Exploratory Approach of Developing Biomarkers for Linking Sub-Lethal Neonicotinoids Exposure and Health Risks

Abstract

Since the development of neonicotinoids, their usage has been growing dramatically in pest control while limited studies focused on their impact on human exposure. With a concern of the systemic property of neonicotinoids and their cumulative high frequency of usage, this dissertation thesis aimed to focus on the following three aspects: (1) human exposure assessment, (2) a novel biomarker, and (3) the associated metabolic pathways of cumulative neonicotinoids exposure at sub-lethal levels. In Chapter 1, we estimated the average daily intake distributions of neonicotinoids residues in fruit and vegetable consumptions in the U.S. population using residues data from the US Congress Cafeteria study and USDA Pesticide Data Program, and consumption data from the NHANES surveys. We integrated residues of six neonicotinoids into imidacloprid-equivalent exposure (IMIRPF) based on their relative toxicity compared to imidacloprid. We found the average daily intake distributions were generally below the regulatory standard, chronic reference dose (cRfD) while we discussed on limitations regarding the comprehensive inclusion of dietary exposure categories, the precision of analytical methods used, and the potential revision of the stringency of current regulatory levels based on novel biomarkers. In Chapter 2, we identified increasing relative mitochondrial DNA copy number (RmtDNAcn) as a potential biomarker to reflect sub-lethal neonicotinoids exposure in a honeybee model. Even without large enough samples to declare statistically significant associations, we found higher levels of RmtDNAcn in later-brood generations within a colony and in bees fed with neonicotinoids. Additionally, we found that neonicotinoids exposure and increasing RmtDNAcn were related to faster onset of bee disappearance and occurrence of hives’ mortality over the winter. In Chapter 3, we explored energy metabolism related pathways that could help explain the influence of cumulative sub-lethal neonicotinoids treatments and increasing RmtDNAcn levels in honeybees. Overall, we detected statistically significant abundance changes in metabolites due to biological aging that are aligned with findings of previous literature. We also found perturbation of metabolites in the TCA cycle and glutathione metabolisms associated with neonicotinoids treatments and change in RmtDNAcn levels. Future biological research on neonicotinoids should focus on these metabolites to validate our findings.