SUMMARY Pollution has become an increasing problem with negative implications for human health. The heavy metals lead, hexavalent chromium, and cadmium have contaminated sites throughout the United States. The National Toxicology Program (NTP) has focused on investigating the toxicological effects using a single genetic background, B6C3F1. This leaves unanswered questions about how genetic background affects dose-response to these toxicants. In collaboration with members of the Texas A&M Center for Environmental Health Sciences (TICER) thematic areas of Stressors to Responses and Individuals to Populations, the genetic background affects metal deposition after single metal oral exposure to lead, hexavalent chromium, or cadmium will be investigated as an exemplar that can connect these thematic areas. To model diversity in the human population, strains from the Collaborative Cross (CC) mouse genetic reference population will be used. Using preliminary data from a large CC screen for lead deposition, four CC strains per metal treatment will be used in a standard NTP type 14-day exposure to address differences in the deposition, molecular and cellular mechanism of toxicity, and microbiome dysbiosis of lead acetate, sodium dichromate, and cadmium chloride. To better model those exposed in the US, mice will be maintained on a high-fat, high-carbohydrate American previously formulated to model the average dietary consumption of Americans. Low and high doses of these metals that model human exposures will be administered by drinking water. In addition to benefiting TICER members by demonstrating how two diverse thematic areas can be integrated, this study will provide an outstanding training platform for a scientist in training to increase the environmental health workforce and will better inform the development of more reliable toxicity ranges and establish the foundation for mechanistic studies underlying differential response to heavy metals. Additionally, the candidate will gain community engagement experience by working with the TICER Community Engagement Core to help educate communities of concern on the impact of heavy metal exposure and how TICER is addressing the health impacts. This will also allow the candidate to gain career experiences in community engagement.