Characteristics of toxicokinetics and metabolic transformation of flonicamid in rats

Flonicamid (FLO), as a novel pyridinecarboxamide insecticide, has attracted wide attention because of its detection in human-derived samples. To evaluate its potential health risk, it is essential to clarify the absorption, distribution, and excretion characteristics of FLO. However, the currently available data are far from sufficient. Moreover, the biotransformation of FLO might cause the generation of bioactive metabolites, which is worthy of high attention. In this study, toxicokinetics and metabolites of FLO were investigated in male Sprague-Dawley rats by a single oral exposure of 5 mg FLO/kg body weight. The results revealed that FLO was rapidly absorbed with the peak plasma concentrations (2.06 ± 0.97 μg/mL) at 2 h post-administration. The half-life of plasma FLO was 7.36 h. FLO was extensively detected in rat heart (2.87 ± 2.16 ng/g), muscle (2.81 ± 2.00 ng/g), and brain (2.53 ± 0.34 ng/g) at 48 h post-administration. Four known metabolites were identified. 4-trifluoromenthylnicotinamide (TFNA-AM) was the only metabolite detected in plasma with the maximum level (102.30 ± 11.12 ng/mL) at 12 h, and a major metabolite in organs and urine. Notably, the detection of FLO and the metabolites in rat brain and testicles may imply their potential neurotoxicity and reproductive toxicity risks. FLO and its metabolites were mostly excreted through urine and feces within 24 h post-administration. Other than acylamino hydrolysis, cyano hydrolysis, and cyano hydration, FLO could be directly transformed to TFNA-AM by decyanomethyl group. These findings help to understand the absorption, distribution, metabolism, and excretion characteristics of FLO and provide reference for its application management in agriculture and risk assessment.