PROJECT SUMMARY/ABSTRACTDrinking water contaminated by per- and polyfluoroalkyl substances (PFAS) has affected millions worldwide,including Michiganders at over 50 confirmed sites and 64 public water supplies. PFAS exposure has beenlinked to altered immune, endocrine, and liver function and to abnormal reproduction and development andpossibly carcinogenesis. The Agency for Toxic Substances and Disease Registry (ATSDR) multi-site healthstudy is an important step toward the long-term goal of characterizing the toxicity of PFAS along theseendpoints, and including Michigan markedly strengthens this national study. Michigan?s cohort will enableATSDR to capture a range of documented exposures to PFAS in areas where (1) we have a clearunderstanding of the source and extent of the exposure, essential to reconstructing historical levels of watercontamination; (2) the geographic scope of water contamination has been delineated; and (3) communitiesare supportive of engaging in activities to better understand the impact of these exposures on their individualand collective health. We will securely and effectively conduct data analysis and historical reconstruction,including water modeling, physiologically based pharmacokinetic (PBPK) modeling where appropriate, andstatistical analysis of the relationship between chemical exposure and health outcomes. The MichiganDepartment of Health and Human Services (MDHHS) and its Investigative Team will leverage existing publichealth infrastructure, including well-established relationships with the proposed communities, and ongoingPFAS exposure assessments and environmental investigations across the state to effectively and efficientlycomplete the core research protocol. We will expand on the core research by using newborn blood spot datato understand (1) historical and current infant PFAS blood levels and (2) relationships between newbornPFAS blood level and pregnancy complications (e.g., preeclampsia) and infant health effects (e.g., birthweight, thyroid function). This proposal represents a target sample population of 2,000 adults (male andfemale) and 600 children ages 4 to 17 years old allocated evenly among municipal and residential well usersat two sites. As stated in the core protocol, we will collect data from adults and children who have beenexposed to PFAS-contaminated water any time since 2005. Participants will attend a local clinic during whichthey will complete questionnaires, have anthropometric measurements taken, and provide blood and urinesamples. Consent for medical records abstraction will also be requested. Children will complete severalneurobehavioral assessments, and school records will be sought for analysis. The core protocol will befollowed exactly. In the investigator-initiated research, our investigative team will request consent fornewborn blood spot testing. We are positioned to fully involve these proposed communities and to implementfuture public health responses and clinical guidance in light of the Michigan and nationwide study resultscollected as part of this initiative. Not only will the proposed research advance scientific understanding ofPFAS toxicity, but it will also inform local, state, and national public health response to these contaminants.