Developmental VOC Exposure in Zebrafish: Toxic Mechanisms and Biomarkers

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).

Grant Number: 5P42ES030991-04
NIH Institute/Center: NIH
Principal Investigator: Tracie Baker