Related Experiment Video
Updated: Nov 22, 2025
Study on the Metabolism of Six Systemic Insecticides in a Newly Established Cell Suspension Culture Derived from Tea Camellia Sinensis L. Leaves
Published on: June 15, 2019
Post-Mortem Changes of Methomyl in Blood with Hemoglobin
Yoshikazu Yamagishi1,2, Hirotaro Iwase2, Yasumitsu Ogra1,2
1Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo, Chiba 260-8675, Japan.
Abstract:
Methomyl, (E,Z)-methyl N-{[(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 in vitro 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.
Insights
Forensic toxicologists found low blood methomyl levels. This study reveals methomyl binds to hemoglobin, forming adducts that can serve as biomarkers for poisoning and estimating ingested doses.
Area of Science:
- Forensic Toxicology
- Analytical Chemistry
- Biochemistry
Background:
- Methomyl is a common pesticide implicated in fatal poisonings.
- Low blood methomyl concentrations in deceased individuals pose a challenge for forensic analysis.
- Previous hypotheses suggested methomyl decomposition or protein binding as causes for low recovery.
Purpose of the Study:
- To investigate the reasons for the insufficient recovery of methomyl in blood.
- To identify specific mechanisms of methomyl interaction with blood components.
- To explore potential biomarkers for methomyl poisoning.
Main Methods:
- Incubation of methomyl with human serum albumin to test for esterase activity.
- Detection and characterization of methomyl-protein adducts using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS).
- Quantification of methomyl adducts in vitro and in blood samples from an autopsy case.
Main Results:
- Human serum albumin did not exhibit esterase activity towards methomyl.
- Specific methomyl-hemoglobin adducts were identified, primarily involving tryptophan, tyrosine, and valine residues.
- The formation of tryptophan and valine adducts increased dose-dependently in vitro.
- The tryptophan adduct was detected in blood from a methomyl poisoning victim.
Conclusions:
- Methomyl does not decompose via serum albumin esterase activity.
- Methomyl specifically binds to hemoglobin, forming detectable adducts.
- The methomyl-tryptophan hemoglobin adduct is a potential biomarker for methomyl poisoning.
- Quantification of the tryptophan adduct allows for estimation of ingested methomyl dose.
