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Determinants of urinary dialkyl phosphate metabolites in midlife women: the Study of Women’s Health Across the Nation Multi-Pollutant Study (SWAN-MPS)



Biomonitoring data and determinants of urinary dialkylphosphate (DAP) metabolites, markers of organophosphate pesticides, in racially diverse, non-occupationally exposed populations are scarce.


This study evaluated urinary concentrations and potential determinants of DAP metabolites of organophosphate pesticides in a multi-site, multi-racial/ethnic cohort of women aged 45–56 years, the Study of Women’s Health Across the Nation Multi-Pollutant Study (SWAN-MPS).


We analyzed 963 urine samples collected in 1999–2000, the baseline of SWAN-MPS for longitudinal studies, and quantified DAP metabolites, including dimethyl alkylphosphates (DMAPs): dimethylphosphate (DMP), dimethylthiophosphate (DMTP), dimethyldithiophosphate (DMDTP); and diethyl alkylphosphates (DEAPs): diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), using gas chromatography and triple quadrupole mass spectroscopy. Adjusted least squared geometric means (LSGMs) and 95% confidence intervals (CIs) were computed to compare DAP concentrations by socio-demographic, behavioral and dietary factors.


The geometric means (geometric standard deviations) of total DAPs, DMAPs, and DEAPs were 141 (2.63) nmol/L, 102 (2.99) nmol/L, and 26.8 (2.46) nmol/L, respectively. Body mass index (BMI) was inversely associated with DMAPs and DEAPs: LSGM (95% CI) = 68.8 (55.7–84.9) and 21.0 (17.7–25.0) nmol/L for women with obesity vs. 102 (84.7–123) and 30.1 (25.7–35.1) nmol/L for women with normal/underweight, respectively. Fruit consumption was positively (74.9 (62.1–90.2) for less than 5–6 servings/week vs. 105 (84.8–130) nmol/L for 1 serving/day and more) whereas meat consumption was inversely associated with DMAPs (110 (95.0–128) for seldom vs. 82.3 (59.5–114) nmol/L for often consumption). Fresh apple consumption appears to be attributed to the DMAP differences. Alcohol consumption was positively associated with DEAPs (27.5 (23.1–32.7) for 2 drinks/week and more vs. 23.0 (20.0–26.6) nmol/L for less than 1 drink/month). Black women had higher concentrations of DEAPs compared with White women (27.3 (21.2–35.2) vs. 23.2 (20.2–26.7) nmol/L).

Impact Statement

Organophosphate pesticides (OPs) are synthetic chemicals and currently the most widely used type of insecticides. We examined multi-site, multi-ethnic cohort of midlife women in the U.S. that offers a unique opportunity to evaluate major determinants of OP exposure. We improved OP metabolite detection rates and obtained accurate concentrations using an improved analytical technique. Our findings suggest that consumptions of fruit, meat and alcohol are important determinants of OP exposure for midlife women. Higher concentrations of diethyl OP metabolites in Black women compared to White women, even after accounting for dietary intake, suggests additional, but unknown racial-ethnic differences that affect exposure.

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Fig. 1: Spearman correlation coefficients for DAPs displayed using a heat map.
Fig. 2: Least squared geometric means of urinary DAP concentrations by site and race/ethnicity.

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Data availability

SWAN provides access to public use datasets that include data from SWAN screening, the baseline visit and follow-up visits ( To preserve participant confidentiality, some, but not all, of the data used for this manuscript are contained in the public use datasets. The corresponding author will on request detail the restrictions and any conditions under which access to some data may be provided. A link to the public use datasets is also located on the SWAN web site: Investigators who require assistance accessing the public use dataset may contact the SWAN Coordinating Center at the following email address:


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The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720). The study was also supported by the SWAN Repository (U01AG017719). This publication was supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. This study was also supported by grants from the National Institute of Environmental Health Sciences (NIEHS) R01-ES026578, R01-ES026964, R01-ES035087 and P30-ES017885, and by the Center for Disease Control and Prevention (CDC)/National Institute for Occupational Safety and Health (NIOSH) grant T42-OH008455. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. Clinical Centers: University of Michigan, Ann Arbor—Carrie Karvonen-Gutierrez, PI 2021 – present, Siobán Harlow, PI 2011–2021, MaryFran Sowers, PI 1994–2011; Massachusetts General Hospital, Boston, MA—Sherri‐Ann Burnett‐Bowie, PI 2020—Present; Joel Finkelstein, PI 1999–2020; Robert Neer, PI 1994–1999; Rush University, Rush University Medical Center, Chicago, IL—Imke Janssen, PI 2020—Present; Howard Kravitz, PI 2009–2020; Lynda Powell, PI 1994–2009; University of California, Davis/Kaiser—Elaine Waetjen and Monique Hedderson, PIs 2020—Present; Ellen Gold, PI 1994–2020; University of California, Los Angeles—Arun Karlamangla, PI 2020—Present; Gail Greendale, PI 1994–2020; Albert Einstein College of Medicine, Bronx, NY—Carol Derby, PI 2011—present, Rachel Wildman, PI 2010–2011; Nanette Santoro, PI 2004–2010; University of Medicine and Dentistry—New Jersey Medical School, Newark—Gerson Weiss, PI 1994–2004; and the University of Pittsburgh, Pittsburgh, PA – Rebecca Thurston, PI 2020—Present; Karen Matthews, PI 1994–2020. NIH Program Office: National Institute on Aging, Bethesda, MD—Rosaly Correa-de-Araujo 2020—present; Chhanda Dutta 2016–2020; Winifred Rossi 2012–2016; Sherry Sherman 1994–2012; Marcia Ory 1994–2001; National Institute of Nursing Research, Bethesda, MD—Program Officers. Central Laboratory: University of Michigan, Ann Arbor—Daniel McConnell (Central Ligand Assay Satellite Services). NIA Biorepository: Rosaly Correa-de-Araujo 2019—Present; SWAN Repository: University of Michigan, Ann Arbor—Siobán Harlow 2013–2018; Dan McConnell 2011–2013; MaryFran Sowers 2000–2011. Coordinating Center: University of Pittsburgh, Pittsburgh, PA—Maria Mori Brooks, PI 2012—present; Kim Sutton-Tyrrell, PI 2001–2012; New England Research Institutes, Watertown, MA—Sonja McKinlay, PI 1995–2001. Steering Committee: Susan Johnson, Current Chair. Chris Gallagher, Former Chair. We thank the study staff at each site and all the women who participated in SWAN. We also thank Drs. Habyeong Kang and Ning Ding for their help in data analysis.

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Sung-Hee Seo was responsible for the measurement of urinary DAPs, data analysis, interpretation of results, and writing—original draft, and revisions. Stuart Batterman oversaw DAPs method development and measurement analysis, laboratory administration, and contributed to results interpretation and manuscript revisions. Carrie Karvonen-Gutierrez contributed to funding acquisition, project administration, and manuscript revisions. Sung Kyun Park is the guarantor of this work and had full access to all the data in the study and takes responsibility for the contents of the manuscript. Sung Kyun Park was responsible for funding acquisition, study design protocols, oversight of statistical analysis, interpretation of results, project administration, and writing.

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Correspondence to Sung Kyun Park.

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Seo, SH., Batterman, S., Karvonen-Gutierrez, C.A. et al. Determinants of urinary dialkyl phosphate metabolites in midlife women: the Study of Women’s Health Across the Nation Multi-Pollutant Study (SWAN-MPS). J Expo Sci Environ Epidemiol (2024).

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