Thiodicarb and Methomyl Tissue Distribution in a Fatal Multiple Compounds Poisoning

Abstract

Thiodicarb is a nonsystemic carbamate insecticide whose acetylcholinesterase activity is related to its main methomyl degradation product. A 40-year-old woman was found dead in her car. Empty packages of medicines and an open bottle of Larvin containing thiodicarb were found near her body. No signs of violence nor traumatic injuries were noticed upon autopsy, and police investigations strongly suggested a suicide. Systematic toxicological analysis performed on postmortem specimens revealed the presence of various sedatives, hypnotics, and antipsychotic drugs in blood, urine, and gastric content. Some of the compounds identified were determined at blood concentrations well above the known therapeutic concentrations: zolpidem (2.87 mg/L), bromazepam (2.39 mg/L), nordazepam (4.21 mg/L), and levopremazine (0.64 mg/L). Specific analysis of thiodicarb and of its methomyl metabolite was then performed on all fluids and tissues collected during autopsy by liquid chromatography ion trap tandem mass spectrometry (LC-MS-MS). The anticholinesterase capacity of blood, urine, and gastric content collected at autopsy was 83%, 82%, and 32%, respectively (normal value: 0%). The presence of thiodicarb in the bottle found near the body corroborates the hypothesis of an intake of that compound. Although thiodicarb was only detected in gastric content (24.3 mg/L), its methomyl metabolite was quantified in most postmortem tissues and fluids: gastric content (19.9 mg/L), peripheral blood (0.7 mg/L), urine (8.5 mg/L), bile (2.7 mg/L), liver (0.7 mg/kg), kidney (1.7 mg/kg), lung (1.5 mg/kg), brain (9.3 mg/kg), and heart (3.6 mg/kg).

Ethaninidothioic acid (R5421) is not a selective inhibitor of platelet phospholipid scramblase activity

“…Thiodicarb is a synthetic carbamate pesticide that is extensively used for crop protection. It has been shown to have some toxicity including systemic organ damage, including occasional signs of haemorrhage and inhibition of AChE activity (Dias et al, 2013; Hoizey et al, 2008). No effects on platelets have been previously described.…”

Current Approaches to and Future Perspectives on Methomyl Degradation in Contaminated Soil/Water Environments

“…Methomyl has been detected in the stomach, peripheral blood, brain, and heart of factory workers and farmers who are frequently exposed to high concentrations of methomyl. Higher concentrations of methomyl can cause death [20]. An agricultural worker reportedly died after inhaling a heavy dose of methomyl while flying a pesticide-spraying aircraft [19].…”

“…According to a survey conducted in France, 4.2% of the population was directly or indirectly poisoned with methomyl during the period 2012-2016 [18]. It has been detected in the blood, liver, kidneys, and brain of humans and animals [19][20][21]. Methomyl has been banned in many European countries due to its extremely high residual toxicity towards mammals, birds, and the environment [18].…”

Simultaneous determination of thiodicarb and its main metabolite residues in cotton by ultra-performance liquid chromatography coupled to tandem mass spectrometry

“…The inactivation of cholinesterase produces symptoms of intoxication that include excessive salivation, sweating, blurred vision, nausea, vomiting, seizures, and even death due to paralysis of the respiratory muscles. 2 Cultivated cotton is an important natural bre crop and is grown commercially in many countries of the world. Cottonseed is an important secondary product of the cotton industry and its main derivatives are the cottonseed cake and cottonseed meal which are used for making animal feed, and the cottonseed oil which is used for both household and industrial food preparation.…”