected by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra indicated that methomyl was specifically bound to tryptophan (W), tyrosine (Y), and valine (V) residues in hemoglobin. The amounts of W- and V-adducts dose-dependently increased when the methomyl concentration was lower than the lethal concentration. In addition, the W-adduct was detected in blood sampled from an autopsied subject who died of intentional methomyl ingestion, suggesting that the W-adduct could be used as a biomarker of methomyl poisoning. We were able to estimate the amount of methomyl ingested on the basis of the amount of the W-adduct.
灭多威，（S）-甲基-{[(甲氨基）羰基]氧}乙亚氨酸硫代甲酯，是一种广泛使用的杀虫剂，在许多意外暴露或自杀导致的致命病例中都有被检测到。法医学毒理学家感到困惑的是，死于灭多威中毒的人血液中的灭多威浓度远低于血液中的预期浓度。在这项研究中，我们推测了血液中灭多威回收不足的两个机制。首先，灭多威作为酯酶被血清白蛋白分解。其次，灭多威与一种特定的血液蛋白结合，导致游离形式的回收不足。然而，人血清白蛋白对灭多威的分解没有酯酶活性。相反，通过液相色谱四极杆飞行时间质谱（LC-Q/TOF-MS）已经检测到了特定的灭多威血红蛋白加合物。质谱表明，灭多威特异性地结合到血红蛋白中的色氨酸（W）、酪氨酸（Y）和缬氨酸（V）残基上。当灭多威浓度低于致死浓度时，W-和 V-加合物的量呈剂量依赖性增加。此外，在死于故意摄入灭多威的尸检对象的血液中检测到 W-加合物，表明 W-加合物可作为灭多威中毒的生物标志物。我们能够根据 W-加合物的量来估计摄入的灭多威的量。
