Developing a New Testing Paradigm for Risk-Assessment of Bee-Pesticide Interactions – Quantifying the Pace of Neonicotinoid Toxicokinetics

Abstract

Neonicotinoid pesticides, which are used to protect crops from certain pests, have been correlated with the decline of non-target insect species, including bumblebees. However, despite a myriad of studies into the interaction and impact of neonicotinoids, uncertainty remains as to the risks these xenobiotics pose to bees. In particular, the question of bioaccumulation, defined here as how long neonicotinoids persist in the body (i.e. fast or slow toxicokinetics) has not yet been determined for neonicotinoids and bumblebee species. Moreover, while the implications of bioaccumulation on non-target species are severe, regulatory standards continue to rely on acute paradigm testing (e.g. 48-hour LC50s or NOECs) that may inherently fail to capture bioaccumulation. First, I reviewed the literature on the pace of toxicokinetics for neonicotinoids, found in studies on enzymatic metabolism and receptor site bonding of these substances, which are the main pathways for clearance of xenobiotics. The literature supports that neonicotinoids have face-paced toxicokinetics and are unlikely to bioaccumulate in bees. I further reviewed current regulatory practices (LC50s and NOECs), and how a proxy for bioaccumulation can be derived using dose-dependence studies analysed with Haber’s Law. Next, I conducted laboratory experiments examining the usefulness of Haber’s Law for quantifying bioaccumulation using the neonicotinoids imidacloprid and thiamethoxam, and the known bioaccumulative phenylpyrazole, fipronil, as a positive control. Here, not only did I corroborate the literature review findings that neonicotinoids likely have face-paced toxicokinetics, I found evidence that fipronil has bioaccumulative properties, which underscores the usefulness of Haber’s Law in regulatory testing for bioaccumulation. Finally, I used 96-hour pulse-exposures to assess a proxy for toxicokinetic pace. Bees with pulsed exposures should have less injury than constant exposures if pesticides are easily cleared. Again, thiamethoxam and fipronil showed signs of differing toxicokinetic pace. These quantifiers could be used to fill a regulatory gap for bioaccumulation addressing toxicokinetic pace