Tackling Arctic toxicology challenges using in vitro and in silico approaches to characterize and predict organism-level effects of chemical stressors

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Hundreds of thousands of chemicals are used globally and thousands of new ones produced every year. Many of these enter the environment and cause adverse effects in humans and wildlife. Nowhere is this more evident than in the Arctic where high trophic feeding populations like Indigenous communities and marine mammals can biomagnify chemicals to alarming levels. The Stockholm Convention currently regulates 35 chemical groups known for their persistence, bioaccumulation, long-range transport, and toxicity (PBLT). Using modeling approaches, recent studies have identified over 3000 PBLT chemicals that threaten the Arctic, termed Chemicals of Emerging Arctic Concern (CEACs). Most of these are unmonitored and their toxicity is unknown. Arctic (and other) toxicologists often rely on laboratory animal toxicity data, though these come with a slew of logistical, monetary, and ethical constraints as millions of animals are killed yearly. As such, a major transformation in chemical risk assessment is urgently needed. 21st century toxicology will need to adopt in vitro and in silico methods, combined with new technologies like toxicogenomics, to provide animal-free, rapid, and cost-effective toxicity data. The long-term objective of my research program is to develop strategies for better chemical management and improve wildlife chemical risk assessment in the Arctic. I will address current knowledge gaps and constraints in Arctic toxicology through adoption of a unique combination of in vitro experiments, field-based wildlife studies, and mechanistic toxicokinetic and toxicodynamic (TKTD) modeling. My short-term objectives are: 1) Establish an in vitro toxicity testing framework and assess the toxicity of legacy chemicals and CEACs; 2) Develop a mechanistic TKTD modeling framework to extrapolate in vitro effects of legacy chemicals and CEACs; and 3) Investigate the in vitro effects of legacy chemicals and CEACs in Arctic wildlife. This research will establish the next generation of Arctic chemical and wildlife risk assessment that minimizes animal testing and maximizes mechanistic understanding of toxicity. This work fills an important knowledge gap for risk assessors and regulators in the Arctic and abroad that lack toxicity data for CEACs. Specifically, this research program looks to build up capacity in Canada in the use of mechanistic energy budget modeling for chemical risk assessment. The multidisciplinary approach taken offers great opportunities to yield new knowledge and advance our understanding of stressor impacts across biological scales and environments. Finally, this program will support the training of 13 HQP in highly sought-after skillsets in laboratory work, fieldwork, statistical analysis, and computer modeling. HQP will develop transferable skills in critical thinking, quantitative analysis, communication, and leadership through their research and participation in knowledge mobilization through publications and conference presentations.