Tetrachloroethylene (PCE) is a solvent commonly used in dry cleaning, textile processing and metal degreasing. Because most of its use occurs in uncontrolled occupational settings, PCE is a common contaminant of U.S. public drinking water supplies and Superfund sites. While concerns about PCE are based mainly on its carcinogenicity and neurotoxicity, there is also mounting animal and human evidence that prenatal exposure to PCE increases the risk of birth defects. While these findings raise concerns for pregnant women, this body of literature is small and has weaknesses that hamper firm conclusions. Thus, we propose to conduct a population-based case-control study specifically designed to overcome the limitations of prior investigations. Building upon our prior Superfund research, the proposed study will test the hypothesis that prenatal exposure to PCE-contaminated drinking water is associated with oral clefts, neural tube, and cardiac defects. The study will identify 400 cases of oral clefts, 400 cases of neural tube defects, 400 cases of cardiac defects and 800 unaffected controls using live birth, fetal death, and medical records from Massachusetts and Rhode Island during the period 1969-1990. The source population includes approximately 279,269 live births and 1,954 stillbirths in 42 cities and towns whose public drinking water supplies were contaminated with PCE during this 22-year period. Case and control mothers will be sent a self-administered questionnaire to gather information on prenatal residential locations and demographic, behavioral and medical confounding variables. Data on environmental exposures that are potential confounders will be collected from historical records. Prenatal exposure to PCE-contaminated drinking water will be estimated using a leaching and transport exposure model developed and validated during our prior Superfund study. A quantitative bias analysis will be conducted to determine the impact of misclassification on the study results. Exposure assessment software and historical PCE contaminant levels will be shared with local water utilities and study findings will be communicated to local communities.

Public Health Relevance

The proposed study addresses public health and Superfund goals to: (1) improve our understanding of the relationship between a low-level environmental exposure and disease in a vulnerable population in a community setting, (2) provide evidence to enhance decision-making regarding PCE exposure reduction, and (3) respond to the need for research on the health consequences of TCE, a solvent whose chemical structure, metabolism, and health effects are closely related to those of PCE.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
Application #
Study Section
Special Emphasis Panel (ZES1-JAB-J)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Boston University
United States
Zip Code
Townley, Ian K; Karchner, Sibel I; Skripnikova, Elena et al. (2017) Sequence and functional characterization of hypoxia-inducible factors, HIF1?, HIF2?a, and HIF3?, from the estuarine fish, Fundulus heteroclitus. Am J Physiol Regul Integr Comp Physiol 312:R412-R425
Whitehead, Andrew; Clark, Bryan W; Reid, Noah M et al. (2017) When evolution is the solution to pollution: Key principles, and lessons from rapid repeated adaptation of killifish (Fundulus heteroclitus) populations. Evol Appl 10:762-783
Holland, Erika B; Goldstone, Jared V; Pessah, Isaac N et al. (2017) Ryanodine receptor and FK506 binding protein 1 in the Atlantic killifish (Fundulus heteroclitus): A phylogenetic and population-based comparison. Aquat Toxicol 192:105-115
Hahn, Mark E; Karchner, Sibel I; Merson, Rebeka R (2017) Diversity as Opportunity: Insights from 600 Million Years of AHR Evolution. Curr Opin Toxicol 2:58-71
Martinez, Andres; Hadnott, Bailey N; Awad, Andrew M et al. (2017) Release of Airborne Polychlorinated Biphenyls from New Bedford Harbor Results in Elevated Concentrations in the Surrounding Air. Environ Sci Technol Lett 4:127-131
Parente, Thiago E; Moreira, Daniel A; Magalhães, Maithê G P et al. (2017) The liver transcriptome of suckermouth armoured catfish (Pterygoplichthys anisitsi, Loricariidae): Identification of expansions in defensome gene families. Mar Pollut Bull 115:352-361
Butler, Lindsey J; Janulewicz, Patricia A; Carwile, Jenny L et al. (2017) Childhood and adolescent fish consumption and adult neuropsychological performance: An analysis from the Cape Cod Health Study. Neurotoxicol Teratol 61:47-57
Reid, Noah M; Jackson, Craig E; Gilbert, Don et al. (2017) The landscape of extreme genomic variation in the highly adaptable Atlantic killifish. Genome Biol Evol :
Vieira, Verónica M; Villanueva, Carolina; Chang, Jenny et al. (2017) Impact of community disadvantage and air pollution burden on geographic disparities of ovarian cancer survival in California. Environ Res 156:388-393
Hoffman, Kate; Weisskopf, Marc G; Roberts, Andrea L et al. (2017) Geographic Patterns of Autism Spectrum Disorder Among Children of Participants in Nurses' Health Study II. Am J Epidemiol 186:834-842

Showing the most recent 10 out of 377 publications