Citation

Yamagishi Y, Nagasawa S, Iwase H, Ogra Y. J. Toxicol. Sci. 2022; 47(4): 139-146.

Copyright

(Copyright © 2022, Doku Sayo Kenkyukai)

DOI

10.2131/jts.47.139

PMID

35370241

Abstract

Methidathion [3-(dimethoxyphosphinothioylsulfanylmethyl)-5-methoxy-1,3,4-thiadiazol-2-one; hereinafter DMTP], one of the most widely used organophosphorus pesticides, has been detected in some clinical cases of accidental exposure and suicide in Japan. It has been reported that DMTP concentration is decreased in blood. In this study, it is difficult to recover DMTP in the free form because DMTP is bound to human serum albumin (HSA). We detected DMTP adducts in HSA by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that DMTP was preferably bound to the lysine (K), tyrosine (Y), and cysteinylproline (CP) residues of HSA. The concentrations of K-adduct, DMTP-Y-adduct and DMTP-CP-adduct were increased in vitro in a dose-dependent fashion when DMTP concentration was lower than the lethal dose. Furthermore, the DMTP-Y-adduct and DMTP-CP-adduct were also detected in post-mortem blood of an autopsied subject who died by intentional DMTP ingestion. The results suggested that the DMTP-Y-adduct and DMTP-CP-adduct could be used as a biomarker of DMTP poisoning, and the decrease concentration of DMTP in blood after death could be determined on the basis of the concentration of the DMTP-CP-adduct in blood.

Language: en

Keywords

Humans; Pesticides; Organophosphorus Compounds; Cysteinylproline adduct; Human serum albumin; Methidathion; Organothiophosphorus Compounds; Post-mortem change; Serum Albumin, Human; Tyrosine adduct