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Review Article

Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature

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Pages 151-175 | Received 06 Aug 2013, Accepted 24 Oct 2013, Published online: 14 Jan 2014

References

  • Adami HO, Berry SC, Breckenridge CB, et al. (2011). Toxicology and epidemiology: improving the science with a framework for combining toxicological and epidemiological evidence to establish causal inference. Toxicol Sci, 122, 223–34
  • Adibi JJ, Whyatt RM, Williams PL, et al. (2008). Characterization of phthalate exposure among pregnant women assessed by repeat air and urine samples. Environ Health Perspect, 116, 467–73
  • Andra SS, Makris KC. (2012). Thyroid disrupting chemicals in plastic additives and thyroid health. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev, 30, 107–51
  • ATSDR. (1995). Toxicological profile for diethylphthalate. Atlanta, GA: Agency for Toxic Substances and Disease Registry
  • ATSDR. (2002). Toxicological profile for di(2-ethylhexyl) phthalate. Atlanta, GA: Agency for Toxic Substances and Disease Registry
  • Aylward LL, Lorber M, Hays SM. (2011). Urinary DEHP metabolites and fasting time in NHANES. J Expo Sci Environ Epidemiol, 21, 615–24
  • Barr DB, Wilder LC, Caudill SP, et al. (2005). Urinary creatinine concentrations in the U.S. Population: implications for urinary biologic monitoring measurements. Environ Health Perspect, 113, 192–200
  • Bay K, Asklund C, Skakkebaek NE, Andersson AM. (2006). Testicular dysgenesis syndrome: possible role of endocrine disrupters. Best Pract Res Clin Endocrinol Metab, 20, 77–90
  • Berkowitz GS, Obel J, Deych E, et al. (2003). Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort. Environ Health Perspect, 111, 79–84
  • Berkowitz GS, Wetmur JG, Birman-Deych E, et al. (2004). In utero pesticide exposure, maternal paraoxonase activity, and head circumference. Environ Health Perspect, 112, 388–91
  • Blount BC, Silva MJ, Caudill SP, et al. (2000). Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect, 108, 979–82
  • Boas M, Feldt-Rasmussen U, Main KM. (2012). Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol, 355, 240–8
  • Boas M, Frederiksen H, Feldt-Rasmussen U, et al. (2010). Childhood exposure to phthalates: associations with thyroid function, insulin-like growth factor I, and growth. Environ Health Perspect, 118, 1458–64
  • Boo S, Froelicher ES. (2013). Secondary analysis of national survey datasets. Jpn J Nurs Sci, 10, 130–5
  • Braun JM, Smith KW, Williams PL, et al. (2012). Variability of urinary phthalate metabolite and bisphenol A concentrations before and during pregnancy. Environ Health Perspect, 120, 739–45
  • Casas L, Fernandez MF, Llop S, et al; INMA Project. (2011). Urinary concentrations of phthalates and phenols in a population of Spanish pregnant women and children. Environ Int, 37, 858–66
  • Caserta D, Mantovani A, Marci R, et al. (2011). Environment and women's reproductive health. Hum Reprod Update, 17, 418–33
  • Chellakooty M, Juul A, Boisen KA, et al. (2006). A prospective study of serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 in 942 healthy infants: associations with birth weight, gender, growth velocity, and breastfeeding. J Clin Endocrinol Metab, 91, 820–6
  • Curtin LR, Mohadjer LK, Dohrmann SM, et al. (2012). The National Health and Nutrition Examination Survey: sample design, 1999–2006. Vital Health Stat, 2, 1–39
  • Delaney A, Bagshaw SM, Ferland A, et al. (2007). The quality of reports of critical care meta-analyses in the Cochrane database of systematic reviews: an independent appraisal. Crit Care Med, 35, 589–94
  • Desvergne B, Feige1 JN, Casals-Casas C. (2009). PPAR-mediated activity of phthalates: a link to the obesity epidemic? Molecular Cellular Endocrinol, 304, 43–8
  • Dickersin K, Min YI. (1993). Publication bias: the problem that won't go away. Ann N Y Acad Sci, 703, 135–46; discussion 146–38
  • Durmaz E, Ozmert EN, Erkekoglu P, et al. (2010). Plasma phthalate levels in pubertal gynecomastia. Pediatrics, 125, e122–9
  • Duty SM, Calafat AM, Silva MJ, et al. (2005). Phthalate exposure and reproductive hormones in adult men. Hum Reprod, 20, 604–10
  • Dwan K, Altman DG, Arnaiz JA, et al. (2008). Systematic review of the empirical evidence of study publication bias and outcome reporting bias. PLoS One, 3, e3081
  • Easterbrook PJ, Berlin JA, Gopalan R, Matthews DR. (1991). Publication bias in clinical research. Lancet, 337, 867–72
  • Engel SM, Wolff MS. (2013). Causal inference considerations for endocrine disruptor research in children's health. Annu Rev Public Health, 34, 139–58
  • Eveillard A, Mselli-Lakhal L, Mogha A, et al. (2009). Di-(2-ethylhexyl)-phthalate (DEHP) activates the constitutive androstane receptor (CAR): a novel signalling pathway sensitive to phthalates. Biochem Pharmacol, 77, 1735–46
  • Feige JN, Gelman L, Rossi D, et al. (2007). The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J Biol Chem, 282, 19152–66
  • Fisman EZ, Tenembaum A. (2013). The metabolic syndrome entanglement: cutting the Gordian knot. Cardiol J [Epub ahead of print] (May 15). doi: 10.5603/CJ.a2013.0054
  • Frederiksen H, Skakkebaek NE, Andersson AM. (2007). Metabolism of phthalates in humans. Mol Nutr Food Res, 51, 899–11
  • Fromme H, Bolte G, Koch HM, et al. (2007). Occurrence and daily variation of phthalate metabolites in the urine of an adult population. Int J Hyg Environ Health, 210, 21–33
  • Geraghty SR, Khoury JC, Morrow AL, Lanphear BP. (2008). Reporting individual test results of environmental chemicals in breastmilk: potential for premature weaning. Breastfeed Med, 3, 207–13
  • Goldberg M, Silbergeld E. (2011). On multiple comparisons and on the design and interpretation of epidemiological studies of many associations. Environ Res, 111, 1007–9
  • Goodman M, Hays S. (2008). Asthma and swimming: a meta-analysis. J Asthma, 45, 639–47
  • Gordis L. (2008). Epidemiology. Philadelphia, PA: Saunders Elsevier
  • Grün F, Blumberg B. (2009). Minireview: the case for obesogens. Mol Endocrinol, 23, 1127–34
  • Grun F. (2010). Obesogens. Curr Opin Endocrinol Diabetes Obes, 17, 453–9
  • Hall GC, Sauer B, Bourke A, et al. (2012). Guidelines for good database selection and use in pharmacoepidemiology research. Pharmacoepidemiol Drug Saf, 21, 1–10
  • Hao C, Cheng X, Xia H, Ma X. (2012). The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice. Biosci Rep, 32, 619–29
  • Hao C, Cheng X, Guo J, et al. (2013). Perinatal exposure to diethyl-hexyl-phthalate induces obesity in mice. Front Biosci (Elite Ed), 5, 725–33
  • Hatch EE, Nelson JW, Qureshi MM, et al. (2008). Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environ Health, 7, 27
  • Hauser R, Calafat AM. (2005). Phthalates and human health. Occup Environ Med. 62, 806–18
  • Hauser R, Duty S, Godfrey-Bailey L, Calafat AM. (2004). Medications as a source of human exposure to phthalates. Environ Health Perspect, 112, 751–3
  • Hauser R, Sokol R. (2008). Science linking environmental contaminant exposures with fertility and reproductive health impacts in the adult male. Fertil Steril, 89, e59–65
  • Hennekens CH, DeMets D. (2011). Statistical association and causation: contributions of different types of evidence. JAMA, 305, 1134–5
  • Hiatt RA, Haslam SZ, Osuch J, Breast C, the Environment Research C. (2009). The breast cancer and the environment research centers: transdisciplinary research on the role of the environment in breast cancer etiology. Environ Health Perspect, 117, 1814–22
  • Hoppin JA, Brock JW, Davis BJ, Baird DD. (2002). Reproducibility of urinary phthalate metabolites in first morning urine samples. Environ Health Perspect, 110, 515–8
  • Huang PC, Kuo PL, Guo YL, et al. (2007). Associations between urinary phthalate monoesters and thyroid hormones in pregnant women. Hum Reprod, 22, 2715–22
  • IARC. (2000). Di(2-ethylhexyl) phthalate. IARC monographs on the evaluation of carcinogenic risks to humans/World Health Organization, International Agency for Research on Cancer, vol. 77, 41–148
  • IOM. (2012). Breast cancer and the environment: a life course approach. Washington, DC: Institute of Medicine of the National Academies
  • James-Todd T, Stahlhut R, Meeker JD, et al. (2012). Urinary phthalate metabolite concentrations and diabetes among women in the National Health and Nutrition Examination Survey (NHANES) 2001–2008. Environ Health Perspect, 120, 1307–13
  • Janesick A, Blumberg B. (2011). Minireview: PPARγ as the target of obesogens. J Steroid Biochem Mol Biol. 127, 4–8
  • Jurek AM, Maldonado G, Greenland S, Church TR. (2006). Exposure-measurement error is frequently ignored when interpreting epidemiologic study results. Eur J Epidemiol, 21, 871–6
  • Jurewicz J, Hanke W, Radwan M, Bonde JP. (2009). Environmental factors and semen quality. Int J Occup Med Environ Health, 22, 305–29
  • Kasper-Sonnenberg M, Koch HM, Wittsiepe J, Wilhelm M. (2012). Levels of phthalate metabolites in urine among mother–child-pairs – results from the Duisburg Birth Cohort study, Germany. Int J Hyg Environ Health, 215, 373–82
  • Kato K, Silva MJ, Reidy JA, et al. (2004). Mono(2-ethyl-5-hydroxyhexyl) phthalate and mono-(2-ethyl-5-oxohexyl) phthalate as biomarkers for human exposure assessment to di-(2-ethylhexyl) phthalate. Environ Health Perspect, 112, 327–30
  • Kornosky JL, Peck JD, Sweeney AM, et al. (2008). Reproductive characteristics of southeast Asian immigrants before and after migration. J Immigr Minor Health, 10, 135–43
  • Kotsopoulos J, Tworoger SS, Campos H, et al. (2010). Reproducibility of plasma and urine biomarkers among premenopausal and postmenopausal women from the Nurses' Health Studies. Cancer Epidemiol Biomarkers Prev, 19, 938–46
  • Kyzas PA, Denaxa-Kyza D, Ioannidis JP. (2007). Almost all articles on cancer prognostic markers report statistically significant results. European J Cancer, 43, 2559–79
  • LaKind JS, Goodman M, Mattison DR. Bisphenol A and indicators of obesity, glucose metabolism/type 2 diabetes and cardiovascular disease: a systematic review of epidemiologic research. Crit Rev Toxicol, in press
  • LaKind JS, Goodman M, Naiman DQ. (2012a). Use of NHANES data to link chemical exposures to chronic diseases: A cautionary tale. PloS One, 7, e51086
  • LaKind JS, Levesque J, Dumas P, et al. (2012b). Comparing United States and Canadian population exposures from National Biomonitoring Surveys: bisphenol A intake as a case study. J Expo Sci Environ Epidemiol, 22, 219–26
  • Lang IA, Galloway TS, Scarlett A, et al. (2008). Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA, 300, 1303–10
  • Lind L, Fors N, Hall J, et al. (2005). A comparison of three different methods to evaluate endothelium-dependent vasodilation in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Arterioscler Thromb Vasc Biol, 25, 2368–75
  • Lind PM, Lind L. (2011). Circulating levels of bisphenol A and phthalates are related to carotid atherosclerosis in the elderly. Atherosclerosis, 218, 207–13
  • Lind L, Lind PM. (2012). Can persistent organic pollutants and plastic-associated chemicals cause cardiovascular disease? J Intern Med, 271, 537–53
  • Lind PM, Roos V, Ronn M, et al. (2012a). Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women. Environ Health, 11, 21
  • Lind PM, Zethelius B, Lind L. (2012b). Circulating levels of phthalate metabolites are associated with prevalent diabetes in the elderly. Diabetes Care, 35, 1519–24
  • Lopez-Carrillo L, Hernandez-Ramirez RU, Calafat AM, et al. (2010). Exposure to phthalates and breast cancer risk in northern Mexico. Environ Health Perspect, 118, 539–44
  • Lord SJ, Gebski VJ, Keech AC. (2004). Multiple analyses in clinical trials: sound science or data dredging? Med J Aust, 181, 452–4
  • Main KM, Skakkebaek NE, Virtanen HE, Toppari J. (2010). Genital anomalies in boys and the environment. Best Pract Res Clin Endocrinol Metab, 24, 279–89
  • Manikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK. (2013). Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS One, 8, e55387
  • Marrone MT, Venkataramanan V, Goodman M, et al. (2013). Surgical interventions for drug-resistant tuberculosis: a systematic review and meta-analysis. Int J Tuberc Lung Dis, 17, 6–16
  • Meeker JD. (2010). Exposure to environmental endocrine disrupting compounds and men's health. Maturitas, 66, 236–41
  • Meeker JD, Calafat AM, Hauser R. (2012). Urinary phthalate metabolites and their biotransformation products: predictors and temporal variability among men and women. J Expo Sci Environ Epidemiol, 22, 376–85
  • Meeker JD, Ferguson KK. (2011). Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. Adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007–2008. Environ Health Perspect, 119, 1396–402
  • Melzer D, Rice NE, Lewis C, et al. (2010). Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 2003/06. PLoS One, 5:e8673
  • Mitani K, Izushi F, Kataoka H. (2004). Analysis of phthalate contamination in infusion solutions by automated on-line in-tube solid-phase microextraction coupled with high-performance liquid chromatography. J Anal Toxicol, 28, 575–80
  • Moher D, Cook DJ, Eastwood S, et al. (1999). Improving the quality of reports of meta-analyses of randomised controlled trials: the QUORUM Statement. Quality of reporting of meta-analyses. Lancet, 354, 1896–900
  • Moher D, Liberati A, Tetzlaff J, Altman DG. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol, 62, 1006–12
  • Olsén L, Lind L, Lind PM. (2012). Associations between circulating levels of bisphenol A and phthalate metabolites and coronary risk in the elderly. Ecotoxicol Environ Saf, 80, 179–83
  • Peck JD, Sweeney AM, Symanski E, et al. (2010). Intra- and inter-individual variability of urinary phthalate metabolite concentrations in Hmong women of reproductive age. J Expo Sci Environ Epidemiol, 20, 90–100
  • Perera FP, Rauh V, Tsai WY, et al. (2003). Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population. Environ Health Perspect, 111, 201–5
  • Potischman N, Weed DL. (1999). Causal criteria in nutritional epidemiology. Am J Clin Nutr, 69, 1309S-–14S
  • Ribas-Fito N, Ramon R, Ballester F, et al. (2006). Child health and the environment: the INMA Spanish study. Paediatr Perinat Epidemiol, 20, 403–10
  • Rothman KJ, Greenland S. (1998). Modern epidemiology. Philadelphia, PA: Lippincott Williams and Wilkins
  • Rothman KJ, Greenland S. (2005). Causation and causal inference in epidemiology. Am J Public Health, 95, S144–50
  • Rothman KJ. (1990). No adjustments are needed for multiple comparisons. Epidemiology, 1, 43–6
  • Saravanabhavan G, Guay M, Langlois E, et al. (2013). Biomonitoring of phthalate metabolites in the Canadian population through the Canadian Health Measures Survey (2007–2009). Int J Hyg Environ Health (Feb 15). doi: 10.1016/j.ijheh.2012.12.009
  • Schecter A, Lorber M, Guo Y, et al. (2013). Phthalate concentrations and dietary exposure from food purchased in New York State. Environ Health Perspect, 121, 473–94
  • Shankar A, Teppala S, Sabanayagam C. (2012). Bisphenol A and peripheral arterial disease: results from the NHANES. Environ Health Perspect, 120, 1297–300
  • Shea BJ, Grimshaw JM, Wells GA, et al. (2007). Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol, 7, 10
  • Shiue I. (2013). Urine phthalate concentrations are higher in people with stroke: United States National Health and Nutrition Examination Surveys (NHANES), 2001–2004. Eur J Neurol, 20, 728–31
  • Silva MJ, Barr DB, Reidy JA, et al. (2003). Glucuronidation patterns of common urinary and serum monoester phthalate metabolites. Arch Toxicol, 77, 561–7
  • Silva MJ, Barr DB, Reidy JA, et al. (2004). 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, 112, 331–8
  • Stahlhut RW, van Wijngaarden E, Dye TD, et al. (2007). Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect, 115, 876–82
  • Sullivan KM, Dean A, Soe MM. (2009). Openepi: a web-based epidemiologic and statistical calculator for public health. Public Health Rep, 124, 471–4
  • Sutton A, Abrams K, Jones D, et al. (1998). Systematic reviews of trials and other studies. Health Technol Assess, 2, 69–79
  • Svensson K, Hernandez-Ramirez RU, Burguete-Garcia A, et al. (2011). Phthalate exposure associated with self-reported diabetes among Mexican women. Environ Res, 111, 792–6
  • Tang-Péronard JL, Andersen HR, Jensen TK, Heitmann BL. (2011). Endocrine-disrupting chemicals and obesity development in humans: a review. Obes Rev, 12, 622–36
  • Teitelbaum SL, Britton JA, Calafat AM, et al. (2008). Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. Environ Res, 106, 257–69
  • Teitelbaum SL, Mervish N, Moshier EL, et al. (2012). Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environ Res, 112, 186–93
  • Thayer KA, Heindel JJ, Bucher JR, Gallo MA. (2012). Role of environmental chemicals in diabetes and obesity: a National Toxicology Program Workshop Review. Environ Health Perspect, 120, 779–789
  • Trasande L, Attina TM, Sathyanarayana S, et al. (2013a). Race/ethnicity-specific associations of urinary phthalates with childhood body mass in a nationally representative sample. Environ Health Perspect, 121, 501–6
  • Trasande L, Cronk C, Durkin M, et al. (2009). Environment and obesity in the national children's study. Environ Health Perspect, 117, 159–66
  • Trasande L, Sathyanarayana S, Spanier AJ, et al. (2013b). Urinary phthalates are associated with higher blood pressure in childhood. J Pediatr 132:e646--55
  • Vandenbroucke JP, von Elm E, Altman DG, et al. (2007). Strengthening the reporting of observational studies in epidemiology (strobe): explanation and elaboration. Epidemiology, 18, 805–35
  • Wang H, Zhou Y, Tang C, et al. (2013). Urinary phthalate metabolites are associated with body mass index and waist circumference in Chinese school children. PLoS One, 8, e56800
  • Wang HX, Zhou Y, Tang CX, et al. (2012). Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study. Environ Health, 11, 79
  • Whyatt RM, Adibi JJ, Calafat AM, et al. (2009). Prenatal di(2-ethylhexyl)phthalate exposure and length of gestation among an inner-city cohort. Pediatrics, 124, e1213–20
  • Wilhelm M, Wittsiepe J, Lemm F, et al. (2008). The Duisburg Birth Cohort study: influence of the prenatal exposure to PCDD/Fs and dioxin-like PCBs on thyroid hormone status in newborns and neurodevelopment of infants until the age of 24 months. Mutat Res, 659, 83–92
  • Wilson PW, D'Agostino RB, Levy D, et al. (1998). Prediction of coronary heart disease using risk factor categories. Circulation, 97, 1837–47
  • Wirth JJ, Rossano MG, Potter R, et al. (2008). A pilot study associating urinary concentrations of phthalate metabolites and semen quality. Syst Biol Reprod Med, 54, 143–54
  • Wittassek M, Wiesmüller GA, Koch HM, et al. (2007). Internal phthalate exposure over the last two decades – a retrospective human biomonitoring study. Int J Hyg Environ Health, 210, 319–33
  • Wolff MS, Engel SM, Berkowitz GS, et al. (2008). Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect, 116, 1092–7
  • Wolff MS, Teitelbaum SL, Pinney SM, et al. Breast Cancer and Environment Research Centers. (2010). Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates, and phenols and pubertal stages in girls. Environ Health Perspect, 118, 1039–46
  • Yolton K, Xu Y, Strauss D, et al. (2011). Prenatal exposure to bisphenol A and phthalates and infant neurobehavior. Neurotoxicol Teratol, 33, 558–66

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