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A systematic review on the adverse health effects of di-2-ethylhexyl phthalate

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Abstract

Di (ethylhexyl) phthalate (DEHP) is a global environmental pollutant. This study aims to systematically review the literature on health effects of exposure to DEHP including effects on reproductive health, carcinogenesis, pregnancy outcome, and respiratory system. The literature search was done through Scopus, ISI Web of Science, Google Scholar, PubMed, Medline, and the reference lists of previous review articles to identify relevant articles published to June 2016 in each subject area. The inclusion criteria were as follows: original research, cross-sectional studies, case–control studies, cohort studies, interventional studies, and review articles. Both human and animal studies were included. The search was limited to English language papers. Conference papers, editorials, and letters were not included. The systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Overall, 152 of the 407 papers met the inclusion criteria. We provided an up-to-date comprehensive and critical assessment of both human and animal studies undertaken to explore the effects of DEHP. It revealed that in experimental studies, exposure to DEHP mainly targeted the reproductive, neurodevelopment, and respiratory systems. Human studies reported that exposure to this contaminant had carcinogenic effects and influenced neurodevelopment in early life. This systematic review underscored the adverse health effects of DEHP for pregnant women and the pediatric age group. It summarizes different response of humans and experimental animals to DEHP exposure, and some suggested underlying mechanisms.

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References

  • Adibi JJ, Perera FP, Jedrychowski W, Camann DE, Barr D, Jacek R, Whyatt RM (2003) Prenatal exposures to phthalates among women in New York and Krakow, Poland. Environ Health Perspect 111:1719–1722

    Article  CAS  Google Scholar 

  • Agarwal DK, Lawrence WH, Autian J (1985) Antifertility and mutagenic effects in mice from parenteral administration of di-2-ethylhexyl phthalate (DEHP. J Toxicol Environ Health 16:71–84. doi:10.1080/15287398509530720

    Article  CAS  Google Scholar 

  • Agarwal DK, Eustis S, Lamb JC, Reel JR, Kluwe WM (1986) Effects of di(2-ethylhexyl) phthalate on the gonadal pathophysiology, sperm morphology, and reproductive performance of male rats. Environ Health Perspect 65:343–350

    CAS  Google Scholar 

  • Agarwal DK, Lawrence WH, Turner JE, Autian J (1989) Effects of parenteral di-(2-ethylhexyl) phthalate (DEHP) on gonadal biochemistry, pathology, and reproductive performance of mice. J Toxicol Environ Health 26:39–59. doi:10.1080/15287398909531232

    Article  CAS  Google Scholar 

  • Ait Bamai Y et al. (2014) Exposure to house dust phthalates in relation to asthma and allergies in both children and adults. Sci Total Environ 485-486:153–163. doi:10.1016/j.scitotenv.2014.03.059

    Article  CAS  Google Scholar 

  • Akingbemi BT et al. (2001) Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl) phthalate. Biol Reprod 65:1252–1259

    Article  CAS  Google Scholar 

  • Akingbemi BT, Ge R, Klinefelter GR, Zirkin BR, Hardy MP (2004) Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc Natl Acad Sci U S A 101:775–780

    Article  CAS  Google Scholar 

  • Albert O, Jegou B (2014) A critical assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood. Hum Reprod Update 20:231–249. doi:10.1093/humupd/dmt050

    Article  CAS  Google Scholar 

  • Ambruosi B et al. (2011) In vitro acute exposure to DEHP affects oocyte meiotic maturation, energy and oxidative stress parameters in a large animal model. PLoS One 6:e27452. doi:10.1371/journal.pone.0027452

    Article  CAS  Google Scholar 

  • Andrade AJ et al. (2006) A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats. Toxicology 228:85–97. doi:10.1016/j.tox.2006.08.020

    Article  CAS  Google Scholar 

  • Arbuckle TE et al. (2014) Phthalate and bisphenol A exposure among pregnant women in Canada—results from the MIREC study. Environ Int 68:55–65

    Article  CAS  Google Scholar 

  • Autian J (1982) Antifertility effects and dominant lethal assays for mutagenic effects of DEHP. Environ Health Perspect 45:115–118

    Article  CAS  Google Scholar 

  • Aydoĝan Ahbab M, Barlas N (2013) Developmental effects of prenatal di-n-hexyl phthalate and dicyclohexyl phthalate exposure on reproductive tract of male rats: postnatal outcomes. Food Chem Toxicol 51:123–136

    Article  CAS  Google Scholar 

  • Baek IJ et al. (2007) Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes. J Vet Sci 8:213–218

    Article  Google Scholar 

  • Bajkin I, Bjelica A, Icin T, Dobrić V, Zavisić BK, Stojanoska MM (2014) Effects of phthalic acid esters on fetal health. Med Pregl 67(5–6):172–175

    Article  Google Scholar 

  • Borch J, Metzdorff SB, Vinggaard AM, Brokken L, Dalgaard M (2006) Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Toxicology 223:144–155. doi:10.1016/j.tox.2006.03.015

    Article  CAS  Google Scholar 

  • Bornehag CG, Sundell J, Weschler CJ, Sigsgaard T, Lundgren B, Hasselgren M, Hagerhed-Engman L (2004) The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case-control study. Environ Health Perspect 112:1393–1397

    Article  CAS  Google Scholar 

  • Botelho GGK, Golin M, Bufalo AC, Morais RN, Dalsenter PR, Martino-Andrade AJ (2009) Reproductive effects of di(2-ethylhexyl)phthalate in immature male rats and its relation to cholesterol, testosterone, and thyroxin levels. Arch Environ Contam Toxicol 57:777–784

    Article  CAS  Google Scholar 

  • Cai Q (2016) Telomere length: a possible link between phthalate exposure and cancer development? EBioMedicine 6:6–7

    Article  Google Scholar 

  • Caldwell JC (2012) DEHP: genotoxicity and potential carcinogenic mechanisms—a review. Mutat Res 751:82–157

    Article  CAS  Google Scholar 

  • Cammack JN et al. (2003) Evaluation of reproductive development following intravenous and oral exposure to DEHP in male neonatal rats. Int J Toxicol 22:159–174

    Article  CAS  Google Scholar 

  • Carbone S et al. (2010) Impact of gestational and lactational phthalate exposure on hypothalamic content of amino acid neurotransmitters and FSH secretion in peripubertal male rats. Neurotoxicology 31:747–751

    Article  CAS  Google Scholar 

  • Carbone S et al. (2012) Different effects by sex on hypothalamic-pituitary axis of prepubertal offspring rats produced by in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP). Neurotoxicology 33:78–84

    Article  CAS  Google Scholar 

  • Carbone S et al. (2013) Antiandrogenic effect of perinatal exposure to the endocrine disruptor di-(2-ethylhexyl) phthalate increases anxiety-like behavior in male rats during sexual maturation. Horm Behav 63:692–699

    Article  CAS  Google Scholar 

  • Carnevali O, Tosti L, Speciale C, Peng C, Zhu Y, Maradonna F (2010) DEHP impairs zebrafish reproduction by affecting critical factors in oogenesis. PLoS One 5:e10201. doi:10.1371/journal.pone.0010201

    Article  CAS  Google Scholar 

  • Cattley RC, Conway JG, Popp JA (1987) Association of persistent peroxisome proliferation and oxidative injury with hepatocarcinogenicity in female F-344 rats fed di(2-ethylhexyl) phthalate for 2 years. Cancer Lett 38:15–22

    Article  CAS  Google Scholar 

  • Chen FP, Chien MH (2014) Lower concentrations of phthalates induce proliferation in human breast cancer cells. Climacteric 17:377–384

    Article  CAS  Google Scholar 

  • Chen SQ et al. (2010) Perinatal exposure to di-(2-ethylhexyl) phthalate leads to restricted growth and delayed lung maturation in newborn rats. J Perinat Med 38:515–521. doi:10.1515/jpm.2010.083

    Article  CAS  Google Scholar 

  • Corradetti B, Stronati A, Tosti L, Manicardi G, Carnevali O, Bizzaro D (2013) Bis-(2-ethylexhyl) phthalate impairs spermatogenesis in zebrafish (Danio rerio. Reprod Biol 13:195–202. doi:10.1016/j.repbio.2013.07.003

    Article  Google Scholar 

  • Culty M et al. (2008) In utero exposure to di-(2-ethylhexyl) phthalate exerts both short-term and long-lasting suppressive effects on testosterone production in the rat. Biol Reprod 78:1018–1028. doi:10.1095/biolreprod.107.065649

    Article  CAS  Google Scholar 

  • Curto KA, Thomas JA (1982) Comparative effects of diethylhexyl phthalate or monoethylhexyl phthalate on male mouse and rat reproductive organs. Toxicol Appl Pharmacol 62:121–125

    Article  CAS  Google Scholar 

  • Dalsenter PR, Santana GM, Grande SW, Andrade AJ, Araujo SL (2006) Phthalate affect the reproductive function and sexual behavior of male Wistar rats. Hum Exp Toxicol 25:297–303

    Article  CAS  Google Scholar 

  • David RM, Moore MR, Cifone MA, Finney DC, Guest D (1999) Chronic peroxisome proliferation and hepatomegaly associated with the hepatocellular tumorigenesis of di(2-ethylhexyl)phthalate and the effects of recovery. Toxicol Sci 50:195–205

    Article  CAS  Google Scholar 

  • David RM, Moore MR, Finney DC, Guest D (2000) Chronic toxicity of di(2-ethylhexyl)phthalate in rats. Toxicol Sci 55:433–443

    Article  CAS  Google Scholar 

  • David RM, Moore MR, Finney DC, Guest D (2001) Reversibility of the chronic effects of di(2-ethylhexyl)phthalate. Toxicol Pathol 29:430–439

    Article  CAS  Google Scholar 

  • Deangelo AB, Garrett CT (1983) Inhibition of development of preneoplastic lesions in the livers of rats fed a weakly carcinogenic environmental contaminant. Cancer Lett 20:199–205

    Article  CAS  Google Scholar 

  • DeAngelo AB, Queral AE, Garrett CT (1985) Concentration-dependent inhibition of development of GGT positive foci in rat liver by the environmental contaminant di(2-ethylhexyl) phthalate. Environ Health Perspect 60:381–385

    Article  CAS  Google Scholar 

  • Diwan BA, Ward JM, Rice JM, Colburn NH, Spangler EF (1985) Tumor-promoting effects of di(2-ethylhexyl) phthalate in JB6 mouse epidermal cells and mouse skin. Carcinogenesis 6:343–347

    Article  CAS  Google Scholar 

  • Dobrzyńska MM, Tyrkiel EJ, Derezińska E, Pachocki KA, Ludwicki JK (2012) Two generation reproductive and developmental toxicity following subchronic exposure of pubescent male mice to di(2-ethylhexyl) phthalate. Ann Agric Environ Med 19:31–37

    Google Scholar 

  • Dorostghoal M, Moazedi AA, Zardkaf A (2012) Long-term effects of maternal exposure to di (2-ethylhexyl) phthalate on sperm and testicular parameters in wistar rats offspring. Iran J Reprod Med 10:7–14

    CAS  Google Scholar 

  • Doyle TJ, Bowman JL, Windell VL, McLean DJ, Kim KH (2013) Transgenerational effects of di-(2-ethylhexyl) phthalate on testicular germ cell associations and spermatogonial stem cells in mice. Biol Reprod 88:112. doi:10.1095/biolreprod.112.106104

    Article  Google Scholar 

  • Fahrig R, Steinkamp-Zucht A (1996) Co-recombinogenic and anti-mutagenic effects of diethylhexylphthalate, inactiveness of pentachlorophenol in the spot test with mice. Mutat Res 354:59–67

    Article  Google Scholar 

  • Ferguson KK, McElrath TF, Meeker JD (2014) Environmental phthalate exposure and preterm birth. JAMA Pediatr 168:61–67. doi:10.1001/jamapediatrics.2013.3699

    Article  Google Scholar 

  • Garvey LK, Swenberg JA, Hamm TE Jr, Popp JA (1987) Di(2-ethylhexyl)phthalate: lack of initiating activity in the liver of female F-344 rats. Carcinogenesis 8:285–290

    Article  CAS  Google Scholar 

  • Gascon M, Valvi D, Forns J, Casas M, Martínez D, Júlvez J, Monfort N, Ventura R, Sunyer J, Vrijheid M (2015) Prenatal exposure to phthalates and neuropsychologicaldevelopment during childhood. Int J Hyg Environ Health 218(6):550–558

    Article  CAS  Google Scholar 

  • Gaspar FW, Castorina R, Maddalena RL, Nishioka MG, McKone TE, Bradman A (2014) Phthalate exposure and risk assessment in California child care facilities. Environ Sci Technol 48:7593–7601

    Article  CAS  Google Scholar 

  • Grande SW, Andrade AJ, Talsness CE, Grote K, Chahoud I (2006) A dose-response study following in utero and lactational exposure to di(2-ethylhexyl)phthalate: effects on female rat reproductive development. Toxicol Sci 91:247–254. doi:10.1093/toxsci/kfj128

    Article  CAS  Google Scholar 

  • Gray LE, Ostby J, Furr J, Price M, Veeramachaneni DR, Parks L (2000) Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci 58:350–365

    Article  CAS  Google Scholar 

  • Gray LE Jr, Barlow NJ, Howdeshell KL, Ostby JS, Furr JR, Gray CL (2009) Transgenerational effects of di (2-ethylhexyl) phthalate in the male CRL:CD(SD) rat: added value of assessing multiple offspring per litter. Toxicol Sci 110:411–425

    Article  CAS  Google Scholar 

  • Guo J et al. (2012) Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl) phthalate in ovalbumin-immunized BALB/c mice. PLoS One 7:e39008. doi:10.1371/journal.pone.0039008

    Article  CAS  Google Scholar 

  • Gupta RK, Singh JM, Leslie TC, Meachum S, Flaws JA, Yao HHC (2010) Di-(2-ethylhexyl) phthalate and mono-(2-ethylhexyl) phthalate inhibit growth and reduce estradiol levels of antral follicles in vitro. Toxicol Appl Pharmacol 242:224–230

    Article  CAS  Google Scholar 

  • Habib MR, Karim MR (2012) Antitumour evaluation of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea L. flower. Acta Pharma 62:607–615. doi:10.2478/v10007-012-0035-9

    Article  CAS  Google Scholar 

  • Han SW et al. (2009) An exposure assessment of DI-(2-ethylhexyl) phthalate (DEHP) and DI-n-butyl phthalate (DBP) in human semen. J Toxicol Environ Health A 72:1463–1469

    Article  CAS  Google Scholar 

  • Hannas BR, Lambright CS, Furr J, Howdeshell KL, Wilson VS, Gray LE Jr (2011) Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate. Toxicol Sci 123:206–216. doi:10.1093/toxsci/kfr146

    Article  CAS  Google Scholar 

  • Hannon PR, Flaws JA (2015) The effects of phthalates on the ovary. Front Endocrinol (Lausanne) 2;6:8

    Google Scholar 

  • Hansen DK, Grafton TF (1994) Devaluation of di(2-ethylhexyl)phthalate-induced embryotoxicity in rodent whole-embryo culture. J Toxicol Environ Health 43:361–367

    Article  CAS  Google Scholar 

  • Hart RJ (2016) Physiological aspects of female fertility: role of the environment, modern lifestyle, and genetics. Physiol Rev 96(3):873–909

    Article  Google Scholar 

  • Hauser R, Calafat A (2005) Phthalates and human health. Occup Environ Med 62:806–818

    Article  CAS  Google Scholar 

  • Hayashi Y et al. (2011) Hepatic peroxisome proliferator-activated receptor α may have an important role in the toxic effects of di(2-ethylhexyl)phthalate on offspring of mice. Toxicology 289:1–10

    Article  CAS  Google Scholar 

  • Herreros M, Gonzalez-Bulnes A, Inigo-Nunez S, Letelier C, Contreras-Solis I, Ros-Rodriguez J, Encinas T (2010) Pregnancy-associated changes in plasma concentration of the endocrine disruptor di (2-ethylhexyl) phthalate in a sheep model. Theriogenology 73:141–146

    Article  CAS  Google Scholar 

  • Hoyer PB (2001) Reproductive toxicology: current and future directions. Biochem Pharmacol 62:1557–1564

    Article  CAS  Google Scholar 

  • Hsu YL, Hung JY, Tsai EM, CY W, Ho YW, Jian SF, Yen MC, Chang WA, Hou MF, Kuo PL (2015) Benzyl butyl phthalate increases the chemoresistance to doxorubicin/cyclophosphamide by increasing breast cancer-associated dendritic cell-derived CXCL1/GROα and S100A8/A9. Oncol Rep 34(6):2889–2900

    Google Scholar 

  • Hsu YL, Hsieh CJ, Tsai EM, Hung JY, Chang WA, Hou MF, Kuo PL (2016) Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment. Oncol Lett 11(2):1035–1042

    Google Scholar 

  • Huang XF et al. (2012) The effects of di-(2-ethylhexyl)-phthalate exposure on fertilization and embryonic development in vitro and testicular genomic mutation in vivo. PLoS One 7:e50465. doi:10.1371/journal.pone.0050465

    Article  CAS  Google Scholar 

  • Huang Y, Li J, Garcia JM, Lin H, Wang Y, Yan P, Wang L, Tan Y, Luo J, Qiu Z, Chen JA, Shu W (2014) Phthalate levels in cord blood are associated with preterm delivery and fetal growth parameters in Chinese women. PLoS One 9(2):e87430

    Article  CAS  Google Scholar 

  • Isenberg JS et al. (2001) Reversibility and persistence of di-2-ethylhexyl phthalate (DEHP)- and phenobarbital-induced hepatocellular changes in rodents. Toxicol Sci 64:192–199

    Article  CAS  Google Scholar 

  • Jensen MS et al. (2012) Phthalates and perfluorooctanesulfonic acid in human amniotic fluid: temporal trends and timing of amniocentesis in pregnancy. Environ Health Perspect 120:897–903

    Article  CAS  Google Scholar 

  • Jurewicz J, Hanke W (2011) Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies. Int J Occup Med Environ Health 24(2):115–141

    Article  Google Scholar 

  • Kang JS, Morimura K, Toda C, Wanibuchi H, Wei M, Kojima N, Fukushima S (2006) Testicular toxicity of DEHP, but not DEHA, is elevated under conditions of thioacetamide-induced liver damage. Reprod Toxicol 21:253–259. doi:10.1016/j.reprotox.2005.09.013

    Article  CAS  Google Scholar 

  • Kavlock R et al. (2002a) NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di-n-octyl phthalate. Reprod Toxicol 16:721–734

    Article  CAS  Google Scholar 

  • Kavlock R et al. (2002b) NTP Center for the Evaluation of Risks to Human Reproduction: phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl) phthalate. Reprod Toxicol 16:529–653

    Article  CAS  Google Scholar 

  • Kavlock R et al. (2006) NTP-CERHR Expert Panel Update on the Reproductive and Developmental Toxicity of di(2-ethylhexyl) phthalate. Reprod Toxicol 22:291–399

    Article  CAS  Google Scholar 

  • Kim EJ, Kim JW, Lee SK (2002) Inhibition of oocyte development in Japanese medaka (Oryzias latipes) exposed to di-2-ethylhexyl phthalate. Environ Int 28:359–365

    Article  CAS  Google Scholar 

  • Kimber I, Dearman RJ (2010) An assessment of the ability of phthalates to influence immune and allergic responses. Toxicology 271:73–82. doi:10.1016/j.tox.2010.03.020

    Article  CAS  Google Scholar 

  • Kitaoka M et al. (2013) Effects on the local immunity in the testis by exposure to di-(2-ethylhexyl) phthalate (DEHP) in mice. J Reprod Dev 59:485–490

    Article  CAS  Google Scholar 

  • Klimisch HJ, Gamer AO, Hellwig J, Kaufmann W, Jackh R (1992) Di-(2-ethylhexyl) phthalate: a short-term repeated inhalation toxicity study including fertility assessment. Food Chem Toxicol 30:915–919

    Article  CAS  Google Scholar 

  • Klinefelter GR et al. (2012) Novel molecular targets associated with testicular dysgenesis induced by gestational exposure to diethylhexyl phthalate in the rat: a role for estradiol. Reproduction 144:747–761. doi:10.1530/rep-12-0266

    Article  CAS  Google Scholar 

  • Kluwe WM, Haseman JK, Douglas JF, Huff JE (1982) The carcinogenicity of dietary di(2-ethylhexyl) phthalate (DEHP) in Fischer 344 rats and B6C3F1 mice. J Toxicol Environ Health 10:797–815. doi:10.1080/15287398209530296

    Article  CAS  Google Scholar 

  • Koike E, Inoue K, Yanagisawa R, Takano H (2009) Di-(2-ethylhexyl) phthalate affects immune cells from atopic prone mice in vitro. Toxicology 259:54–60

    Article  CAS  Google Scholar 

  • Kolarik B, Naydenov K, Larsson M, Bornehag CG, Sundell J (2008) The association between phthalates in dust and allergic diseases among Bulgarian children. Environ Health Perspect 116:98–103

    Article  CAS  Google Scholar 

  • Kranvogl R, Knez J, Miuc A, Vončina E, Vončina DB, Vlaisavljević V (2014) Simultaneous determination of phthalates, their metabolites, alkylphenols and bisphenol a using GC-MS in urine of men with fertility problems. Acta Chim Slov 61:110–120

    CAS  Google Scholar 

  • Lamb JC, Chapin RE, Teague J, Lawton AD, Reel JR (1987) Reproductive effects of four phthalic acid esters in the mouse. Toxicol Appl Pharmacol 88:255–269

    Article  CAS  Google Scholar 

  • Larsen ST, Hansen JS, Hansen EW, Clausen PA, Nielsen GD (2007) Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl) phthalate and ovalbumin in BALB/c mice. Toxicology 235:119–129

    Article  CAS  Google Scholar 

  • Latini G, De Felice C, Presta G, Del Vecchio A, Paris I, Ruggieri F, Mazzeo P (2003a) Exposure to di(2-ethylhexyl)phthalate in humans during pregnancy. A preliminary report. Biol Neonate 83:22–24

  • Latini G, De Felice C, Presta G, Del Vecchio A, Paris I, Ruggieri F, Mzzeo P (2003b) In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environ Health Perspect 111:1783–1785

    Article  CAS  Google Scholar 

  • Lewandowski M, Fernandes J, Chen TS (1980) Assessment of the teratogenic potential of plasma-soluble extracts of diethylhexyl phthalate plasticized polyvinyl chloride plastics in rats. Toxicol Appl Pharmacol 54:141–147

    Article  CAS  Google Scholar 

  • Li S, Dai J, Zhang L, Zhang J, Zhang Z, Chen B (2011) An association of elevated serum prolactin with phthalate exposure in adult men. Biomed Environ Sci 24:31–39

    CAS  Google Scholar 

  • Li R et al. (2012) Effects of DEHP on endometrial receptivity and embryo implantation in pregnant mice. J Hazard Mater 241-242:231–240. doi:10.1016/j.jhazmat.2012.09.038

    Article  CAS  Google Scholar 

  • Li M et al. (2013) Dose-related effect by maternal exposure to di-(2-ethylhexyl) phthalate plasticizer on inducing hypospadiac male rats. Environ Toxicol Pharmacol 35:55–60. doi:10.1016/j.etap.2012.10.006

    Article  CAS  Google Scholar 

  • Liberati A et al. (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W-65–W-94

    Article  Google Scholar 

  • Lin H et al. (2008) Involvement of testicular growth factors in fetal Leydig cell aggregation after exposure to phthalate in utero. Proc Natl Acad Sci U S A 105:7218–7222. doi:10.1073/pnas.0709260105

    Article  CAS  Google Scholar 

  • Liu X, He DW, Zhang DY, Lin T, Wei GH (2008) Di (2-ethylhexyl) phthalate (DEHP) increases transforming growth factor-β1 expression in fetal mouse genital tubercles. J Toxicol Environ Health A 71:1289–1294

    Article  CAS  Google Scholar 

  • Luisi S, Latini G, de Felice C, Sanseverino F, di Pasquale D, Mazzeo P, Petraglia F (2006) Low serum concentrations of di-(2-ethylhexyl)phthalate in women with uterine fibromatosis. Gynecol Endocrinol 22:92–95. doi:10.1080/09513590600551312

    Article  CAS  Google Scholar 

  • Ma M, Kondo T, Ban S, Umemura T, Kurahashi N, Takeda M, Kishi R (2006) Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions. Toxicol Sci 93:164–171. doi:10.1093/toxsci/kfl036

    Article  CAS  Google Scholar 

  • Magliozzi R, Nardacci R, Scarsella G, Di Carlo V, Stefanini S (2003) Effects of the plasticiser DEHP on lung of newborn rats: catalase immunocytochemistry and morphometric analysis. Histochem Cell Biol 120:41–49. doi:10.1007/s00418-003-0543-2

    Article  CAS  Google Scholar 

  • Maranghi F et al. (2010) In utero exposure to di-(2-ethylhexyl) phthalate affects liver morphology and metabolism in post-natal CD-1 mice. Reprod Toxicol 29:427–432. doi:10.1016/j.reprotox.2010.03.002

    Article  CAS  Google Scholar 

  • Marie C, Vendittelli F, Sauvant-Rochat MP (2015) Obstetrical outcomes and biomarkers to assess exposure to phthalates: a review. Environ Int 83:116–136

    Article  CAS  Google Scholar 

  • Martinez-Arguelles DB, Culty M, Zirkin BR, Papadopoulos V (2009) In utero exposure to di-(2-ethylhexyl) phthalate decreases mineralocorticoid receptor expression in the adult testis. Endocrinology 150:5575–5585. doi:10.1210/en.2009-0847

    Article  CAS  Google Scholar 

  • Martinez-Arguelles DB, Guichard T, Culty M, Zirkin BR, Papadopoulos V (2011) In utero exposure to the antiandrogen di-(2-ethylhexyl) phthalate decreases adrenal aldosterone production in the adult rat. Biol Reprod 85:51–61. doi:10.1095/biolreprod.110.089920

    Article  CAS  Google Scholar 

  • Martino-Andrade AJ et al. (2009) Coadministration of active phthalates results in disruption of foetal testicular function in rats. Int J Androl 32:704–712

    Article  CAS  Google Scholar 

  • Mathieu-Denoncourt J, Wallace SJ, de Solla SR, Langlois VS (2015) Plasticizer endocrine disruption: highlighting developmental and reproductive effects in mammals and non-mammalian aquatic species. Gen Comp Endocrinol 1;219:74–88

    Article  CAS  Google Scholar 

  • Matsumoto M, Hirata-Koizumi M, Ema M (2008) Potential adverse effects of phthalic acid esters on human health: a review of recent studies on reproduction. Regul Toxicol Pharmacol 50:37–49

    Article  CAS  Google Scholar 

  • McKee R, El-Hawari M, Stoltz M, Pallas F, Lington A (2002) Absorption, disposition and metabolism of di-isononyl phthalate (DINP) in F-344 rats. J Appl Toxicol 22:293–302

    Article  CAS  Google Scholar 

  • Merkle J, Klimisch HJ, Jackh R (1988) Developmental toxicity in rats after inhalation exposure of di-2-ethylhexylphthalate (DEHP. Toxicol Lett 42:215–223

    Article  CAS  Google Scholar 

  • Mitchell FE, Price SC, Hinton RH, Grasso P, Bridges JW (1985) Time and dose-response study of the effects on rats of the plasticizer di(2-ethylhexyl) phthalate. Toxicol Appl Pharmacol 81:371–392

    Article  CAS  Google Scholar 

  • Modigh CM, Bodin SLV, Lillienberg L, Dahlman-Höglund A, Åkesson B, Axelsson G (2002) Time to pregnancy among partners of men exposed to di(2-ethylhexyl)phthalate. Scand J Work Environ Health 28:418–428

    Article  CAS  Google Scholar 

  • Moore RW, Rudy TA, Lin TM, Ko K, Peterson RE (2001) Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer di(2-ethylhexyl) phthalate. Environ Health Perspect 109:229–237

    Article  CAS  Google Scholar 

  • Mortensen A, Bertram M, Aarup V, Sorensen IK (2002) Assessment of carcinogenicity of di(2-ethylhexyl)phthalate in a short-term assay using Xpa−/− and Xpa−/−/p53+/− mice. Toxicol Pathol 30:188–199

    Article  CAS  Google Scholar 

  • Nikonorow M, Mazur H, Piekacz H (1973) Effect of orally administered plasticizers and polyvinyl chloride stabilizers in the rat. Toxicol Appl Pharmacol 26:253–259

    Article  CAS  Google Scholar 

  • Norback D, Wieslander G, Nordstrom K, Walinder R (2000) Asthma symptoms in relation to measured building dampness in upper concrete floor construction, and 2-ethyl-1-hexanol in indoor air. Int J Tuberc Lung Dis 4:1016–1025

    CAS  Google Scholar 

  • North ML, Takaro TK, Diamond ML, Ellis AK (2014) Effects of phthalates on the development and expression of allergic disease and asthma. Ann Allergy Asthma Immunol 112:496–502

    Article  CAS  Google Scholar 

  • Oie L, Hersoug LG, Madsen JO (1997) Residential exposure to plasticizers and its possible role in the pathogenesis of asthma. Environ Health Perspect 105:972–978

    Article  CAS  Google Scholar 

  • Oishi S (1986) Testicular atrophy induced by di(2-ethylhexyl)phthalate: changes in histology, cell specific enzyme activities and zinc concentrations in rat testis. Arch Toxicol 59:290–295

    Article  CAS  Google Scholar 

  • Pan G et al. (2006) 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 114:1643–1648

    CAS  Google Scholar 

  • Parillo F, Maranesi M, Brecchia G, Gobbetti A, Boiti C, Zerani M (2014) In vivo chronic and in vitro acute effects of di(2-ethylhexyl) phthalate on pseudopregnant rabbit corpora lutea: possible involvement of peroxisome proliferator-activated receptor gamma 90

  • Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, Gray LE Jr (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58:339–349

    Article  CAS  Google Scholar 

  • Parmar D, Srivastava SP, Seth PK (1986) Effect of di(2-ethylhexyl)phthalate (DEHP) on spermatogenesis in adult rats. Toxicology 42:47–55

    Article  CAS  Google Scholar 

  • Parmar D, Srivastava SP, Singh GB, Seth PK (1995) Testicular toxicity of di(2-ethylhexyl)phthalate in developing rats. Vet Hum Toxicol 37:310–313

    CAS  Google Scholar 

  • Patel S, Zhou C, Rattan S, Flaws JA (2015) Effects of endocrine-disrupting chemicals on the ovary. Biol Reprod 93(1):20

    Article  CAS  Google Scholar 

  • Peters JM, Taubeneck MW, Keen CL, Gonzalez FJ (1997) Di(2-ethylhexyl) phthalate induces a functional zinc deficiency during pregnancy and teratogenesis that is independent of peroxisome proliferator-activated receptor-alpha. Teratology 56:311–316

    Article  CAS  Google Scholar 

  • Popp JA, Garvey LK, Hamm TE Jr, Swenberg JA (1985) Lack of hepatic promotional activity by the peroxisomal proliferating hepatocarcinogen di(2-ethylhexyl)phthalate. Carcinogenesis 6:141–144

    Article  CAS  Google Scholar 

  • Rao MS, Usuda N, Subbarao V, Reddy JK (1987) Absence of gamma-glutamyl transpeptidase activity in neoplastic lesions induced in the liver of male F-344 rats by di-(2-ethylhexyl)phthalate, a peroxisome proliferator. Carcinogenesis 8:1347–1350

    Article  CAS  Google Scholar 

  • Rao MS, Yeldandi AV, Subbarao V (1990) Quantitative analysis of hepatocellular lesions induced by di(2-ethylhexyl)phthalate in F-344 rats. J Toxicol Environ Health 30:85–89. doi:10.1080/15287399009531413

    Article  CAS  Google Scholar 

  • Reddy BS, Rozati R, Reddy BVR, Raman NVVSS (2006) Association of phthalate esters with endometriosis in Indian women. BJOG 113:515–520

    Article  CAS  Google Scholar 

  • Roh JY, Jung IH, Lee JY, Choi J (2007) Toxic effects of di(2-ethylhexyl)phthalate on mortality, growth, reproduction and stress-related gene expression in the soil nematode Caenorhabditis elegans. Toxicology 237:126–133. doi:10.1016/j.tox.2007.05.008

    Article  CAS  Google Scholar 

  • Romani F et al. (2014) Endocrine disruptors and human reproductive failure: the in vitro effect of phthalates on human luteal cells. Fertil Steril 102:831–837

    Article  CAS  Google Scholar 

  • Rosicarelli B, Stefanini S (2009) DEHP effects on histology and cell proliferation in lung of newborn rats. Histochem Cell Biol 131:491–500. doi:10.1007/s00418-008-0550-4

    Article  CAS  Google Scholar 

  • Rozati R, Simha B, Bendi N, Sekhar C (2008) Evaluation of the phthalate esters in South Indian women with endometriosis, 1:165–170

  • Rusyn I, Corton JC (2012) Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate. Mutat Res 750:141–158

    Article  CAS  Google Scholar 

  • Saillenfait AM, Gallissot F, Sabaté JP (2009a) Differential developmental toxicities of di-n-hexyl phthalate and dicyclohexyl phthalate administered orally to rats, 29:510–521

  • Saillenfait, AM, Sabaté JP, Gallissot F (2009b) Effects of in utero exposure to di-n-hexyl phthalate on the reproductive development of the male rat, 28:468–476

  • Saillenfait AM, Roudot AC, Gallissot F, Sabate JP (2011) Prenatal developmental toxicity studies on di-n-heptyl and di-n-octyl phthalates in Sprague-Dawley rats. Reprod Toxicol 32:268–276. doi:10.1016/j.reprotox.2011.08.001

    Article  CAS  Google Scholar 

  • Saillenfait AM, Sabaté JP, Robert A, Rouiller-Fabre V, Roudot AC, Moison D, Denis F (2013) Dose-dependent alterations in gene expression and testosterone production in fetal rat testis after exposure to di-n-hexyl phthalate, 33:1027–1035

  • Schmidt JS, Schaedlich K, Fiandanese N, Pocar P, Fischer B (2012) Effects of di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis in C3H/N mice. Environ Health Perspect 120:1123–1129. doi:10.1289/ehp.1104016

    Article  CAS  Google Scholar 

  • Scinicariello F, Buser MC (2015) Polychlorinated biphenyls and leukocyte telomere length: an analysis of NHANES 1999-2002. EBioMedicine 2(12):1974–1979

    Article  Google Scholar 

  • Sekiguchi S, Ito S, Honma T (2003) Experimental model to study reproductive toxicity of chemicals using induced ovulation in immature F344 rats. Ind Health 41:287–290

    Article  CAS  Google Scholar 

  • Serrano SE et al. (2014) Dietary phthalate exposure in pregnant women and the impact of consumer practices, 11:6193–6215

  • Shin IS, Lee MY, Cho ES, Choi EY, Son HY, Lee KY (2014) Effects of maternal exposure to di(2-ethylhexyl)phthalate (DEHP) during pregnancy on susceptibility to neonatal asthma. Toxicol Appl Pharmacol 274:402–407. doi:10.1016/j.taap.2013.12.009

    Article  CAS  Google Scholar 

  • Shioda T, Wakabayashi M (2000) Effect of certain chemicals on the reproduction of medaka (Oryzias latipes. Chemosphere 40:239–243

    Article  CAS  Google Scholar 

  • Shiota K, Mima S (1985) Assessment of the teratogenicity of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in mice. Arch Toxicol 56:263–266

    Article  CAS  Google Scholar 

  • Shiota K, Nishimura H (1982) Teratogenicity of di(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DBP) in mice. Environ Health Perspect 45:65–70

    Article  CAS  Google Scholar 

  • Shirota M et al. (2005) Influence of di-(2-ethylhexyl)phthalate on fetal testicular development by oral administration to pregnant rats. J Toxicol Sci 30:175–194

    Article  CAS  Google Scholar 

  • Singh AR, Lawrence WH, Autian J (1974) Mutagenic and antifertility sensitivities of mice to di-2-ethylhexyl phthalate (DEHP) and dimethoxyethyl phthalate (DMEP. Toxicol Appl Pharmacol 29:35–46

    Article  CAS  Google Scholar 

  • Spjuth L, Ljungvall K, Saravia F, Lundeheim N, Magnusson U, Hultén F, Rodríguez-Martínez H (2006) Does exposure to di(2-ethylhexyl) phthalate in pre-pubertal boars affect semen quality post-puberty? 29:534–542

  • Spjuth L et al. (2007a) Pre-pubertal di(2-ethylhexyl) phthalate (DEHP) exposure of young boars did not affect sperm in vitro penetration capacity of homologous oocytes post-puberty. Arch Androl 53:141–147. doi:10.1080/01485010701271778

    Article  CAS  Google Scholar 

  • Spjuth L, Johannisson A, Lundeheim N, Rodriguez-Martinez H (2007b) Early pre-pubertal exposure to low-dose oral di(2-ethylhexyl) phthalate does not affect sperm plasma membrane stability, acrosomal integrity or chromatin structure in the post-pubertal boar. Theriogenology 68:186–195. doi:10.1016/j.theriogenology.2007.04.051

    Article  CAS  Google Scholar 

  • Stroheker T, Regnier JF, Lassurguere J, Chagnon MC (2006) Effect of in utero exposure to di-(2-ethylhexyl)phthalate: distribution in the rat fetus and testosterone production by rat fetal testis in culture. Food Chem Toxicol 44:2064–2069. doi:10.1016/j.fct.2006.07.007

    Article  CAS  Google Scholar 

  • Suzuki Y, Yoshinaga J, Mizumoto Y, Serizawa S, Shiraishi H (2012) Foetal exposure to phthalate esters and anogenital distance in male newborns. Int J Androl 35:236–244

    Article  CAS  Google Scholar 

  • Svechnikova I, Svechnikov K, Söder O (2007) The influence of di-(2-ethylhexyl) phthalate on steroidogenesis by the ovarian granulosa cells of immature female rats, 194:603–609

  • Swan SH et al. (2005) Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect:1056–1061

  • Takashima K, Ito Y, Gonzalez FJ, Nakajima T (2008) Different mechanisms of DEHP-induced hepatocellular adenoma tumorigenesis in wild-type and Ppar alpha-null mice. J Occup Health 50:169–180

    Article  CAS  Google Scholar 

  • Takeshita A, Inagaki K, Igarashi-Migitaka J, Ozawa Y, Koibuchi N (2006) The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells, 190:897–902

  • Tanaka T (2002) Reproductive and neurobehavioural toxicity study of bis(2-ethylhexyl) phthalate (DEHP) administered to mice in the diet. Food Chem Toxicol 40:1499–1506

    Article  CAS  Google Scholar 

  • Tanaka T (2005) Reproductive and neurobehavioural effects of bis(2-ethylhexyl) phthalate (DEHP) in a cross-mating toxicity study of mice. Food Chem Toxicol 43:581–589. doi:10.1016/j.fct.2005.01.001

    Article  CAS  Google Scholar 

  • Tarlo SM (2003) Workplace irritant exposures: do they produce true occupational asthma? Annals of Allergy, Asthma & Immunology 90:19–23

  • Téllez-Rojo MM, Cantoral A, Cantonwine DE, Schnaas L, Peterson K, Hu H, Meeker JD (2013) Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age. Sci Total Environ 461-462:386–390

    Article  CAS  Google Scholar 

  • Tomita I, Nakamura Y, Aoki N, Inui N (1982) Mutagenic/carcinogenic potential of DEHP and MEHP. Environ Health Perspect 45:119–125

    Article  CAS  Google Scholar 

  • Toyosawa K et al. (2001) Di(2-ethylhexyl)phthalate induces hepatocellular adenoma in transgenic mice carrying a human prototype c-Ha-ras gene in a 26-week carcinogenicity study. Toxicol Pathol 29:458–466

    Article  CAS  Google Scholar 

  • Tsutsui T, Watanabe E, Barrett JC (1993) Ability of peroxisome proliferators to induce cell transformation, chromosome aberrations and peroxisome proliferation in cultured Syrian hamster embryo cells. Carcinogenesis 14:611–618

    Article  CAS  Google Scholar 

  • Tyl RW, Price CJ, Marr MC, Kimmel CA (1988) Developmental toxicity evaluation of dietary di(2-ethylhexyl)phthalate in Fischer 344 rats and CD-1 mice. Fundam Appl Toxicol 10:395–412

    Article  CAS  Google Scholar 

  • Uren-Webster TM, Lewis C, Filby AL, Paull GC, Santos EM (2010) Mechanisms of toxicity of di(2-ethylhexyl) phthalate on the reproductive health of male zebrafish. Aquat Toxicol 99:360–369. doi:10.1016/j.aquatox.2010.05.015

    Article  CAS  Google Scholar 

  • Ventrice P, Ventrice D, Russo E, De Sarro G (2013) Phthalates: European regulation, chemistry, pharmacokinetic and related toxicity, 36:88–96

  • Voss C, Zerban H, Bannasch P, Berger MR (2005) Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats. Toxicology 206:359–371. doi:10.1016/j.tox.2004.07.016

    Article  CAS  Google Scholar 

  • Wang W, Wu FY, Huang MJ, Kang Y, Cheung KC, Wong MH (2013) Size fraction effect on phthalate esters accumulation, bioaccessibility and in vitro cytotoxicity of indoor/outdoor dust, and risk assessment of human exposure, 261:753–762

  • Wang YC, Tsai CF, Chuang HL, Chang YC, Chen HS, Lee JN, Tsai EM (2016) Benzyl butyl phthalate promotes breast cancer stem cell expansion via SPHK1/S1P/S1PR3 signaling. Oncotarget. doi:10.18632/oncotarget.9007

    Google Scholar 

  • Ward JM, Ohshima M, Lynch P, Riggs C (1984) Di(2-ethylhexyl)phthalate but not phenobarbital promotes N-nitrosodiethylamine-initiated hepatocellular proliferative lesions after short-term exposure in male B6C3F1 mice. Cancer Lett 24:49–55

    Article  CAS  Google Scholar 

  • Ward JM, Diwan BA, Ohshima M, Hu H, Schuller HM, Rice JM (1986) Tumor-initiating and promoting activities of di(2-ethylhexyl) phthalate in vivo and in vitro. Environ Health Perspect 65:279–291

    CAS  Google Scholar 

  • Ward JM, Peters JM, Perella CM, Gonzalez FJ (1998) Receptor and nonreceptor-mediated organ-specific toxicity of di (2-ethylhexyl) phthalate (DEHP) in peroxisome proliferator-activated receptorα-null mice. Toxicol Pathol 26:240–246

    Article  CAS  Google Scholar 

  • Whyatt RM et al. (2009) Prenatal di(2-ethylhexyl)phthalate exposure and length of gestation among an inner-city cohort. Pediatrics 124:e1213–e1220. doi:10.1542/peds.2009-0325

    Article  Google Scholar 

  • Whyatt RM, Liu X, Rauh VA, Calafat AM, Just AC, Hoepner L, Diaz D, Quinn J, Adibi J, Perera FP, Factor-Litvak P (2012) Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor, and behavioral development at 3 years of age. Environ Health Perspect 120(2):290–295

    Article  CAS  Google Scholar 

  • Williams GM, Maruyama H, Tanaka T (1987) Lack of rapid initiating, promoting or sequential syncarcinogenic effects of di(2-ethylhexyl)phthalate in rat liver carcinogenesis. Carcinogenesis 8:875–880

    Article  CAS  Google Scholar 

  • Wilson VS, Lambright C, Furr J, Ostby J, Wood C, Held G, Gray LE Jr (2004) Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicol Lett 146:207–215

    Article  CAS  Google Scholar 

  • Win-Shwe TT, Yanagisawa R, Koike E, Nitta H, Takano H (2013) Expression levels of neuroimmune biomarkers in hypothalamus of allergic mice after phthalate exposure. J Appl Toxicol 33:1070–1078. doi:10.1002/jat.2835

    Article  CAS  Google Scholar 

  • Wolff MS et al. (2014) Phthalate exposure and pubertal development in a longitudinal study of US girls, 29:1558–1566

  • Wu S et al. (2010) Dynamic epigenetic changes involved in testicular toxicity induced by di-2-(ethylhexyl) phthalate in mice. Basic Clin Pharmacol Toxicol 106:118–123. doi:10.1111/j.1742-7843.2009.00483.x

    Article  CAS  Google Scholar 

  • Xi W, Wan HT, Zhao YG, Wong MH, Giesy JP, Wong CK (2011) Effects of perinatal exposure to bisphenol A and di(2-ethylhexyl)-phthalate on gonadal development of male mice. Environ Sci Pollut Res Int 19:2515–2527. doi:10.1007/s11356-012-0827-y

    Article  CAS  Google Scholar 

  • Yanagisawa R, Takano H, Inoue KI, Koike E, Sadakane K, Ichinose T (2008) Effects of maternal exposure to di-(2-ethylhexyl) phthalate during fetal and/or neonatal periods on atopic dermatitis in male offspring 116:1136–1141

  • Ye T, Kang M, Huang Q, Fang C, Chen Y, Shen H, Dong S (2014) Exposure to DEHP and MEHP from hatching to adulthood causes reproductive dysfunction and endocrine disruption in marine medaka (Oryzias melastigma. Aquat Toxicol 146:115–126. doi:10.1016/j.aquatox.2013.10.025

    Article  CAS  Google Scholar 

  • Yong W, Jiao C, Jianhui W, Yan Z, Qi P, Xiu W, Zuyue S, Yunhui Z (2015) Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells. Toxicol in Vitro 32:86–91

    Article  CAS  Google Scholar 

  • You H, Chen S, Mao L, Li B, Yuan Y, Li R, Yang X (2014) The adjuvant effect induced by di-(2-ethylhexyl) phthalate (DEHP) is mediated through oxidative stress in a mouse model of asthma, 71:272–281

  • Zhang Y, Lin L, Cao Y, Chen B, Zheng L, Ge RS (2009) Phthalate levels and low birth weight: a nested case-control study of Chinese newborns. J Pediatr 155:500–504. doi:10.1016/j.jpeds.2009.04.007

    Article  CAS  Google Scholar 

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Acknowledgments

This study was funded by Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences.

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Authors and Affiliations

  1. Pediatrics Department, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Maryam Zarean, Mojtaba Keikha & Roya Kelishadi

  2. Environmental Health Department, Environment Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

    Maryam Zarean, Parinaz Poursafa & Mohammadmehdi Amin

  3. Students’ Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

    Parinaz Poursafa & Pooyan Khalighinejad

  4. Kimia Gostar Saba, Isfahan, Iran

    Pooyan Khalighinejad

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  1. Maryam Zarean
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Correspondence to Parinaz Poursafa.

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Zarean, M., Keikha, M., Poursafa, P. et al. A systematic review on the adverse health effects of di-2-ethylhexyl phthalate. Environ Sci Pollut Res 23, 24642–24693 (2016). https://doi.org/10.1007/s11356-016-7648-3

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