Background: Uncertainty in exposure estimates from models can result in exposure measurement error and can potentially affect the validity of epidemiological studies. We recently used a suite of environmental models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations and assess the association with preeclampsia from 1990 through 2006 for the C8 Health Project participants.

Objectives: The aims of the current study are to evaluate impact of uncertainty in estimated PFOA drinking-water concentrations on estimated serum concentrations and their reported epidemiological association with preeclampsia.

Methods: For each individual public water district, we used Monte Carlo simulations to vary the year-by-year PFOA drinking-water concentration by randomly sampling from lognormal distributions for random error in the yearly public water district PFOA concentrations, systematic error specific to each water district, and global systematic error in the release assessment (using the estimated concentrations from the original fate and transport model as medians and a range of 2-, 5-, and 10-fold uncertainty).

Results: Uncertainty in PFOA water concentrations could cause major changes in estimated serum PFOA concentrations among participants. However, there is relatively little impact on the resulting epidemiological association in our simulations. The contribution of exposure uncertainty to the total uncertainty (including regression parameter variance) ranged from 5% to 31%, and bias was negligible.

Conclusions: We found that correlated exposure uncertainty can substantially change estimated PFOA serum concentrations, but results in only minor impacts on the epidemiological association between PFOA and preeclampsia.

Citation: Avanasi R, Shin HM, Vieira VM, Savitz DA, Bartell SM. 2016. Impact of exposure uncertainty on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population. Environ Health Perspect 124:126–132; http://dx.doi.org/10.1289/ehp.1409044

Address correspondence to S.M. Bartell, 2032 AIRB, Program in Public Health, University of California, Irvine, Irvine, CA 92697-3957 USA. Telephone: (949) 824-5919. E-mail: sbartell@uci.edu

Funding was provided by the National Institute of Environmental Health Sciences (21ES023120). Data collection and previous analyses were funded by the C8 Class Action Settlement Agreement (Circuit Court of Wood County, West Virginia).

The content of this publication is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

The authors declare they have no actual or potential competing financial interests.

Received: 5 August 2014 Accepted: 12 June 2015 Advance Publication: 19 June 2015 Final Publication: 1 January 2016

Note to readers with disabilities: EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact ehp508@niehs.nih.gov . Our staff will work with you to assess and meet your accessibility needs within 3 working days.