Summary/Abstract: Anthropogenic Volatile Organic Compounds (VOCs) have emerged as high priority environmental contaminants due to ubiquitous urban exposure via industrial exhaust, fuel refineries, and vehicle exhaust, as well as VOC contamination at an estimated 78% of Superfund sites. Residents in urban areas are disproportionately exposed to VOCs as a result of indoor vapor intrusion, tap water, ingestion of contaminated fish, and ambient outdoor exposure. Inhalation, ingestion, and dermal adsorption from indoor and outdoor sources are routes for human exposure, and at-risk communities are often chronically exposed to complex mixtures of VOCs. Varied adverse health impacts associated with VOC exposure involve the respiratory, cardiovascular, renal, hepatic, endocrine, immune, and nervous systems. Studies also suggest that chronic, maternal VOC exposure is linked to birth defects and preterm birth. Nonetheless, these health risks remain ill-defined. The Center for Leadership in Environmental Awareness and Research (CLEAR) seeks to reduce the impacts of environmental contaminants on both public and environmental health, focusing on the alarming rate of preterm births in Detroit. Our hypothesis is that exposure to VOCs at environmentally-relevant concentrations and mixtures will impair development, immune function, and reproductive health in zebrafish, an NIH-accepted model organism. The development of innovative, high-throughput techniques will enable the CLEAR B1 team to perform novel developmental, reproductive, neurobehavioral, immune, and multigenerational bioassays to evaluate adverse phenotypic effects of exposure to six VOCs at various concentrations (Aim 1), similarly, identify effects of exposure to VOC mixtures (Aim 2), and employ molecular techniques to identify transcriptomic and epigenetic pathways, as well as rank potential biomarkers (by sensitivity), relevant to VOC exposure and specific biological effects (Aim 3). Using data from Projects E1, E2, B3, and the CEC, we will focus our experiments on environmentally-relevant VOC concentrations and mixtures found in Detroit and at known Superfund sites. The proposed research is significant because the results are expected to fill knowledge gaps in the field at basic and applied levels and have a positive translational impact by expanding the depth of our understanding regarding health impacts of individual VOCs and VOC mixtures, critical developmental windows for these adverse health impacts and biomarkers of effect, and mechanisms for environmentally-influenced, adult-onset and multigenerational disease. These results will be shared with the research training, data analysis, and chemical analysis cores to advance the development of evidence-based strategies to prevent and treat environmentally-induced disease. Ultimately, these strategies will be used by the community engagement core to enact VOC prevention and intervention measures to improve the health of mothers and children in Detroit (Figure 1).

Project Narrative: This project will provide a better understanding of reproductive, developmental, immunological, neurobehavioral, and multigenerational health effects of a wide-range of individual VOCs and VOC mixtures in zebrafish, including combinations and concentrations of VOC contamination similar to those found in the homes and environments of our target population in Detroit, MI. CLEAR Project B1 will identify specific genetic and epigenetic biomarkers associated with each VOC exposure and their potential impacts on subsequent generations. Results will be utilized by the Community Engagement Core to aid the community, policy-makers, physicians, and other stakeholders to implement prevention and intervention measures to protect public health.