CoChat
Sign Up
Cited by 436Effects and risks of endocrine disrupting chemicalsToxic Organic Pollutants ImpactPesticide Exposure and Toxicity

Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002

Open access
Hatch, Elizabeth E, Nelson, Jessica W, Qureshi, M Mustafa, Weinberg, Janice, Moore, Lynn L, Singer, Martha, Webster, Thomas F·2008·Environmental Health
DOI 10.1186/1476-069x-7-27PMC PMC2440739
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: Although diet and activity are key factors in the obesity epidemic, laboratory studies suggest that endocrine disrupting chemicals may also affect obesity. METHODS: We analyzed associations between six phthalate metabolites measured in urine and body mass index (BMI) and waist circumference (WC) in National Health and Nutrition Examination Survey (NHANES) participants aged 6-80. We included 4369 participants from NHANES 1999-2002, with data on mono-ethyl (MEP), mono-2-ethylhexyl (MEHP), mono-n-butyl (MBP), and mono-benzyl (MBzP) phthalate; 2286 also had data on mono-2-ethyl-5-hydroxyhexyl (MEHHP) and mono-2-ethyl-5-oxohexyl (MEOHP) phthalate (2001-2002). Using multiple regression, we computed mean BMI and WC within phthalate quartiles in eight age/gender specific models. RESULTS: The most consistent associations were in males aged 20-59; BMI and WC increased across quartiles of MBzP (adjusted mean BMI = 26.7, 27.2, 28.4, 29.0, p-trend = 0.0002), and positive associations were also found for MEOHP, MEHHP, MEP, and MBP. In females, BMI and WC increased with MEP quartile in adolescent girls (adjusted mean BMI = 22.9, 23.8, 24.1, 24.7, p-trend = 0.03), and a similar but less strong pattern was seen in 20-59 year olds. In contrast, MEHP was inversely related to BMI in adolescent girls (adjusted mean BMI = 25.4, 23.8, 23.4, 22.9, p-trend = 0.02) and females aged 20-59 (adjusted mean BMI = 29.9, 29.9, 27.9, 27.6, p-trend = 0.02). There were no important associations among children, but several inverse associations among 60-80 year olds. CONCLUSION: This exploratory, cross-sectional analysis revealed a number of interesting associations with different phthalate metabolites and obesity outcomes, including notable differences by gender and age subgroups. Effects of endocrine disruptors, such as phthalates, may depend upon endogenous hormone levels, which vary dramatically by age and gender. Individual phthalates also have different biologic and hormonal effects. Although our study has limitations, both of these factors could explain some of the variation in the observed associations. These preliminary data support the need for prospective studies in populations at risk for obesity.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1186/1476-069x-7-27

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • MEP, MEHP, MBzP, MEHHP, and MEOHP were associated with obesity in the US population.

    “MEP, MEHP, MBzP, MEHHP, and MEOHP were associated with obesity in the US population [198].”

    From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [198]

    The Results and Discussion report associations between the listed metabolites and BMI or waist circumference in NHANES participants. The claim overgeneralizes them to obesity in the US population: associations differed by age and sex, and MEHP was inversely associated with BMI in adolescent and adult females. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Several studies have shown a significant association between obesity and phthalate exposure.

    “Several studies have shown a significant association between obesity and phthalate exposure [193,196,198].”

    From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [198]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 46

  1. Hill JO Peters JC Environmental contributions to the obesity epidemic Science 1998 280 1371 1374 9603719 10.1126/science.280.5368.1371 · DOI
  2. Grun F Blumberg B Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling Endocrinology 2006 147 S50 55 16690801 10.1210/en.2005-1129 · DOI
  3. Heindel JJ Endocrine disruptors and the obesity epidemic Toxicol Sci 2003 76 247 249 14677558 10.1093/toxsci/kfg255 · DOI
  4. Mayes JS Watson GH Direct effects of sex steroid hormones on adipose tissues and obesity Obes Rev 2004 5 197 216 15458395 10.1111/j.1467-789X.2004.00152.x · DOI
  5. Hurst CH Waxman DJ Activation of PPARalpha and PPARgamma by environmental phthalate monoesters Toxicol Sci 2003 74 297 308 12805656 10.1093/toxsci/kfg145 · DOI
  6. Barak Y Kim S Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease PPAR Res 2007 2007 12781 17389768 PMC1791068
  7. Hauser R Calafat AM Phthalates and human health Occup Environ Med 2005 62 806 818 16234408 10.1136/oem.2004.017590 PMC1740925 · DOI · Paper page
  8. Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological profile for Di-n-butyl phthatlate (DBP) 2001 37931045
  9. Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological profile for Di (2-ethylhexyl) phthalate (DEHP) 2002 37040457
  10. Davis BJ Maronpot RR Heindel JJ Di-(2-ethylhexyl) phthalate suppresses estradiol and ovulation in cycling rats Toxicol Appl Pharmacol 1994 128 216 223 7940536 10.1006/taap.1994.1200 · DOI
  11. Gray LE Jr Ostby J Furr J Price M Veeramachaneni DN Parks L Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat Toxicol Sci 2000 58 350 365 11099647 10.1093/toxsci/58.2.350 · DOI · Paper page
  12. Main KM Mortensen GK Kaleva MM Boisen KA Damgaard IN Chellakooty M Schmidt IM Suomi AM Virtanen HE Petersen JH Anderssen AM Toppari J Skakkebaek NE Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age Environ Health Perspect 2006 114 270 276 16451866 PMC1367843
  13. Pan G Hanaoka T Yoshimura M Zhang S Wang P Tsukino H Inoue K Nakazawa H Tsugane S Takahashi K Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China Environ Health Perspect 2006 114 1643 1648 17107847 PMC1665432
  14. Swan SH Main KM Liu F Stewart SL Kruse RL Calafat AM Mao CS Redmon JB Ternand CL Sullivan S Teague JL Decrease in anogenital distance among male infants with prenatal phthalate exposure Environ Health Perspect 2005 113 1056 1061 16079079 PMC1280349
  15. Meeker JD Calafat AM Hauser R Di-(2-ethylhexyl) Phthalate Metabolites May Alter Thyroid Hormone Levels in Men Environ Health Perspect 2007 115 1029 1034 17637918 PMC1913587
  16. Stahlhut RW van Wijngaarden E Dye TD Cook S Swan SH Concentrations of Urinary Phthalate Metabolites are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males Environ Health Perspect 2007 115 876 882 17589594 PMC1892109
  17. Silva MJ Barr DB Reidy JA Malek NA Hodge CC Caudill SP Brock JW Needham LL Calafat AM Urinary levels of seven phthalate metabolites in the U.S. population from the National Health and Nutrition Examination Survey (NHANES) 1999–2000 Environ Health Perspect 2004 112 331 338 14998749 PMC1241863
  18. Barr DB Silva MJ Kato K Reidy JA Malek NA Hurtz D Sadowski M Needham LL Calafat AM Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers Environ Health Perspect 2003 111 1148 1151 12842765 PMC1241566
  19. Weuve J Sanchez BN Calafat AM Schettler T Green RA Hu H Hauser R Exposure to phthalates in neonatal intensive care unit infants: urinary concentrations of monoesters and oxidative metabolites Environ Health Perspect 2006 114 1424 1431 16966100 PMC1570064
  20. Janssen I Katzmarzyk PT Ross R Waist circumference and not body mass index explains obesity-related health risk Am J Clin Nutr 2004 79 379 384 14985210
  21. Barr DB Wilder LC Caudill SP Gonzalez AJ Needham LL Pirkle JL Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements Environ Health Perspect 2005 113 192 200 15687057 PMC1277864
  22. Koo JW Parham F Kohn MC Masten SA Brock JW Needham LL Portier CJ The association between biomarker-based exposure estimates for phthalates and demographic factors in a human reference population Environ Health Perspect 2002 110 405 410 11940459 PMC1240804
  23. Ogden CL Carroll MD Curtin LR McDowell MA Tabak CJ Flegal KM Prevalence of Overweight and Obesity in the United States, 1999–2004 JAMA 2006 295 1549 1555 16595758 10.1001/jama.295.13.1549 · DOI · Paper page
  24. Zhang Q Wang Y Socioeconomic inequality of obesity in the United States: do gender, age, and ethnicity matter? Social Science & Medicine 2004 58 1171 1180 14723911 10.1016/S0277-9536(03)00288-0 · DOI
  25. Hauser R Meeker JD Singh NP Silva MJ Ryan L Duty S Calafat AM DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites Hum Reprod 2007 22 688 695 17090632 10.1093/humrep/del428 · DOI
  26. Graubard BI Korn EL Analyzing health surveys for cancer-related objectives J Natl Cancer Inst 1999 91 1005 1016 10379963 10.1093/jnci/91.12.1005 · DOI
  27. Korn EL Graubard BI Epidemiologic studies utilizing surveys: accounting for the sampling design Am J Public Health 1991 81 1166 1173 1951829 PMC1405642
  28. Feige JN Gelman L Rossi D Zoete V Metivier R Tudor C Anghel SI Grosdidier A Lathion C Engelborghs Y Michielin O Wahli W Desvergne B The endocrine disruptor mono-ethyl-hexyl-phthalate is a selective PPARgamma modulator which promotes adipogenesis J Biol Chem 2007 282 19152 19166 17468099 10.1074/jbc.M702724200 · DOI
  29. Barber TM McCarthy MI Wass JAH Franks S Obesity and polycystic ovary syndrome Clinical Endocrinology 2006 65 137 145 16886951 10.1111/j.1365-2265.2006.02587.x · DOI
  30. Rolland-Cachera MF Deheeger M Maillot M Bellisle F Early adiposity rebound: causes and consequences for obesity in children and adults Int J Obes 30 S11 S17 10.1038/sj.ijo.0803514 17133230 · DOI
  31. Hauser R Duty S Godfrey-Bailey L Calafat AM Medications as a source of human exposure to phthalates Environ Health Perspect 2004 112 751 753 15121520 PMC1241971
  32. Kortenkamp A Ten Years of Mixing Cocktails – a Review of Combination Effects of Endocrine Disrupting Chemicals Environmental Health Perspectives 2007 115 98 105 18174957 PMC2174407
  33. Howdeshell KL Furr J Lambright CR Rider CV Wilson VS Gray LE Jr Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: altered fetal steroid hormones and genes Toxicol Sci 2007 99 190 202 17400582 10.1093/toxsci/kfm069 · DOI
  34. Fromme H Bolte G Koch HM Angerer J Boehmer S Drexler H Mayer R Liebl B Occurrence and daily variation of phthalate metabolites in the urine of an adult population Int J Hyg Environ Health 2007 210 21 33 17182278 10.1016/j.ijheh.2006.09.005 · DOI
  35. Hauser R Meeker JD Park S Silva MJ Calafat AM Temporal variability of urinary phthalate metabolite levels in men of reproductive age Environ Health Perspect 2004 112 1734 1740 15579421 PMC1253667
  36. Hoppin JA Brock JW Davis BJ Baird DD Reproducibility of urinary phthalate metabolites in first morning urine samples Environ Health Perspect 2002 110 515 518 12003755 PMC1240840
  37. Bility MT Thompson JT McKee RH David RM Butala JH Vanden Heuvel JP Peters JM Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters Toxicol Sci 2004 82 170 182 15310864 10.1093/toxsci/kfh253 · DOI
  38. Ishihara A Nishiyama N Sugiyama S Yamauchi K The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor Gen Comp Endocrinol 2003 134 36 43 13129501 10.1016/S0016-6480(03)00197-7 · DOI
  39. Sugiyama S Shimada N Miyoshi H Yamauchi K Detection of thyroid system-disrupting chemicals using in vitro and in vivo screening assays in Xenopus laevis Toxicol Sci 2005 88 367 374 16179385 10.1093/toxsci/kfi330 · DOI
  40. Breous E Wenzel A Loos U The promoter of the human sodium/iodide symporter responds to certain phthalate plasticisers Mol Cell Endocrinol 2005 244 75 78 16257484
  41. Shimada N Yamauchi K Characteristics of 3,5,3'-triiodothyronine (T3)-uptake system of tadpole red blood cells: effect of endocrine-disrupting chemicals on cellular T3 response J Endocrinol 2004 183 627 637 15590988 10.1677/joe.1.05893 · DOI
  42. Wenzel A Franz C Breous E Loos U Modulation of iodide uptake by dialkyl phthalate plasticisers in FRTL-5 rat thyroid follicular cells Mol Cell Endocrinol 2005 244 63 71 16289305 10.1016/j.mce.2005.02.008 · DOI
  43. Fisher JS Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome Reproduction 2004 127 305 315 15016950 10.1530/rep.1.00025 · DOI
  44. Gray LE Jr Wilson VS Stoker T Lambright C Furr J Noriega N Howdeshell K Ankley GT Guillette L Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals Int J Androl 2006 29 96 104 discussion 105–108. 16466529 10.1111/j.1365-2605.2005.00636.x · DOI
  45. Lampen A Zimnik S Nau H Teratogenic phthalate esters and metabolites activate the nuclear receptors PPARs and induce differentiation of F9 cells Toxicol Appl Pharmacol 2003 188 14 23 12668118 10.1016/S0041-008X(03)00014-0 · DOI
  46. Maloney EK Waxman DJ trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals Toxicol Appl Pharmacol 1999 161 209 218 10581215 10.1006/taap.1999.8809 · DOI

Cited by

Sorted by citations

Authors
Hatch, E. E., Nelson, J. W., Qureshi, M. M., Weinberg, J., Moore, L. L., Singer, M., & Webster, T. F.
Affiliations
Boston University (US)
Corresponding author
Hatch, Elizabeth E
ORCID
Venue
Environmental Health
Publisher
Springer Science and Business Media LLC
Published
2008-06-03
Volume
7
Issue
1
Pages
27-27
ISSN
1476-069X (ISSN-L)
DOI
10.1186/1476-069x-7-27
PMC
PMC2440739
OpenAlex
W2159145289
Cited by
436
References
4
Citations by year
2026: 6 · 2025: 13 · 2024: 29 · 2023: 14 · 2022: 27 · 2021: 32 · 2020: 31 · 2019: 29 · 2018: 29 · 2017: 36 · 2016: 30 · 2015: 33 · 2014: 33 · 2013: 23 · 2012: 32
FWCI
8.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Environmental Health (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • OpenBU (Boston University) (submittedVersion, cc-by)
Funders
National Institute of Environmental Health Sciences (R21ES013724)
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
Keywords
phthalate metabolites, urinary biomarkers, body mass index, waist circumference, obesity, endocrine disruptors, monoethyl phthalate, mono(2-ethylhexyl) phthalate, mono-n-butyl phthalate, monobenzyl phthalate, MEHHP, MEOHP, sex differences, age differences, NHANES, children and adolescents
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Child, Cross-Sectional Studies, Environmental Pollutants, Female, Humans, Male, Middle Aged, Nutrition Surveys, Obesity, Phthalic Acids, Plasticizers, United States, Body Mass Index, Adiposity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review