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Risks of obstructive genitourinary birth defects in relation to trihalomethane and haloacetic acid exposures: expanding disinfection byproduct mixtures analyses using relative potency factors

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Abstract

Background

Some disinfection byproducts (DBPs) are teratogens based on toxicological evidence. Conventional use of predominant DBPs as proxies for complex mixtures may result in decreased ability to detect associations in epidemiological studies.

Objective

We assessed risks of obstructive genitourinary birth defects (OGDs) in relation to 12 DBP mixtures and 13 individual component DBPs.

Methods

We designed a nested registry-based case-control study (210 OGD cases; 2100 controls) in Massachusetts towns with complete quarterly 1999–2004 data on four trihalomethanes (THMs) and five haloacetic acids (HAAs). We estimated temporally-weighted average DBP exposures for the first trimester of pregnancy. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for OGD in relation to individual DBPs, unweighted mixtures, and weighted mixtures based on THM/HAA relative potency factors (RPF) from animal toxicology data for full-litter resorption, eye defects, and neural tube defects.

Results

We detected elevated aORs for OGDs for the highest of bromodichloromethane (aOR = 1.75; 95% CI: 1.15–2.65), dibromochloromethane (aOR = 1.71; 95% CI: 1.15–2.54), bromodichloroacetic acid (aOR = 1.56; 95%CI: 0.97–2.51), chlorodibromoacetic acid (aOR = 1.97, 95% CI: 1.23–3.15), and tribromoacetic acid (aOR = 1.90; 95%CI: 1.20–3.03). Across unweighted mixture sums, the highest aORs were for the sum of three brominated THMs (aOR = 1.74; 95% CI: 1.15–2.64), the sum of six brominated HAAs (aOR = 1.43; 95% CI: 0.89–2.31), and the sum of nine brominated DBPs (aOR = 1.80; 95% CI: 1.05–3.10). Comparing eight RPF-weighted to unweighted mixtures, the largest aOR differences were for two HAA metrics, which both were higher with RPF weighting; other metrics had reduced or minimally changed ORs in RPF-weighted models.

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Data availability

Data used in this analysis are based on birth records and birth defects registry data and are not publicly available.

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Disclaimer

The views expressed in this article are those of the authors and do not necessarily reflect the views or policies of the U.S. Environmental Protection Agency. This document has been reviewed in accordance with Agency policy and approved for publication.

Funding

JAK was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC. JAK was also supported in part by the National Institutes of Environmental Health Sciences (T32ES012870). AE was supported through the Oak Ridge Institute of Science and Education Research Participation Program (agreement no. DW8992376701) sponsored by the U.S. EPA. ZRN was supported through The National Academies, Research Associateship Programs sponsored by the U.S. EPA.

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Authors and Affiliations

  1. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA

    John A. Kaufman

  2. Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Cincinnati, OH, USA

    J. Michael Wright

  3. St. Elizabeth Physicians, Bellevue Primary Care, Bellevue, KY, USA

    Amanda Evans

  4. Rutgers School of Public Health, Department of Biostatistics and Epidemiology, Piscataway, NJ, USA

    Zorimar Rivera-Núñez

  5. Oak Ridge Institute of Science and Education, hosted by Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Cincinnati, OH, USA

    Amy Meyer

  6. University of Massachusetts, Amherst, MA, USA

    David A. Reckhow

  7. Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA

    Michael G. Narotsky

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  1. John A. Kaufman
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Contributions

JAK led the statistical analysis and led drafting and revision of the manuscript. JMW conceptualized the study, collected the data along with AM, and revised the manuscript. AE, ZRN, and AM prepared the analytic dataset and drafted analytic code in SAS. DAR contributed to development of the kinetic model used to predict four brominated haloacetic acids. MGN provided benchmark dose data for disinfection byproducts for use in relative potency factors, advised on the creation and use of relative potency factors, drafted text on methods for generation of relative potency factors, and revised the manuscript.

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Correspondence to John A. Kaufman.

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The authors declare no competing interests.

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This research was based on confidential birth records data that did not contain personal identifiable information; therefore, institutional review board approval was not obtained nor was informed consent necessary because potential risk was considered to be minimal and no direct contact with study subjects occurred.

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Kaufman, J.A., Wright, J.M., Evans, A. et al. Risks of obstructive genitourinary birth defects in relation to trihalomethane and haloacetic acid exposures: expanding disinfection byproduct mixtures analyses using relative potency factors. J Expo Sci Environ Epidemiol 34, 34–46 (2024). https://doi.org/10.1038/s41370-023-00595-1

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