Within-person variability of urinary neonicotinoids and their metabolites and recommendation for sampling strategy

Humans are exposed to neonicotinoid insecticides (NEOs) from various routes. Urine has been widely used to characterize the internal exposure levels of NEOs in humans. However, variable sampling methods can result in highly variable measurements of NEOs, potentially leading to misunderstanding of human exposure. In this study, we collected the first morning voids urine (FMVU), spot urine (SU), and 24 h urine (24hU) samples from 8 healthy adults during 7 consecutive days. The concentration, variability, and reproducibility of six parent NEOs (p-NEOs) and three NEOs metabolites (m-NEOs) were measured. Over 79 % of the urine samples had detectable levels of NEOs. Dinotefuran (DIN) and olefin-imidacloprid (of-IMI) were excreted in the highest concentration of p-NEO and m-NEO, respectively. All of the p-NEOs except thiacloprid (THD) and of-IMI were recommended as biomarkers for biomonitoring studies. The coefficient of variation (CV) and intraclass correlation coefficient (ICC) were used to evaluate the temporal variability and reproducibility of urinary NEOs in SU, FMVU and 24hU, respectively. We observed low ICCs ranging from 0.016 to 0.39 for NEOs regardless of the sample types. However, the higher CV and lower ICC values observed in SU samples suggested lower reproducibility compared to FMVU and 24hU samples. Significant correlations of several NEOs between FMVU and 24hU were also observed in the current study. Considering the comparable concentrations and similarity between FMVU and 24hU, our study proposed possible biomarkers and indicated that the potential for FMVU samples to estimate adequately an individual's exposure to NEOs. Therefore, we suggested FMVU as a sampling strategy in future human biomonitoring studies, while multiple samples were recommended to detect exposure over time intervals of weeks or months.