Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Comparison of Trihalomethane exposure assessment metrics in epidemiologic analyses of reproductive and developmental outcomes

Journal of Exposure Science & Environmental Epidemiology volume 34, pages 115–125 (2024)Cite this article

Abstract

Background

Researchers have developed exposure assessment metrics for disinfection by-products (DBPs) utilizing drinking water monitoring data and accounting for spatial and temporal variability, water consumption, and showering and bathing time with an expectation of decreasing exposure misclassification compared to the use of measured concentrations at public water supply (PWS) monitoring locations alone.

Objective

We used exposure data collected for a previous study of DBPs to evaluate how different sources of information impact trihalomethane (THM) exposure estimates.

Methods

We compared gestational exposure estimates to THMs based on water utility monitoring data alone, statistical imputation of daily concentrations to incorporate temporal variability, and personal water consumption and use (bathing and showering). We used Spearman correlation coefficients and ranked kappa statistics to compare exposure classifications.

Results

Exposure estimates based on measured or imputed daily THM concentrations, self-reported consumption, or bathing and showering differed substantially from estimates based solely on concentrations from PWS quarterly monitoring reports. Ranked exposure classifications, high to low quartiles or deciles, were generally consistent across each exposure metric (i.e., a subject with “high” exposure based on measured or imputed THM concentrations generally remained in the “high” category across exposure metrics.) The measured concentrations and imputed daily (i.e., spline regression) concentrations were highly correlated (r = 0.98). The weighted kappa statistics comparing exposure estimates using different exposure metrics ranged from 0.27 to 0.89, with the highest values for the ingestion + bathing/showering metrics compared to metrics for bathing/showering only (0.76 and 0.89). Bathing and showering contributed the most to “total” THM exposure estimates.

Impact Statement

We compare exposure metrics capturing temporal variability and multiple estimates of personal THM exposure with THM concentrations from PWS monitoring data. Our results show exposure estimates based on imputed daily concentrations accounting for temporal variability were very similar to the measured THM concentrations. We observed low agreement between imputed daily concentrations and ingestion-based estimates. Considering additional routes of exposure (e.g., inhalation and dermal) slightly increased agreement with the measured PWS exposure estimate in this population. Overall, the comparison of exposure assessment metrics allows researchers to understand the added value of additional data collection for future epidemiologic analyses of DBPs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Agreement between ranked quartiles of prenatal THM4 exposure metrics.

Similar content being viewed by others

Data availability

All data used in these analyses were collected under the auspices of the National Birth Defects Prevention Study (NBDPS). Data that CDC collects or holds related to the NBDPS is made available for data sharing within a year after the data are evaluated for quality and shared with any partners in data collection activity. Because NBDPS data contain PII, NBDPS data are not released publicly. Instead, they are available via a special use agreement. Qualified researchers can be granted access to NBDPS data for analysis though collaboration with one of the Centers for Birth Defects Research and Prevention. The procedure for applying for access to NBDPS data can be found on the NBDPS Public Access Procedures web site: https://www.cdc.gov/ncbddd/birthdefects/nbdps-public-access-procedures.html.

References

  1. Colman J, Rice GE, Wright JM, Hunter ES, Teuschler LK, Lipscomb JC, et al. Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action. Toxicol Appl Pharmacol. 2011;254:100–26.

    Article  CAS  PubMed  Google Scholar 

  2. Klinefelter GR, Hunter ES, Narotsky M. Reproductive and developmental toxicity associated with disinfection by-products of drinking water. Microbial pathogens and disinfection by-products of drinking water. 2001;309–33.

  3. Narotsky MG, Best DS, McDonald A, Godin EA, Hunter ES, Simmons JE. Pregnancy loss and eye malformations in offspring of F344 rats following gestational exposure to mixtures of regulated trihalomethanes and haloacetic acids. Reprod Toxicol. 2011;31:59–65.

    Article  CAS  PubMed  Google Scholar 

  4. Legay C, Rodriguez MJ, Sérodes JB, Levallois P. Estimation of chlorination by-products presence in drinking water in epidemiological studies on adverse reproductive outcomes: a review. Sci Total Environ. 2010;408:456–72.

    Article  CAS  PubMed  Google Scholar 

  5. Nieuwenhuijsen MJ, Martinez D, Grellier J, Bennett J, Best N, Iszatt N, et al. Chlorination disinfection by-products in drinking water and congenital anomalies: review and meta-analyses. Environ Health Perspect. 2009;117:1486–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Summerhayes RJ, Rahman B, Morgan G, Beresin GG, Moreno C, Wright JM. Meta-analysis of small for gestational age births and disinfection byproduct exposures. Environ Res. 2021;196:110280.

  7. Wright JM, Evans A, Kaufman JA, Rivera-Núñez Z, Narotsky MG. Disinfection by-product exposures and the risk of specific cardiac birth defects. Environ Health Perspect. 2017;125:269–77.

    Article  CAS  PubMed  Google Scholar 

  8. Säve-Söderbergh M, Toljander J, Donat-Vargas C, Åkesson A. Drinking water disinfection by-products and congenital malformations: A Nationwide register-based prospective study. Environ Health Perspect. 2021;129:097012.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Arbuckle TE, Hrudey SE, Krasner SW, Nuckols JR, Richardson SD, Singer P, et al. Assessing exposure in epidemiologic studies to disinfection by-products in drinking water: report from an international workshop. Environ Health Perspect. 2002;110:53–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bove F, Shim Y, Zeitz P. Drinking water contaminants and adverse pregnancy outcomes: a review. Environ Health Perspect. 2002;110:61–74.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Nieuwenhuijsen MJ, Toledano MB, Elliott P. Uptake of chlorination disinfection by-products; a review and a discussion of its implications for exposure assessment in epidemiological studies. J Exposure Sci Environ Epidemiol. 2000;10:586–99.

    Article  CAS  Google Scholar 

  12. Reif JS, Hatch MC, Bracken M, Holmes LB, Schwetz BA, Singer PC. Reproductive and developmental effects of disinfection by-products in drinking water. Environ health Perspect. 1996;104:1056–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Jones AQ, Dewey CE, Doré K, Majowicz SE, McEwen SA, Waltner-Toews D. Exposure assessment in investigations of waterborne illness: a quantitative estimate of measurement error. Epidemiol Perspect Innov. 2006;3:1–8.

    Article  Google Scholar 

  14. Luben TJ, Nuckols JR, Mosley BS, Hobbs C, Reif JS. Maternal exposure to water disinfection by-products during gestation and risk of hypospadias. Occup Environ Med. 2008;65:420–9.

    Article  CAS  PubMed  Google Scholar 

  15. Symanski E, Savitz DA, Singer PC. Assessing spatial fluctuations, temporal variability, and measurement error in estimated levels of disinfection by-products in tap water: implications for exposure assessment. Occup Environ Med. 2004;61:65–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Whitaker H, Nieuwenhuijsen MJ, Best N, Fawell J, Gowers A, Elliot P. Description of trihalomethane levels in three UK water suppliers. J Exposure Sci Environ Epidemiol. 2003;13:17–23.

    Article  CAS  Google Scholar 

  17. Evans AM, Wright JM, Meyer A, Rivera-Núñez Z. Spatial variation of disinfection by-product concentrations: Exposure assessment implications. Water Res. 2013;47:6130–40.

    Article  CAS  PubMed  Google Scholar 

  18. Parvez S, Rivera-Núñez Z, Meyer A, Wright JM. Temporal variability in trihalomethane and haloacetic acid concentrations in Massachusetts public drinking water systems. Environ Res. 2011;111:499–509.

    Article  CAS  PubMed  Google Scholar 

  19. Legay C, Rodriguez MJ, Sérodes JB, Levallois P. The assessment of population exposure to chlorination by-products: a study on the influence of the water distribution system. Environ Health. 2010;9:59.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Villanueva CM, Gagniere B, Monfort C, Nieuwenhuijsen MJ, Cordier S. Sources of variability in levels and exposure to trihalomethanes. Environ Res. 2007;103:211–20.

    Article  CAS  PubMed  Google Scholar 

  21. Wright JM, Murphy PA, Nieuwenhuijsen MJ, Savitz DA. The impact of water consumption, point-of-use filtration and exposure categorization on exposure misclassification of ingested drinking water contaminants. Sci Total Environ. 2006;366:65–73.

    Article  CAS  PubMed  Google Scholar 

  22. Nuckols JR, Ashley DL, Lyu C, Gordon SM, Hinckley AF, Singer P. Influence of tap water quality and household water use activities on indoor air and internal dose levels of trihalomethanes. Environ Health Perspect. 2005;113:863–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hinckley A, Bachand A, Nuckols J, Reif J. Identifying public water facilities with low spatial variability of disinfection by-products for epidemiological investigations. Occup Environ Med. 2005;62:494–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Nuckols J, Langlois P, Lynberg M, Luben T Linking geographic water utility data with study participant residences from the National Birth Defects Prevention Study. Denver, CO: American Water Works Association. 2004.

  25. Waller K, Swan SH, Windham GC, Fenster L. Influence of exposure assessment methods on risk estimates in an epidemiologic study of total trihalomethane exposure and spontaneous abortion. J Exposure Sci Environ Epidemiol. 2001;11:522–31.

    Article  CAS  Google Scholar 

  26. Dodds L, King W, Woolcott C, Pole J. Trihalomethanes in public water supplies and adverse birth outcomes. Epidemiology. 1999;10:233–7.

  27. Dodds L, King W. Relation between trihalomethane compounds and birth defects. Occup Environ Med. 2001;58:443–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Golfinopoulos SK, Arhonditsis GB. Multiple regression models: a methodology for evaluating trihalomethane concentrations in drinking water from raw water characteristics. Chemosphere 2002;47:1007–18.

    Article  CAS  PubMed  Google Scholar 

  29. King WD, Dodds L, Armson BA, Allen AC, Fell DB, Nimrod C. Exposure assessment in epidemiologic studies of adverse pregnancy outcomes and disinfection byproducts. J Exposure Sci Environ Epidemiol. 2004;14:466–72.

    Article  CAS  Google Scholar 

  30. Weyer P, Rhoads A, Suhl J, Luben TJ, Conway KM, Langlois PH, et al. Drinking water disinfection byproducts and risk of orofacial clefts in the National Birth Defects Prevention Study. Birth defects Res. 2018;110:1027–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Zaganjor I, Luben TJ, Desrosiers TA, Keil AP, Engel LS, Michalski AM, et al. Maternal Exposure to Disinfection By-Products and Risk of Hypospadias in the National Birth Defects Prevention Study (2000–2005). Int J Environ Res public health. 2020;17:9564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Savitz DA, Singer PC, Hartmann KE. Drinking water disinfection by-products and pregnancy outcome: AWWA Research Foundation; 2005.

  33. Villanueva CM, Gracia-Lavedán E, Ibarluzea J, Santa Marina L, Ballester F, Llop S, et al. Exposure to trihalomethanes through different water uses and birth weight, small for gestational age, and preterm delivery in Spain. Environ health Perspect. 2011;119:1824–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Shaffer RM, Luben TJ, Wright JM, editors. A Review of Exposure Assessment Methods Utilized in Studies of Disinfection Byproducts (DBPs) and Birth Defects 2021.

  35. Zaganjor I, Keil AP, Luben TJ, Desrosiers TA, Engel LS, Reefhuis J, et al. Is maternal employment site a source of exposure misclassification in studies of environmental exposures and birth outcomes? A simulation-based bias analysis of haloacetic acids in tap water and hypospadias. Environ Epidemiol. 2022;6:e207.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Reefhuis J, Gilboa SM, Anderka M, Browne ML, Feldkamp ML, Hobbs CA, et al. The national birth defects prevention study: a review of the methods. Birth Defects Res Part A: Clin Mol Teratol. 2015;103:656–69.

    Article  CAS  Google Scholar 

  37. Moore KL, Persaud TVN, Torchia MG. Before we are born E-Book: Essentials of embryology and birth defects with student consult online access: Elsevier Health Sciences; 2015.

  38. Hinckley AF, Bachand AM, Reif JS. Late pregnancy exposures to disinfection by-products and growth-related birth outcomes. Environ Health Perspect. 2005;113:1808–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Rothman KJ, Greenland S, Lash TL. Modern epidemiology: Lippincott Williams & Wilkins; 2008.

  40. Kuo H-W, Chiang T-F, Lo I-I, Lai J-S, Chan C-C, Wang J-D. VOC concentration in Taiwan’s household drinking water. Sci Total Environ. 1997;208:41–7.

    Article  CAS  PubMed  Google Scholar 

  41. Wu WW, Benjamin MM, Korshin GV. Effects of thermal treatment on halogenated disinfection by-products in drinking water. Water Res. 2001;35:3545–50.

    Article  CAS  PubMed  Google Scholar 

  42. Stalter D, O’Malley E, Von Gunten U, Escher BI. Point-of-use water filters can effectively remove disinfection by-products and toxicity from chlorinated and chloraminated tap water. Environ Sci: Water Res Technol. 2016;2:875–83.

    CAS  Google Scholar 

  43. Kenyon EM, Eklund C, Leavens T, Pegram RA. Development and application of a human PBPK model for bromodichloromethane to investigate the impacts of multi‐route exposure. J Appl Toxicol. 2016;36:1095–111.

    Article  CAS  PubMed  Google Scholar 

  44. Kerger B, Schmidt C, Paustenbach D. Assessment of airborne exposure to trihalomethanes from tap water in residential showers and baths. Risk Anal. 2000;20:637–52.

    Article  CAS  PubMed  Google Scholar 

  45. Toroz I, Uyak V. Seasonal variations of trihalomethanes (THMs) in water distribution networks of Istanbul City. Desalination 2005;176:127–41.

    Article  CAS  Google Scholar 

  46. Keegan T, Whitaker H, Nieuwenhuijsen M, Toledano M, Elliott P, Fawell J, et al. Use of routinely collected data on trihalomethane in drinking water for epidemiological purposes. Occup Environ Med. 2001;58:447–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lynberg M, Nuckols J, Langlois P, Ashley D, Singer P, Mendola P, et al. Assessing exposure to disinfection by-products in women of reproductive age living in Corpus Christi, Texas, and Cobb county, Georgia: descriptive results and methods. Environ Health Perspect. 2001;109:597–604.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Gallagher MD, Nuckols JR, Stallones L, Savitz DA. Exposure to trihalomethanes and adverse pregnancy outcomes. Epidemiology. 1998;9:484–9.

  49. Singer PC, Obolensky A, Greiner A. DBPs in chlorinated North Carolina drinking waters. J‐Am Water Works Assoc. 1995;87:83–92.

    Article  CAS  Google Scholar 

  50. Rodriguez MJ, Sérodes J-B. Spatial and temporal evolution of trihalomethanes in three water distribution systems. Water Res. 2001;35:1572–86.

    Article  CAS  PubMed  Google Scholar 

  51. Guilherme S, Rodriguez MJ. Short-term spatial and temporal variability of disinfection by-product occurrence in small drinking water systems. Sci Total Environ. 2015;518-519:280–9.

    Article  CAS  PubMed  Google Scholar 

  52. Wright JM, Bateson TF. A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification. J Exposure Sci Environ Epidemiol. 2005;15:212–6.

    Article  CAS  Google Scholar 

  53. Rossman LA, Clark RM, Grayman WM. Modeling chlorine residuals in drinking-water distribution systems. J Environ Eng. 1994;120:803–20.

    Article  CAS  Google Scholar 

  54. Richter W, Hart TF, Luben T, Freud S, Nuckols JR. Evaluation of two methods of interpolating quarterly trihalomethane levels between sampling dates. J exposure Sci Environ Epidemiol. 2009;19:405–13.

    Article  CAS  Google Scholar 

  55. Whitaker H, Best N, Nieuwenhuijsen MJ, Wakefield J, Fawell J, Elliott P. Modelling exposure to disinfection by-products in drinking water for an epidemiological study of adverse birth outcomes. J Exposure Sci Environ Epidemiol. 2005;15:138–46.

    Article  CAS  Google Scholar 

  56. Backer LC, Ashley DL, Bonin MA, Cardinali FL, Kieszak SM, Wooten JV. Household exposures to drinking water disinfection by-products: Whole blood trihalomethane levels. J Exposure Sci Environ Epidemiol. 2000;10:321–6.

    Article  CAS  Google Scholar 

  57. Charisiadis P, Andra SS, Makris KC, Christodoulou M, Christophi CA, Kargaki S, et al. Household cleaning activities as noningestion exposure determinants of urinary trihalomethanes. Environ Sci Technol. 2014;48:770–80.

    Article  CAS  PubMed  Google Scholar 

  58. Gordon SM, Brinkman MC, Ashley DL, Blount BC, Lyu C, Masters J, et al. Changes in breath trihalomethane levels resulting from household water-use activities. Environ health Perspect. 2006;114:514–21.

    Article  CAS  PubMed  Google Scholar 

  59. Lévesque B, Ayotte P, LeBlanc A, Dewailly É, Prud’Homme D, Lavoie R, et al. Evaluation of dermal and respiratory chloroform exposure in humans. Environ health Perspect. 1994;102:1082–7.

    PubMed  PubMed Central  Google Scholar 

  60. Beer TW. Terminal digit preference: Beware of Benford’s law. J Clin Pathol. 2009;62:192.

    Article  CAS  PubMed  Google Scholar 

  61. Hayes SJ. Does terminal digit preference occur in pathology? J Clin Pathol. 2008;61:975.

    Article  CAS  PubMed  Google Scholar 

  62. Lourencetti C, Grimalt JO, Marco E, Fernandez P, Font-Ribera L, Villanueva CM, et al. Trihalomethanes in chlorine and bromine disinfected swimming pools: Air-water distributions and human exposure. Environ Int. 2012;45:59–67.

    Article  CAS  PubMed  Google Scholar 

  63. Savitz DA, Singer PC, Herring AH, Hartmann KE, Weinberg HS, Makarushka C. Exposure to drinking water disinfection by-products and pregnancy loss. Am J Epidemiol. 2006;164:1043–51.

    Article  PubMed  Google Scholar 

  64. Whitaker HJ, Nieuwenhuijsen MJ, Best NG. The relationship between water concentrations and individual uptake of chloroform: a simulation study. Environ Health Perspect. 2003;111:688–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Da Silva JT, Seminowicz DA. Neuroimaging of pain in animal models: a review of recent literature. Pain Rep. 2019;4:e732.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Iszatt N, Nieuwenhuijsen MJ, Nelson P, Elliott P, Toledano MB. Water consumption and use, trihalomethane exposure, and the risk of hypospadias. Pediatrics 2011;127:e389–e97.

    Article  PubMed  Google Scholar 

  67. Haddad S, Tardif G-C, Tardif R. Development of physiologically based toxicokinetic models for improving the human indoor exposure assessment to water contaminants: trichloroethylene and trihalomethanes. J Toxicol Environ Health, Part A. 2006;69:2095–136.

    Article  CAS  Google Scholar 

  68. Yang P, Cao W-C, Zhou B, Zheng T-Z, Deng Y-L, Luo Q, et al. Urinary biomarker of prenatal exposure to disinfection byproducts, maternal genetic polymorphisms in CYP2E1 and GSTZ1, and Birth Outcomes. Environ Sci Technol. 2019;53:12026–34.

    Article  CAS  PubMed  Google Scholar 

  69. Zhou B, Yang P, Gong Y-J, Zeng Q, Lu W-Q, Miao X-P. Effect modification of CPY2E1 and GSTZ1 genetic polymorphisms on associations between prenatal disinfection by-products exposure and birth outcomes. Environ Pollut. 2018;243:1126–33.

    Article  CAS  PubMed  Google Scholar 

  70. Villanueva CM, Castaño-Vinyals G, Moreno V, Carrasco-Turigas G, Aragonés N, Boldo E, et al. Concentrations and correlations of disinfection by-products in municipal drinking water from an exposure assessment perspective. Environ Res. 2012;114:1–11.

    Article  CAS  PubMed  Google Scholar 

  71. Furst KE, Bolorinos J, Mitch WA. Use of trihalomethanes as a surrogate for haloacetonitrile exposure introduces misclassification bias. Water Res. X 2021;11:100089.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Savitz DA. Invited commentary: Biomarkers of exposure to drinking water disinfection by-products—are we ready yet? Am J Epidemiol. 2012;175:276–8.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This project was supported through Centers for Disease Control and Prevention cooperative agreements under PA #96043, PA #02081, and FOA #DD09-001 to the Centers for Birth Defects Research and Prevention participating in the National Birth Defects Prevention Study (NBDPS), and the Arkansas Center for Birth Defects Prevention Study, grant/award number # U01DD00049. This study was funded in part by the Battelle Memorial Institute (PO 182124Mod 02). The funding sources were not involved in study design, data collection, analyses or interpretation of the data, in writing the report or in the decision to submit the paper for publication.

We thank the Arkansas Center for Health Statistics at the Arkansas Department of Health and the Arkansas Reproductive Health Monitoring System for providing data on cases and controls and the Environmental Health Services Division at the Arkansas Department of Health for providing community water system monitoring data for trihalomethanes. We thank Drs. Alison Krajewski and Andrey Egorov for early comments on the draft manuscript.

Author information

Authors and Affiliations

  1. Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency. RTP, NC, Washington, DC, Cincinnati, OH, USA

    Thomas J. Luben, Rachel M. Shaffer & J. Michael Wright

  2. Center for Computational Toxicology and Exposure, Office of Research and Development, U.S. Environmental Protection Agency, RTP, RTP, NC, USA

    Elaina Kenyon

  3. Arkansas Center for Birth Defects Research and Prevention and the Department of Epidemiology, Fay. W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Wendy N. Nembhard & Kari A. Weber

  4. Colorado State University, Fort Collins, CO, USA; JRN Environmental Health Sciences, LTD, North Bethesda, MD, USA

    John Nuckols

Authors
  1. Thomas J. Luben
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel M. Shaffer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elaina Kenyon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wendy N. Nembhard
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kari A. Weber
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. John Nuckols
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J. Michael Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

TJL, RMS, and JMW conceived and designed the study, WNN and KW provided the analytic sample and specified relevant exposure variables, EK developed PBPK-based exposure metrics, and TJL conducted the analyses. TJL, RMS, JMW, and JN interpreted the results. TJL, RMS EK, and JMW prepared the draft manuscript. WNN, KW, and JN reviewed the manuscript and provided substantial feedback. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Thomas J. Luben.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethical approval

This study protocol was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill UNC IRB Number: 05-1420). The EPA’s Human Subjects Research Officer also reviewed and approved this work (HSR-001255).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luben, T.J., Shaffer, R.M., Kenyon, E. et al. Comparison of Trihalomethane exposure assessment metrics in epidemiologic analyses of reproductive and developmental outcomes. J Expo Sci Environ Epidemiol 34, 115–125 (2024). https://doi.org/10.1038/s41370-023-00559-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41370-023-00559-5

Keywords

This article is cited by

Search

Advanced search

Quick links