Journal List > Ann Pediatr Endocrinol Metab > v.19(2) > 1516085317

Kim and Park: Phthalate exposure and childhood obesity

Abstract

Phthalates are commonly used as plasticizers and vehicles for cosmetic ingredients. Phthalate metabolites have documented biochemical activity including activating peroxisome proliferator-activated receptor and antiandrogenic effects, which may contribute to the development of obesity. In vitro and in vivo studies suggest that phthalates have significant effects on the development of obesity, especially after prenatal exposure at low doses. Although few studies have examined the effects of phthalate on obesity development in humans, some work has shown that phthalates affect humans and animals similarly. In this paper, we review the possible mechanisms of phthalate-induced obesity, and discuss evidence supporting the role of phthalates in the development of obesity in humans.

Introduction

Between the late 1970s and the early 2000s, the prevalence of obesity among Korean children and adolescents rapidly increased nearly 10 folds1). Although the rate of obesity has been leveled off, it remains prevalent particularly in boys2). In general, the increased prevalence of obesity is attributed to overeating, a sedentary life style, and genetic susceptibility. Although high-calorie fast foods and soft drinks are easily available, and people spend more time participating in sedentary activities, such as watching television or using a computer, these factors are insufficient to explain the huge increase in obesity during the 20th century3). In 2002, Baillei-Hamilton4) proposed that the global obesity epidemic was caused by exposure to endocrine disrupting chemicals (EDCs), and demonstrated that increased production of industrial chemicals coincided with increased obesity in the Unites States. A subset of EDCs that promote weight gain and obesity are referred to as "obesogens"5). Obesogens may cause obesity in several ways including disruption of critical lipid metabolism pathways to promote adipogenesis and fat storage, the alteration of the metabolic set point to induce positive energy balance, or increasing appetite5). Indeed, there is evidence showing a positive associations between obesogen levels, including phthalates, and body weight or body mass index (BMI) in children and adults.
Phthalates are diesters of 1,2-benzenedicaraboxylic acid (phthalic acid) and are used to increase the softness and flexibility of plastic products and as vehicles for fragrance in cosmetics. They are widely found in a variety of household products or personal care products, including building materials, shower curtains, children's toys, food packaging, and medical devices. Human exposure to phthalates can occur through ingestion of contaminated food and water, dermal contact, inhalation of polluted air, and parental exposure from medical devices6). Several in vivo and in vitro studies suggest that phthalates may promote obesity through antiandrogenic effects, antithyroid hormone activities, and/or activation of peroxisome proliferator-activated receptors (PPARs). Recently, human studies have been performed to study the association between phthalate exposure and obesity. Children are known to be more vulnerable to environmental exposure to phthalates, as compared to adults, because of their hand-to-mouth activity, larger surface area to weight ratio, and enhanced metabolic rate. As a result, there have been concerns that phthalates may promote childhood obesity in recent years.
In this paper, we review the possible mechanisms by which phthalate might influence the development of obesity, and discuss evidence from human studies suggesting an association between phthalate exposure and obesity-related biomarkers.

Diester phthalates and their potential sources of exposure

Phthalates have been used as plasticizers since the 1930s, and are currently used as additives in various consumer products (Table 1). The global consumption of phthalates is estimated to be several million tons per year7). High molecular weight (HMW) phthalates, such as di-2-ethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP) are used primarily in the manufacture of polyvinyl chloride (PVC) plastics for food packaging, building materials, and medical devices. Low molecular weight (LMW) phthalates, such as diethyl phthalate (DEP) and butylbenzyl phthalate (BBzP) are typically used in the manufacture of personal care products (e.g., perfumes, lotions, cosmetics, shampoo), paints, and adhesives. Phthalates are continuously emitted from PVC and plastic materials, resulting in contamination of indoor air, house dust, or food6,7). As a result, the primary methods of HMW phthalate exposure are ingestion of contaminated food or dust, or parental exposure. In contrast, the primary methods of LMW phthalate exposure are inhalation or dermal contact.

Metabolism of phthalates

Phthalates are rapidly metabolized and excreted in urine and feces after exposure. Fig. 1 demonstrates the metabolism of phthalates. In phase I hydrolysis, diester phthalates are hydrolyzed by esterases and lipases in the intestine and parenchyma to their respective monoester phthalates8). LMW phthalates are primarily excreted in urine and feces as a monoester, without further metabolism. In contrast, HMW phthalates are further metabolized from monoesters through hydroxylation or oxidation, to produce a number of oxidative metabolites. The oxidative metabolites of phthalates are excreted in urine within 24 hours of exposure. Alternatively, oxidative metabolites can undergo phase II conjugation to form hydrophilic glucuronide conjugates, which are excreted in urine rapidly8). Hydrolytic monoester phthalates can be measured in blood, urine, breast milk, and feces for use as the biomarkers of exposure to the corresponding phthalate diesters. Urinary phthalate metabolites are the most useful biomarkers, as they are relatively easy to collect and their levels in a single sample reflect the exposure to phthalates over several weeks or months9,10). The major biomarker of phthalates with short alkyl chains, such as di-n-butyl phthalate (DBP) and BBzP, are their monoesters in urine7). However, in the case of DEHP and DiNP, which are further metabolized from their primary monoesters and yield numerous oxidative metabolites, exposure must be estimated by taking the sum of primary and secondary metabolites in urine11). When daily phthalate intake was estimated in children using urinary phthalate biomarkers, DEHP was the most abundant phthalate, followed by DBP, di-iso-butyl phthalate, DEP and BBzP12).

Plausible mechanisms of phthalates effects on obesity

PPARs serve as metabolic sensors for various lipophilic hormones, fatty acids, and fatty acid metabolites, thereby controlling adipocyte proliferation and differentiation5). PPARα is highly expressed in liver, heart, skeletal muscle, gonads, and brown adipose tissue, where mediates peroxisome proliferation and stimulate fatty acid β-oxidation13,14,15). PPARα activators exert a variety of metabolic actions, depending on to the species, gender, dose, and timing of exposure. High doses DEHP protected adult mice from diet-induced obesity by promoting fatty acid oxidation and catabolic metabolism by activating PPARα16). In contrast, in mice expressing human PPARα, exposure to DEHP promoted fat accumulation and exacerbated obesity. Further, fetal exposure to low doses of mono(2-ethylhexyl) phthalate (MEHP) significantly increased the body weight of male offspring at postnatal day 60, whereas these effects were not evident in female offspring17). In rodents, phthalate monoesters, including MEHP and mono-n-butyl phthalate, are responsible for deformation of the male reproductive tract and dysfunction of both Leydig and Sertoli cells, resulting in decreased testosterone/androgen production and impaired spermatogenesis13,18). Importantly, phthalates do not interact with androgen receptors directly; rather their anti-androgenic effects are mediated through PPARα13,18). The antiandrogenic effects of phthalates have also been demonstrated in infants and adults19,20). As decreased androgen activity induces obesity, the anti-androgen effect through PPARα may be a possible mechanism of phthalate-induced obesity.
PPARγ is mainly expressed in adipose tissue, It plays a number of key roles including regulating the differentiation of adiopocytes and fat accumulation/storage in the adipose tissue. Additionally, PPARγ improves insulin sensitivity21). PPARγ agonists, such as thiazolidinediones, are potent insulin sensitizing agents used to control hyperglycemia in type 2 diabetes. However, their side effects include weight gain, which limits their usage in obese patients. Some phthalate monoesters, such as MEHP, mono-iso-nonyl phthalates, and mono-isodecyl phthalate act as PPARγ agonists, thereby promoting differentiation and lipid accumulation in 3T3-L1 cells, similar to thiazolidinediones22,23). Therefore, it is likely that phthalates exert an adipogenic effect though the activation of PPARγ. However, few in vivo animal studies have been performed to assess the effects of phthalate on PPARγ and adipogenesis17).
Another possible mechanism by which phthalates might promote obesity is through the disruption of thyroid function, which plays a key role in the regulation of energy balance and metabolism. There is some evidence that thyroid function plays a role in the regulation of BMI, as small changes in thyroid-stimulating hormone (TSH) or thyroxine levels within the normal range can cause measurable differences in resting energy expenditure in chronic hypothyroidism patients, and slight elevation of serum TSH levels are associated with both weight gain over 5 years and obesity in a population study24,25). In rodent studies, exposure to DEHP lowered plasma thyroxine and decreased iodide uptake of thyroid follicular cells26,27). Recent human studies have also demonstrated possible effects of phthalate exposure on thyroid function in children and adults28,29,30,31).
Finally, the "thrifty phenotype" resulting from exposure to undernourished fetal environment and EDCs could be one of plausible mechanisms by which phthalates promote obesity32). Epigenetic changes, induced by a suboptimal fetal environment, may result in increased uptake and conservation of nutrients, and predispose individuals to obesity and other metabolic disorders32). Epidemiological studies provide evidence that maternal malnutrition during pregnancy and subsequent low birth weight is associated with obesity later in life33,34,35). In rodent studies, maternal exposure to DBP or DEHP during the gestational period have been reported to decrease birth weight in offsprings36,37). Studies regarding of the effect of phthalate exposure on preterm delivery and/or fetal growth in humans are limited and conflicting. Some studies suggested that there is a positive association between fetal phthalate exposure and premature delivery or lower birth weight38,39,40), but other studies failed to show a significant relationship41,42). Prospective investigations are needed to reveal the validity of the hypothesis that phthalate exposure results in low birth weight and subsequent obesity.

Phthalate exposure and obesity development in human

Table 2 presents the results of human studies investigating the effects of phthalate exposure on obesity. Most epidemiologic studies examining the association between phthalate exposure and obesity have been based on the data from the National Health and Nutrition Examination Survey (NHANES)43,44,45,46). Regarding adulthood obesity, Stahlhut et al.43) demonstrated a positive association between urinary monoethyl phthalate (MEP), monobenzyl phthalate, mono(2-ethyl-5-hydroxylhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate and waist circumference (WC) in male adults, using data from NHANES 1999-200243). Using the same data, Hatch et al.44) showed a positive association between urinary MEP and both BMI and WC in female adults. Recently, a study from NHANES 2007-2010 found that HMW phthalates were associated with an increased risk of obesity in male adults, while DEHP phthalates were associated with increased obesity in females46). A prospective study from Sweden investigated serum phthalate metabolites in elderly subjects (70 years), and measured their body composition by dual-energy X-ray absorptiometry (DXA) two years later. In this study, serum mono-isobutyl phthalate levels were significantly correlated with increased BMI, WC, total fat mass and trunk fat mass by DXA in females, but not in males47).
Emerging evidence suggest childhood exposure to some phthalates also may increase the risk of obesity. In a study of Hatch et al.44), BMI and WC increased with urinary MEP concentrations among female girls in the United States. Two recent studies using data from NHANES found that urinary levels of LMW phthalates were associated with higher odds for obesity in children and adolescents45,46). A prospective cohort study also found that urinary LMW phthalate metabolite concentrations were positively associated with BMI in overweight children. However, no associations were reported among all the total subjects or normal weight subjects alone48). The health effects of phthalate exposure appear to be complex, as they are dependent on several factors, such as the time of exposure, level of exposure, type of phthalates, and other environmental/genetic factors of the individuals.

Conclusions

Many in vitro studies indicate that phthalates are likely obesogens, promoting obesity via several mechanisms, including activation of PPARs, antithyroid effects, and epigenetic modulation. The fetal period appears to be a critical window for exposure, and differential effects are observed depending on the dose of phthalates received and gender. Recent human studies have examined the possible effects of phthalate exposure on the development of obesity, although most of them are cross-sectional and short-term prospective studies. Although the random concentrations of phthalate metabolites have good reproducibility, large-scaled longitudinal study including measures at different life ages is needed to establish the impact of phthalate exposure on the obesity epidemic.

Acknowledgments

This work was supported by grant 11162KFDA701 from the Korea Food & Drug Administration in 2011.

Notes

No potential conflict of interest relevant to this article was reported.

References

1. Park YS, Lee DH, Choi JM, Kang YJ, Kim CH. Trend of obesity in school age children in Seoul over the past 23 years. Korean J Pediatr. 2004; 47:247–257.
2. Kim KE, Kim SH, Park S, Khang YH, Park MJ. Changes in prevalence of obesity and underweight among Korean children and adolescents: 1998-2008. Korean J Obes. 2012; 21:228–235.
crossref
3. Morris JN. Obesity in Britain: lifestyle data do not support sloth hypothesis. BMJ. 1995; 311:1568–1569. PMID: 8520410.
4. Baillie-Hamilton PF. Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med. 2002; 8:185–192. PMID: 12006126.
crossref
5. Hauser R, Calafat AM. Phthalates and human health. Occup Environ Med. 2005; 62:806–818. PMID: 16234408.
crossref
6. Wormuth M, Scheringer M, Vollenweider M, Hungerbuhler K. What are the sources of exposure to eight frequently used phthalic acid esters in Europeans? Risk Anal. 2006; 26:803–824. PMID: 16834635.
crossref
7. Calafat AM, McKee RH. Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study. Environ Health Perspect. 2006; 114:1783–1789. PMID: 17107868.
crossref
8. 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. PMID: 15579421.
crossref
9. Teitelbaum SL, Britton JA, Calafat AM, Ye X, Silva MJ, Reidy JA, et al. Temporal variability in urinary concentrations of phthalate metabolites, phytoestrogens and phenols among minority children in the United States. Environ Res. 2008; 106:257–269. PMID: 17976571.
crossref
10. Wittassek M, Angerer J. Phthalates: metabolism and exposure. Int J Androl. 2008; 31:131–138. PMID: 18070048.
crossref
11. Bekö G, Weschler CJ, Langer S, Callesen M, Toftum J, Clausen G. Children's phthalate intakes and resultant cumulative exposures estimated from urine compared with estimates from dust ingestion, inhalation and dermal absorption in their homes and daycare centers. PLoS One. 2013; 8:e62442. PMID: 23626820.
12. Grün F, Blumberg B. Endocrine disrupters as obesogens. Mol Cell Endocrinol. 2009; 304:19–29. PMID: 19433244.
crossref
13. Corton JC, Lapinskas PJ. Peroxisome proliferator-activated receptors: mediators of phthalate ester-induced effects in the male reproductive tract? Toxicol Sci. 2005; 83:4–17. PMID: 15496498.
crossref
14. Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications--a review. Nutr J. 2014; 13:17. PMID: 24524207.
15. Larsen TM, Toubro S, Astrup A. PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disord. 2003; 27:147–161. PMID: 12586994.
crossref
16. Feige JN, Gerber A, Casals-Casas C, Yang Q, Winkler C, Bedu E, et al. The pollutant diethylhexyl phthalate regulates hepatic energy metabolism via species-specific PPARalpha-dependent mechanisms. Environ Health Perspect. 2010; 118:234–241. PMID: 20123618.
crossref
17. Hao C, Cheng X, Xia H, Ma X. The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice. Biosci Rep. 2012; 32:619–629. PMID: 22953781.
crossref
18. Foster PM, Mylchreest E, Gaido KW, Sar M. Effects of phthalate esters on the developing reproductive tract of male rats. Hum Reprod Update. 2001; 7:231–235. PMID: 11392369.
crossref
19. Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, et al. 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. PMID: 16451866.
crossref
20. Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, Tsukino H, et al. 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. PMID: 17107847.
crossref
21. Lehrke M, Lazar MA. The many faces of PPARgamma. Cell. 2005; 123:993–999. PMID: 16360030.
22. Hurst CH, Waxman DJ. Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci. 2003; 74:297–308. PMID: 12805656.
23. Bility MT, Thompson JT, McKee RH, David RM, Butala JH, Vanden Heuvel JP, et al. Activation of mouse and human peroxisome proliferator-activated receptors (PPARs) by phthalate monoesters. Toxicol Sci. 2004; 82:170–182. PMID: 15310864.
crossref
24. al-Adsani H, Hoffer LJ, Silva JE. Resting energy expenditure is sensitive to small dose changes in patients on chronic thyroid hormone replacement. J Clin Endocrinol Metab. 1997; 82:1118–1125. PMID: 9100583.
25. Knudsen N, Laurberg P, Rasmussen LB, Bulow I, Perrild H, Ovesen L, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005; 90:4019–4024. PMID: 15870128.
crossref
26. Erkekoglu P, Giray BK, Kizilgun M, Hininger-Favier I, Rachidi W, Roussel AM, et al. Thyroidal effects of di-(2-ethylhexyl) phthalate in rats of different selenium status. J Environ Pathol Toxicol Oncol. 2012; 31:143–153. PMID: 23216639.
crossref
27. 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. PMID: 16289305.
crossref
28. 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. PMID: 17637918.
crossref
29. Meeker JD, Ferguson KK. 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. 2011; 119:1396–1402. PMID: 21749963.
crossref
30. Boas M, Frederiksen H, Feldt-Rasmussen U, Skakkebæk NE, Hegedus L, Hilsted L, et al. Childhood exposure to phthalates: associations with thyroid function, insulin-like growth factor I, and growth. Environ Health Perspect. 2010; 118:1458–1464. PMID: 20621847.
crossref
31. Wu MT, Wu CF, Chen BH, Chen EK, Chen YL, Shiea J, et al. Intake of phthalate-tainted foods alters thyroid functions in Taiwanese children. PLoS One. 2013; 8:e55005. PMID: 23383031.
crossref
32. Janesick A, Blumberg B. Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res C Embryo Today. 2011; 93:34–50. PMID: 21425440.
crossref
33. Ravelli GP, Stein ZA, Susser MW. Obesity in young men after famine exposure in utero and early infancy. N Engl J Med. 1976; 295:349–353. PMID: 934222.
crossref
34. Martorell R, Stein AD, Schroeder DG. Early nutrition and later adiposity. J Nutr. 2001; 131:874S–880S. PMID: 11238778.
crossref
35. Ong KK, Loos RJ. Rapid infancy weight gain and subsequent obesity: systematic reviews and hopeful suggestions. Acta Paediatr. 2006; 95:904–908. PMID: 16882560.
crossref
36. Lamb JC 4th, Chapin RE, Teague J, Lawton AD, Reel JR. Reproductive effects of four phthalic acid esters in the mouse. Toxicol Appl Pharmacol. 1987; 88:255–269. PMID: 3564043.
crossref
37. Jarfelt K, Dalgaard M, Hass U, Borch J, Jacobsen H, Ladefoged O. Antiandrogenic effects in male rats perinatally exposed to a mixture of di(2-ethylhexyl) phthalate and di(2-ethylhexyl) adipate. Reprod Toxicol. 2005; 19:505–515. PMID: 15749265.
crossref
38. Meeker JD, Hu H, Cantonwine DE, Lamadrid-Figueroa H, Calafat AM, Ettinger AS, et al. Urinary phthalate metabolites in relation to preterm birth in Mexico city. Environ Health Perspect. 2009; 117:1587–1592. PMID: 20019910.
crossref
39. Zhang Y, Lin L, Cao Y, Chen B, Zheng L, Ge RS. Phthalate levels and low birth weight: a nested case-control study of Chinese newborns. J Pediatr. 2009; 155:500–504. PMID: 19555962.
crossref
40. Huang Y, Li J, Garcia JM, Lin H, Wang Y, Yan P, et al. Phthalate levels in cord blood are associated with preterm delivery and fetal growth parameters in Chinese women. PLoS One. 2014; 9:e87430. PMID: 24503621.
crossref
41. Wolff MS, Engel SM, Berkowitz GS, Ye X, Silva MJ, Zhu C, et al. Prenatal phenol and phthalate exposures and birth outcomes. Environ Health Perspect. 2008; 116:1092–1097. PMID: 18709157.
crossref
42. Suzuki Y, Niwa M, Yoshinaga J, Mizumoto Y, Serizawa S, Shiraishi H. Prenatal exposure to phthalate esters and PAHs and birth outcomes. Environ Int. 2010; 36:699–704. PMID: 20605637.
crossref
43. 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. PMID: 17589594.
crossref
44. Hatch EE, Nelson JW, Qureshi MM, Weinberg J, Moore LL, Singer M, et al. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999-2002. Environ Health. 2008; 7:27. PMID: 18522739.
crossref
45. Trasande L, Attina TM, Sathyanarayana S, Spanier AJ, Blustein J. Race/ethnicity-specific associations of urinary phthalates with childhood body mass in a nationally representative sample. Environ Health Perspect. 2013; 121:501–506. PMID: 23428635.
crossref
46. Buser MC, Murray HE, Scinicariello F. Age and sex differences in childhood and adulthood obesity association with phthalates: Analyses of NHANES 2007-2010. Int J Hyg Environ Health. 2014; 3. 05. [Epub]. http://dx.doi.org/10.1016/j.ijheh.2014.02.005.
crossref
47. Lind PM, Roos V, Ronn M, Johansson L, Ahlstrom H, Kullberg J, et al. Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women. Environ Health. 2012; 11:21. PMID: 22472124.
crossref
48. Teitelbaum SL, Mervish N, Moshier EL, Vangeepuram N, Galvez MP, Calafat AM, et al. Associations between phthalate metabolite urinary concentrations and body size measures in New York City children. Environ Res. 2012; 112:186–193. PMID: 22222007.
crossref
Fig. 1
Metabolic pathways of phthalates.
apem-19-69-g001
Table 1.
Diester phthalates and their potential sources of exposure
Phthalate (Abbreviation) Sources of exposure Metabolites
Low molecular weight
 Dimethyl phthalate (DMP) Personal care products (deodorant, fragrance atershaves, shampoos, hair styling) Monomethyl phthalate (MMP)
 Dietyl phthalate (DEP) Personal care products (deodorant, fragrance aftershaves, shampoos, hair styling, skin care, nail care, makeup, baby preperations) Monoethyl phthalate (MEP)
 Di-n-butyl phthalate (DBP) Paints, adhesives, Personal care products (perfumes, aftershaves, nail care, makeup) Mono-n-butyl phthalate (MBP)
 Di-iso-butyl phthalate (DiBP) Paints, adhesives Mono-iso-butyl phthalate (MiBP)
High molecular weight
 Butylbenzyl phthalate (BBzP) Paint, adhesives, car care products, toys, food packaging, synthetic leather, deodorants, Monobenzyl phthalate (MBzP)
 Di (2-ethylhexyl) phthalate (DEHP) Household products (toys, floor tiles, wall coverings, furniture, paints, adhesives, gloves), dust, food packaging, medical devices Mono(2-ethylhexyl) phthalate (MEHP)
Mono(2-ethyl-5-hydroxylhexyl) phthalate (MEHHP)
Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP)
Mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)
Mono(2-carboxy-hexyl) phthalate (MCHP)
 Di-iso-nonyl phthalate (DiNP) Household products (toys, floor tiles, wall coverings, furniture, paints, adhesives, gloves), clothes and footwear, car interiors, food packaging, medical devices Mono-iso-nonyl phthalates (MiNP)
Mono(hydroxy-iso-nonyl) phthalate (MHiNP)
Mono(oxo-iso-nonyl) phthalate (MOiNP)
Mono(carboxy-iso-octyl) phthalate (MCiOP)
 Di-n-octyl phthalate (DnOP) Household products (floorings, carpet tiles, vinyl gloves, garden hoses, wire and cable insulation, adhesives), food applications (package sealants, bottle cap liners) Mono-(3-carboxypropyl) phthalate (MCPP)
Mono-n-octyl phthalate (MOP)
 Di-isodecyl phthalate (DiDP) Household products (toys, coated fabrics, vinyl flooring, wall coverings, lamination film, wire and cable insulation, foot wear, paints, adhesives), school supplies (scented erasers and pencil case) Mono-isodecyl phthalate (MiDP)
Mono-(carboxynonyl) phthalate (MCNP)
Table 2.
Human studies on phthalate exposure and obesity development
Study population Exposure assessment Findings Reference
US, male participants from NHANES 1999-2002 aged >18 yr (n=1,443) Cross-sectional study Positive association between WC and MEP, MBzP, MEHHP, MEOHP Stahlhut et al. [43]
Urine – 6 phthalates (MBP, MEP, MEHP, MBzP, MEHHP, MEOHP)
US, participants from NHANES 1999-2002 aged 6-80 yr (n=6,369) Cross-sectional study Positive association between BMI/WC and MEP, MBzP, MBP, MEHHP, MEOHP in males aged 20–59 yr Hatch et al. [44]
Urine – 6 phthalates (MBP, MEP, MEHP, MBzP, MEHHP, MEOHP) Rositive association between BMI/WC and MER in females aged 12-59 yr
Negative association between BMI and MEHR in females aged 12-59 yr
US, participants from NHANES 2007-2010 aged > 6 yr Cross-sectional study Rositive association between obesity risk and LMW metabolites in males aged 6-19 yr Buser et al. [46]
Urine – 10 phthalates Rositive associations between obesity risk and HMW metabolites in males aged > 20 yr
LMW phthalates (MBP, MEP, MiBP), HMW phthalates (MECPP, MEHHP, MEOHP, MEHP, MBzP, MCNP, MCOP) Rositive associations between obesity risk and DEHR metabolites in females aged > 20 yr
Sweden, elderly aged 70 yr (n=1,016) Prospective study Rositive association between MER and WC/fat mass obtained 2 yr later among females Lind et al. [47]
Blood– 4 phthalates
MEP, MEHP, MiBP, MMP
US, participants from NHANES 2003-2008 aged 6-19 yr (n=2,884) Cross-sectional study Rositive association between obesity risk and sum of molar concentrations LMW phthalates among non-Hispanic blacks Trasande et al. [45]
Urine – 9 phthalates
LMW phthalates (MBP, MEP, MiBP), HMW phthalates (MECPP, MCPP, MEHHP, MEOHP, MEHP, MBzP)
New York, children aged 6-8 yr Hispanic and Black Prospective study Rositive association between LMW phthalates and BMI/WC obtained 1 yr later among overweight children Teitelbaum et al. [48]
Urine – 9 phthalates
LMW phthalates (MBP, MEP, MiBP), HMW phthalates (MECPP, MCPP, MEHHP, MEOHP, MEHP, MBzP) No associations among normal weight subjects

NHANES, National Health and Nutrition Examination Survey; MBP, mono-n-butyl phthalate; MEP, monoethyl phthalate; MEHP, mono(2-ethylhexyl) phthalate; MBzP, monobenzyl phthalate; MEHHP, mono(2-ethyl-5-hydroxylhexyl) phthalate; MEOHP, mono(2-ethyl-5-oxohexyl) phthalate; WC, waist circumference; BMI, body mass index; LMW, low molecular weight; MiBP, mono-iso-butyl phthalate; MECPP, mono(2-ethyl-5-carboxypentyl) phthalate; MCNP, mono-(carboxynonyl) phthalate; MCOP, mono(carboxyoctyl) phthalate; DEHP, di(2-ethylhexyl) phthalate ; MMP, monomethyl phthalate; HMW, high molecular weight; MCPP, mono(3carboxypropyl) phthalate.

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