Behavioral Alterations Following Exposure to a Mixture of Lead and Atrazine During Early Development in the Zebrafish Model System

Lead (Pb) and atrazine (ATZ) are hazardous environmental toxicants that can exist as a mixture in potable water. Numerous single chemical studies on Pb and ATZ support adverse health outcomes, including neurotoxicity, but mixture studies are limited. Th e aim of this study is to test the hypothesis that Pb and ATZ mixtures result in a greater than additive toxicity, causing increased adverse health outcomes than single chemical exposures. Th e zebrafi sh model system was exposed to 3 or 30 ppb (µg/L) ATZ, 10 ppb (equivalent to 0.1 µg/dL) or 100 ppb Pb, along with mixtures of each beginning at 1 hour postfertilization (hpf) and continuing through 120 hpf. A visual motor response behavioral assay was then conducted using the Noldus DanioVision. Th e visual motor response assay tracks locomotor movement over fi ve alternating periods of dark and light. Th e behavior data was analyzed by phase with a repeated measures ANOVA. Th e 10 ppb Pb mixture behavior data showed signifi cant hypoactivity in the 10 ppb Pb, 30 ppb ATZ, 3 ppb ATZ/10 ppb Pb, and 30 ppb ATZ/10 ppb Pb treatments for all parameters in multiple phases ( p < 0.05). Th e 100 ppb Pb mixture behavior data also showed signifi cant hypoactivity in the 100 ppb Pb and 30 ppb ATZ treatment groups, along with hypoactivity in both mixture treatment groups ( p < 0.05). Additionally, the 3 ppb ATZ treatment group had hyperactivity in the third dark phase ( p < 0.05). Th ese data align with past single chemical behavior studies and indicate a greater than additive mixture toxicity. zebrafish model system. Her dissertation has three main components, including predictive mixture modeling, molecular and cerebral vasculature development after mixture exposure, and generation of a disease model of neurodegener-ation using CRISPR- Cas9, a gene- editing technology. model system. These studies are investigating a developmental origin of adult disease pathogenesis with a specific focus on neuroendocrine dysfunction, neurodegenerative diseases, and cancer with a goal of understanding the role of exposure to the environmental chemicals in these adverse health outcomes. Behavioral Alterations following Exposure to a Mixture of Lead and Atrazine during Early Development in the Zebrafish Model System