Human metabolism and urinary excretion of seven neonicotinoids and neonicotinoid-like compounds after controlled oral dosages

• DOI: 10.1007/s00204-021-03159-0
• Publication Date: 2021-10-13T12:56:19Z
• Authors: Sonja A. Wrobel; Daniel Bury; Heiko Hayen; Holger M. Koch; Thomas Brüning; Heiko U. Käfferlein
• Keywords: Neonicotinoid; Thiacloprid; Clothianidin; Acetamiprid

Few human data on exposure and toxicity are available neonicotinoids neonicotinoid-like compounds (NNIs), an important group of insecticides worldwide. Specifically, assessment humans by biomonitoring remains a challenge due to the lack appropriate biomarkers. We investigated metabolism metabolite excretion in urine acetamiprid (ACE), clothianidin (CLO), flupyradifurone (FLUP), imidacloprid (IMI), sulfoxaflor (SULF), thiacloprid (THIAC) thiamethoxam (THIAM) after single oral dosages at currently acceptable daily intake levels European Food Safety Authority. Consecutive post-dose samples were collected up 48 h. Suspect screening tentative metabolites was carried out liquid chromatography-high-resolution mass spectrometry. Screening hits identified based their accurate mass, isotope signal masses ratios, product ion spectra, kinetics. found, with exception SULF, extensive metabolization NNIs specific which excreted next parent compounds. Overall, 24 detected intensities indicative high metabolic relevance. Phase-I predominantly derived mono-oxidation (such as hydroxy-FLUP, -IMI, -THIAC) oxidative N-desalkylation N-desdifluoroethyl-FLUP N-desmethyl-ACE, -CLO -THIAM). IMI-olefin, obtained dehydration hydroxylated IMI, major IMI. SULF unchanged urine. Previously reported such 6-chloronicotinic acid or 2-chlorothiazole-4-carboxylic glycine derivatives either low not all seem less relevant for biomonitoring. Our highly controlled approach provides insight into suggests suitable biomarkers future environmentally exposures.