Urinary Concentrations of Bisphenol A and 4-Nonylphenol in a Human Reference Population
Open accessAbstract
Bisphenol A (BPA) is used to manufacture polycarbonate plastic and epoxy resins, which are used in baby bottles, as protective coatings on food containers, and for composites and sealants in dentistry. 4-Nonylphenol (NP) is used to make nonylphenol ethoxylates, nonionic surfactants applied as emulsifying, wetting, dispersing, or stabilizing agents in industrial, agricultural, and domestic consumer products. The potential for human exposure to BPA and NP is high because of their widespread use. We measured BPA and NP in archived urine samples from a reference population of 394 adults in the United States using isotope-dilution gas chromatography/mass spectrometry. The concentration ranges of BPA and NP were similar to those observed in other human populations. BPA was detected in 95% of the samples examined at concentrations ≥0.1 μg/L urine; the geometric mean and median concentrations were 1.33 μg/L (1.36 μg/g creatinine) and 1.28 μg/L (1.32 μg/g creatinine), respectively; the 95th percentile concentration was 5.18 μg/L (7.95 μg/g creatinine). NP was detected in 51% of the samples examined ≥0.1 μg/L. The median and 95th percentile concentrations were < 0.1 μg/L and 1.57 μg/L (1.39 μg/g creatinine), respectively. The frequent detection of BPA suggests widespread exposure to this compound in residents of the United States. The lower frequency of detection of NP than of BPA could be explained by a lower exposure of humans to NP, by different pharmacokinetic factors (i.e., absorption, distribution, metabolism, elimination), by the fact that 4-n-nonylphenol—the measured NP isomer—represents a small percentage of the NP used in commercial mixtures, or a combination of all of the above. Additional research is needed to determine the best urinary biomarker(s) to assess exposure to NP. Despite the sample population’s nonrepresentativeness of the U.S. population (although sample weights were used to improve the extent to which the results represent the U.S. population) and relatively small size, this study provides the first reference range of human internal dose levels of BPA and NP in a demographically diverse human population.
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Exposure to BPA is fairly ubiquitous, detected in urine in 90% of all humans sampled.
“Exposure to this chemical is fairly ubiquitous; as it has been detected in urine in 90% of all humans sampled [1].”
From Gestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice (2011) · cites this paper as [1]
The Results report detectable BPA in 95% of 394 urine samples and describe exposure as widespread. The claim gives 90% instead and extends the finding to “all humans sampled,” whereas the Discussion says this sample was relatively small and not representative of the U.S. population. (LLM, conf=0.90)
Experimental — accuracy not yet measuredDetectable levels of BPA have been found in human and animal fluids such as urine, blood, and breast milk.
“detectable levels of BPA have been found in fluids of human and animals, such as urine24, blood25 and breast milk26.”
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Cites
Exposure to bisphenol A advances puberty
Howdeshell, K. L., Hotchkiss, A. K., Thayer, K. A., Vandenbergh, J. G., & vom Saal, F. S. (1999) · Nature · doi:10.1038/44517 · Cited by 820 · see citing works
Flagged first, then by citations
Research works printed but not linked: 39
- Arakawa C Fujimaki K Yoshinaga J Imai H Serizawa S Shiraishi H 2004 Daily urinary excretion of bisphenol A Environ Health Prevent Med 9 22 26 PMC2723384 21432334
- Arenholt-Bindslev D Breinholt V Preiss A Schmalz G 1999 Time-related bisphenol-A content and estrogenic activity in saliva samples collected in relation to placement of fissure sealants Clin Oral Investig 3 120 125 10803122
- Coldham NG Sivapathasundaram S Dave M Ashfield LA Pottinger TG Goodall C 1998 Biotransformation, tissue distribution, and persistence of 4-nonylphenol residues in juvenile rainbow trout (Oncorhynchus mykiss) Drug Metabol Dispos 26 347 354 9531523
- Doerge DR Twaddle NC Churchwell MI Chang HC Newbold RR Delclos KB 2002 Mass spectrometric determination of p-nonylphenol metabolism and disposition following oral administration to Sprague-Dawley rats Reprod Toxicol 16 45 56 11934531
- Green T Swain C Van Miller JP Joiner RL 2003 Absorption, bioavailability, and metabolism of para-nonylphenol in the rat Regul Toxicol Pharmacol 38 43 51 12878053
- Guenther K Heinke V Thiele B Kleist E Prast H Raecker T 2002 Endocrine disrupting nonylphenols are ubiquitous in food Environ Sci Technol 36 1676 1680 11993862
- Hanaoka T Kawamura N Hara K Tsugane S 2002 Urinary bisphenol A and plasma hormone concentrations in male workers exposed to bisphenol A diglycidyl ether and mixed organic solvents Occup Environ Med 59 625 628 12205237 PMC1740362
- Hassold T Hunt P 2001 To ERR (meiotically) is human: the genesis of human aneuploidy Nat Rev Genet 2 280 291 11283700
- Hemmer MJ Hemmer BL Bowman CJ Kroll KJ Folmar LC Marcovich D 2001 Effects of p-nonylphenol, methoxychlor, and endosulfan on vitellogenin induction and expression in sheepshead minnow (Cyprinodon varie-gatus) Environ Toxicol Chem 20 336 343 11351433
- Howe SR Borodinsky L Lyon RS 1998 Potential exposure to bisphenol A from food contact use of epoxy coated cans J Coat Technol 70 69 74 9666897
- Hunt PA Koehler KE Susiarjo M Hodges CA Ilagan A Voigt RC 2003 Bisphenol A exposure causes meiotic aneuploidy in the female mouse Curr Biol 13 546 553 12676084
- Jackson S 1966 Creatinine in urine as an index of urinary excretion rate Health Phys 12 843 850 5963490
- Kawaguchi M Inoue K Sakui N Ito R Izumi S Makino T 2004 Stir bar sorptive extraction and thermal desorption-gas chromatography-mass spectrometry for the measurement of 4-nonylphenol and 4-tert-octylphenol in human biological samples J Chromatogr B Analyt Technol Biomed Life Sci 799 119 125 14659443
- Kim HS Shin JH Moon HJ Kang IH Kim TS Kim IY 2002 Comparative estrogenic effects of p-nonylphenol by 3-day uterotrophic assay and female pubertal onset assay Reprod Toxicol 16 259 268 12128099
- Kubo K Arai O Omura M Watanabe R Ogata R Aou S 2003 Low dose effects of bisphenol A on sexual differentiation of the brain and behavior in rats Neurosci Res 45 345 356 12631470
- Kuklenyik Z Ekong J Cutchins CD Needham LL Calafat AM 2003 Simultaneous measurement of urinary bisphenol A and alkylphenols by automated solid-phase extractive derivatization gas chromatography/mass spectrometry Anal Chem 75 6820 6825 14670041
- Kwack SJ Kwon O Kim HS Kim SS Kim SH Sohn KH 2002 Comparative evaluation of alkylphenolic compounds on estrogenic activity in vitro and in vivo J Toxicol Environ Health Part A 65 419 431 11936222
- Laws SC Carey SA Ferrell JM Bodman GJ Cooper RL 2000 Estrogenic activity of octylphenol, nonylphenol, bisphenol A and methoxychlor in rats Toxicol Sci 54 154 167 10746942
- Lynn HS 2001 Maximum likelihood inference for left-censored HIV RNA data Statist Med 20 33 45 11135346
- Maguire RJ 1999 Review of the persistence of nonylphenol and nonylphenol ethoxylates in aquatic environments Water Qual Res J Canada 34 37 78
- Markey CM Luque EH de Toro MM Sonnenschein C Soto AM 2001 In utero exposure to bisphenol A alters the development and tissue organization of the mouse mammary gland Biol Reprod 65 1215 1223 11566746
- Matsumoto A Kunugita N Kitagawa K Isse T Oyama T Foureman GL 2003 Bisphenol A levels in human urine Environ Health Perspect 111 101 104 12515686 PMC1241312
- Muller S Schmid P Schlatter C 1998 Pharmacokinetic behavior of 4-nonylphenol in humans Environ Toxicol Pharmacol 5 257 265 21781872
- Nagel SC vom Saal FS Thayer KA Dhar MG Boechler M Welshons WV 1997 Relative binding affinity serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol Environ Health Perspect 105 70 76 9074884 PMC1469837
- NCHS 1994 Plan and operation of the Third National Health and Nutrition Examination Survey, 1988–94 Vital Health Stat 1 32 1 407 7975354
- Ouchi K Watanabe S 2002 Measurement of bisphenol A in human urine using liquid chromatography with multi-channel coulometric electrochemical detection J Chromatogr B Analyt Technol Biomed Life Sci 780 365 370 12401363
- Peavy JV 1996. Surveys and sampling. In: Field Epidemiology (Gregg MB, ed). New York:Oxford University Press, 152–163.
- Pottenger LH Domoradzki JY Markham DA Hansen SC Cagen SZ Waechter JM 2000 The relative bioavailability and metabolism of bisphenol A in rats is dependent upon the route of administration Toxicol Sci 54 3 18 10746927
- Sajiki J Yonekubo J 2003 Leaching of bisphenol A (BPA) to sea-water from polycarbonate plastic and its degradation by reactive oxygen species Chemosphere 51 55 62 12586156
- Schonfelder G Wittfoht W Hopp H Talsness CE Paul M Chahoud I 2002 Parent bisphenol A accumulation in the human maternal–fetal–placental unit Environ Health Perspect 110 A703 A707 12417499 PMC1241091
- Staples CA Dorn PB Klecka GM O’Block ST Harris LR 1998 A review of the environmental fate, effects, and exposures of bisphenol A Chemosphere 36 2149 2173 9566294
- Thibaut R Debrauwer L Rao D Cravedi JP 1999 Urinary metabolites of 4-n-nonylphenol in rainbow trout (Oncorhynchus mykiss) Sci Tot Environ 233 193 200 10492905
- Volkel W Colnot T Csanady GA Filser JG Dekant W 2002 etabolism and kinetics of bisphenol A in humans at low doses following oral administration Chem Res Toxicol 15 1281 1287 12387626
- vom Saal FS Cooke PS Buchanan DL Palanza P Thayer KA Nagel SC 1998 A physiologically based approach to the study of bisphenol A and other estrogenic chemicals on the size of reproductive organs, daily sperm production, and behavior Toxicol Ind Health 14 239 260 9460178
- Welshons WV Nagel SC vom Saal FS 1998 The importance of protocol design and data reporting to research on endocrine disruption: response [Letter] Environ Health Perspect 106 A316 A317 PMC1533113 9734998
- White R Jobling S Hoare SA Sumpter JP Parker MG 1994 nvironmentally persistent alkylphenolic compounds are estrogenic Endocrinology 135 175 182 8013351
- Yang MH Kim SY Lee SM Chang SS Kawamoto T Jang JY 2003 Biological monitoring of bisphenol A in a Korean population Arch Environ Contam Toxicol 44 546 551 12712285
- Ying GG Williams B Kookana R 2002 Environmental fate of alkylphenols and alkylphenol ethoxylates. A review nviron Int 28 215 226 12222618
- Zalko D Costagliola R Dorio C Rathahao E Cravedi JP 2003 In vivo metabolic fate of the xeno-estrogen 4-n-nonylphenol in Wistar rats Drug Metabol Dispos 31 168 178 12527697
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Rochester, J. R. (2013) · Reproductive Toxicology · doi:10.1016/j.reprotox.2013.08.008 · Cited by 2,018 · see citing works
Exposure of the U.S. Population to Bisphenol A and 4- <i>tertiary</i> -Octylphenol: 2003–2004
Calafat, A. M., Ye, X., Wong, L.-Y., Reidy, J. A., & Needham, L. L. (2008) · Environmental Health Perspectives · doi:10.1289/ehp.10753 · Cited by 1,743 · see citing works
Self-citationDolinoy, D. C., Huang, D., & Jirtle, R. L. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703739104 · Cited by 1,369 · see citing works
Metabolism disrupting chemicals and metabolic disorders
Heindel, J. J., Blumberg, B., Cave, M., Machtinger, R., Mantovani, A., Mendez, M. A., Nadal, A., Palanza, P., Panzica, G., Sargis, R., et al. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.10.001 · Cited by 1,101 · see citing works
In vitro molecular mechanisms of bisphenol A action.
Wetherill, Y. B., Akingbemi, B. T., Kanno, J., McLachlan, J. A., Nadal, A., Sonnenschein, C., Watson, C. S., Zoeller, R. T., & Belcher, S. M. (2007) · Reproductive Toxicology · doi:10.1016/j.reprotox.2007.05.010 · Cited by 920 · see citing works
Greven, A.-C., Merk, T., Karagöz, F., Mohr, K., Klapper, M., Jovanović, B., & Palić, D. (2016) · Environmental Toxicology and Chemistry · doi:10.1002/etc.3501 · Cited by 357 · see citing works
The role of bisphenol A in shaping the brain, epigenome and behavior
Wolstenholme, J. T., Rissman, E. F., & Connelly, J. J. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.10.001 · Cited by 309 · see citing works
Environmental factors, epigenetics, and developmental origin of reproductive disorders
Ho, S.-M., Cheong, A., Adgent, M. A., Veevers, J., Suen, A. A., Tam, N. N. C., Leung, Y.-K., Jefferson, W. N., & Williams, C. J. (2017) · Reproductive Toxicology · doi:10.1016/j.reprotox.2016.07.011 · Cited by 226 · see citing works
Twenty-Four Hour Human Urine and Serum Profiles of Bisphenol A during High-Dietary Exposure
Teeguarden, J. G., Calafat, A. M., Ye, X., Doerge, D. R., Churchwell, M. I., Gunawan, R., & Graham, M. K. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr160 · Cited by 215 · see citing works
Self-citationGestational Exposure to Low Dose Bisphenol A Alters Social Behavior in Juvenile Mice
Wolstenholme, J. T., Taylor, J. A., Shetty, S. R. J., Edwards, M., Connelly, J. J., & Rissman, E. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025448 · Cited by 168 · see citing works
“Exposure to this chemical is fairly ubiquitous; as it has been detected in urine in 90% of all humans sampled [1].”
BackgroundUrinary bisphenol A and hypertension in a multiethnic sample of US adults
Shankar, A., & Teppala, S. (2012) · Journal of Environmental and Public Health · doi:10.1155/2012/481641 · Cited by 162 · see citing works
Epigenetic regulation of female puberty
Lomniczi, A., Wright, H., & Ojeda, S. R. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.08.003 · Cited by 136 · see citing works
Malaisé, Y., Menard, S., Cartier, C., Gaultier, E., Lasserre, F., Lencina, C., Harkat, C., Geoffre, N., Lakhal, L., Castan, I., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15196-w · Cited by 107 · see citing works
Adewale, H. B., Todd, K. L., Mickens, J. A., & Patisaul, H. B. (2011) · NeuroToxicology · doi:10.1016/j.neuro.2010.07.008 · Cited by 86 · see citing works
Liu, Z.-H., Ding, J.-J., Yang, Q.-Q., Song, H.-Z., Chen, X.-T., Xu, Y., Xiao, G.-R., & Wang, H.-L. (2016) · Scientific Reports · doi:10.1038/srep32492 · Cited by 53 · see citing works
- Authors
- Calafat, A. M., Kuklenyik, Z., Reidy, J. A., Caudill, S. P., Ekong, J., & Needham, L. L.
- Affiliations
- Centers for Disease Control and Prevention (US)
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2004-12-20
- Volume
- 113
- Issue
- 4
- Pages
- 391-395
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1278476
- OpenAlex
- W2037728383
- Cited by
- 1,031
- References
- 1
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 26 · 2023: 26 · 2022: 42 · 2021: 41 · 2020: 57 · 2019: 45 · 2018: 67 · 2017: 76 · 2016: 56 · 2015: 66 · 2014: 69 · 2013: 70 · 2012: 68
- FWCI
- 23.54
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Environmental Health Perspectives (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- 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
- bisphenol A, 4-nonylphenol, urinary biomarkers, human exposure, reference population, nonylphenol ethoxylates, nonionic surfactants, polycarbonate plastics, epoxy resin, creatinine-corrected concentrations, isotope dilution, exposure assessment, reference values, United States adults, biomonitoring, endocrine disruptors
- MeSH terms
- Bisphenol A Compounds, Adult, Benzhydryl Compounds, Environmental Monitoring, Environmental Pollutants, Female, Humans, Male, Middle Aged, Phenols, United States
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