Phthalates — questions of biotoxicity for the human body

А.V. Kubashko, M.M. Gertsiuk, V.A. Deyev

Key words: phthalates, plasticizers, biotoxicity.

Published: 14.03.2018

References:

• Bajkin I., Bjelica A., Icin T. et al. (2014) Effects of phthalic acid esters on fetal health. Med Pregl., 67(5–6): 172–175.
• Becker K., Seiwert M., Angerer J. et al. (2004) DEHP metabolites in urine of children and DEHP in house dust. Int. J. Hyg. Environ. Health., 207(5): 409–417.
• Belfiore A., Genua M., Malaguarnera R. (2009) PPAR-γ Agonists and Their Effects on IGF-I Receptor Signaling: Implications for Cancer. PPAR Res., 2009: 830501.
• Berge A., Cladiere M., Gasperi J. et al. (2013) Meta-analysis of environmental contamination by phthalates. Environ. Sci. Pollut. Res. Int., 20(11): 8057–8076.
• Bornehag C.G., Sundell J., Weschler C.J. et al. (2004) The association between asthma and allergic symptoms in children and phthalates in house dust: a nested case — control study. Environ. Health Perspect., 112(14): 1393–1397.
• Buchta C. Bittner C., Heinal H. et al. (2005) Translfusion-related exposure to the plasticizer di(2-ethylhexyl) phthalate in patients receiving plateletpheresis concentrates. Transfusion, 45: 798–802.
• Buckley J.P., Engel S.M., Braun J.M. et al. (2016) Prenatal phthalate exposures and body mass index among 4- to 7-year-old children: a pooled analysis. Epidemiol., 27(3): 449–458.
• Bui T.T., Giovanoulis G., Cousins A.P. et al. (2015) Human exposure, hazard and risk of alternative plasticizers to phthalate esters. Sci. Total. Environ., 15(541): 451–467.
• Butler A.S., Behrman R.E. (2007) Preterm Birth. Causes, Consequences, and Prevention. National Academies Press (US), Washington (DC), 790 p.
• Calafat A.M., Needham L.L., Silva M.J. et al. (2004) Exposure To di-(2-ethylhexyl) phthalate among prematureneonatesin a neonatalintensivecareunit. Pediatrics, 113: e429–e434.
• Center for Devices and Radiological Health (2001) Safety Assessment of Di(2-ethylhexyl)phthalate (DEHP) Released from PVC Medical Devices (https://www.fda.gov/downloads/MedicalDevices/…/UCM080457.pdf).
• Chen H., Zhang W., Rui B.B. et al. (2016) Di(2-ethylhexyl) phthalate exacerbates non-alcoholic fatty liver in rats and its potential mechanisms. Environ. Toxicol. Pharmacol., 42: 38–44.
• Chen X., Wang J. Qin Q. et al. (2012) Mono-2-ethylhexyl phthalate induced loss of mitochondrial membrane potential and activation of Caspase3 in HepG2 cells. Environ. Toxicol. Pharmacol., 33(3): 421–430.
• Cobellis L., Latini G., DeFelice C. et al. (2003) High plasma concentrations of di-(2-ethylhexyl)-phthalate in women with endometriosis. Human Reprod., 18(7): 1512–1515.
• Craig Z.R., Hannon P.R., Wang W. et al. (2013) Di-n-Butyl phthalate disrupts the expression of genes involved in cell cycle and apoptotic pathways in mouse ovarian antral follicles. Biol. Reprod., 88(1): 23.
• Daniel M., Peek G.W., Tollefsbol T.O. (2012) Regulation of the human catalytic subunit of telomerase (hTERT). Gene, 49: 135–146.
• DeKeyser J.G., Stagliano M.C., Auerbach S.S. et al. (2009) Di(2-ethylhexyl) phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant CAR2. Mol. Pharmacol., 75(5): 1005–1013.
• Desdoits-Lethimonier C., Albert O., Le B.B. et al. (2012) Human testis steroidogenesis is inhibited by phthalates. Human Reprod., 27(5): 1451–1459.
• Deutschle T., Reiter R., Butte W. et al. (2014) A controlled challenge study on di(2-ethylhexyl) phthalate (DEHP) in house dust and the immune response in human nasal mucosa of allergic subjects. Е Health Perspect., 116(11): 1487–1493.
• Doull J., Cattley R., Elcombe C. et al. (1999) A cancerriskassessmentof di(2-ethylhexyl)phthalate: application of the new U.S. EPA riskassessment guidelines. Regul. Toxicol. Pharmacol., 29(3): 327–357.
• Duty S.M., Calafat A.M., Silva M.J. et al. (2005) Phthalate exposure and reproductive hormones in adult men. Human Reprod., 20(3): 604–610.
• Ejaredar M., Nyanza E.C., Ten E.K., Dewey D. (2015) Phthalate exposure and childrens neurodevelopment: a systematic review. Environ. Res., 142: 51–60.
• Ema M., Miyawaki E., Hirose A., Kamata E. (2003) Decreased anogenital distance and increased incidence of undescended testes in fetuses of rats given monobenzyl phthalate, a major metabolite of butyl benzyl phthalate. Reprod. Toxicol., 17(4): 407–412.
• Eurocases (2004) Commission Directive 2004/93/EC of 21 September 2004 amending Council Directive 76/768/EEC for the purpose of adapting its Annexes II and III to technical progress (http://freecases.eu/Doc/LegalAct/3679431).
• European Chemicals Agency (2013) General report (https://echa.europa.eu/documents/10162/13560/mb_04_2014_general_report_2013_en.pdf/e9ac1c75-3655-47db-a29e-e21b1351a0f1).
• European Parliament and of the Council (2014) Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC (Text with EEA relevance) (http://eur-lex.europa.eu/legal-content/HR/%20TXT/?uri=CELEX%3A02006R1907-20140410).
• Ferguson K.K., Cantonwine D.E., Rivera-González L.O. et al. (2014) Urinary phthalate metabolite associations with biomarkers of inflammation and oxidative stress across pregnancy in puerto rico. Environ. Sci. Technol., 48(12): 7018–7025.
• Ferguson K.K., Loch-Caruso R., Meeker J.D. (2012) Exploration of oxidative stress and inflammatory markers in relation to urinaryphthalate metabolites: NHANES 1999–2006. Environ. Sci. Technol., 46(1): 477–485.
• Fourth National Report on Human Exposure to Environmental Chemicals (2015) (https://www.cdc.gov/biomonitoring/pdf/fourthreport_updatedtables_feb2015.pdf).
• Fromme H., Bolte G., Koch H.M. 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.
• Giam C.S., Chan H.S., Neff G.S., Atlas E.L. (1978) Phthalate Ester plasticizers: a new class of marine pollutant. Science, 199(4327): 419–421.
• Goodman M., Lakind J.S., Mattison D.R. (2014) Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature. Crit. Rev. Toxicol., 44(2): 151–175.
• Gray L.E., Ostby J., Furr J. et al. (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(2): 350–365.
• Guidance for Industry Limiting the Use of Certain Phthalates as Excipients in CDER-Regulated Products (2012) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) (https://www.fda.gov/downloads/%20Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM294086.pdf).
• Hagmar L., Akesson B., Nielsen J. et al. (1990) Mortality and cancer morbidity in workers exposed to low levels of vinyl chloride monomer at a polyvinyl chloride processing plant. Am. J. Ind. Med., 17: 553–565.
• Hannon P.R., Flaws J.A. (2015) The effects of phthalates on theovary. Front Endocrinol., 6(8): 1–19.
• Hannon P.R., Peretz J., Flaws J.A. (2014) Daily exposure to Di(2-ethylhexyl) phthalate alters estrous cyclicity and accelerates primordial follicle recruitment potentially via dysregulation of the phosphatidylinositol 3-kinase signaling pathway in adult mice. Biol. Reprod., 90(6): 136.
• Hardell L., Ohlson C.G., Fredrikson M. (1997) Occupational exposure to polyvinyl chloride as a risk factor for testicular cancer evaluated in a case-control study. J. Cancer, 73(6): 828–830.
• Harley K.G., Berger K., Rauch S. et al. (2017) Association of prenatal urinary phthalate metabolite concentrations and childhood BMI and obesity. Pediatr. Res., 82(3): 405–415.
• Hart R., Doherty D.A., Frederiksen H. et al. (2014) The influence of antenatal exposure to phthalates on subsequent female reproductive development in adolescence: a pilot study. Reproduc., 147(4): 379–390.
• Hauser R., Calafat A.M. (2005) Phthalates and human health. Occup. Environ. Med., 62(11): 806–818.
• Heineman E.F., Olsen J.H., Pottern L.M. et al. (1992) Occupational risk factors for multiple myeloma among Danish men. Cancer Causes Control, 3(6): 555–568.
• Hernandez-Diaz S., Mitchell A.A., Kelley K.E. et al. (2009) Medicationsas a potential source of exposure to phthalates in the U.S. population. Environ. Health Perspect., 117(2): 185–189.
• Hernandez-Diaz S., Su Y.C., Mitchell A.A. et al. (2013) Medications as a potential source of exposure to phthalates among women of childbearing age. Reprod. Toxicol., 37: 1–5.
• Heudorf U., Mersch-Sundermann V., Angerer J. (2007) Phthalates: toxicology and exposure. Int. J. Hyg. Environ. Health, 210(5): 623–634.
• Högberg J., Hanberg A., Berglund M. et al. (2008) Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ. Health Perspect., 116(3): 334–339.
• Holahan M.R., Smith C.A. (2015) Phthalates and neurotoxic effects on hippocampal network plasticity. Neurotoxicol., 48: 21–34.
• Hsieh T.H., Tsai C.F., Hsu C.Y. et al. (2012) Phthalates induce proliferation and invasiveness of estrogen receptor-negative breast cancer through the AhR/HDAC6/c-myc signaling pathway. FASEB J., 26: 778–787.
• Hsu Y.L., Hsieh C.J., Tsai E.M. et al. (2016) Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment. Oncol. Lett., 11(2): 1035–1042.
• Huang H.B., Pan W.H., Chang J.W. et al. (2017) Does exposure to phthalates influence thyroid function and growth hormone homeostasis? The Taiwan Environmental Survey for Toxicants (TEST) 2013. Environ. Res., 153: 63–72.
• Huang P.C., Tsai C.H., Liang W.Y. et al. (2016) Early Phthalates exposure in pregnant women is associated with alteration of thyroid hormones. PLoS One, 11(7): 1–18.
• Ichimura T., Kawamura M., Mitani A. (2003) Co-localized expression of FasL, Fas, Caspase-3 and apoptotic DNA fragmentation in mouse testis after oral exposure to di(2-ethylhexyl)phthalate. Toxicol., 194(1–2): 35–42.
• Jaakkola J.J.K., Verkasalo P.K., Jaakkola N. (2000) Plastic wall materials in the home and respiratory health in young children. Am. J. Public Health, 90(5): 797–799.
• James-Todd T.M., Huang T., Seely E.W., Saxena A.R. (2016a) The association between phthalates and metabolic syndrome: the National Health and Nutrition Examination Survey 2001–2010. Environ. Health., 15: 52.
• James-Todd T.M., Meeker J.D., Huang T. et al. (2016b) Pregnancy urinary phthalate metabolite concentrations and gestational diabetes risk factors. Environ. Int., 96: 118–126.
• Johns L.E., Cooper G.S., Galizia A., Meeker J.D. (2015) Exposure assessment issues in epidemiology studies of phthalates. Environ. Int., 85: 27–39.
• Jönsson B.A., Richthoff J., Rylander L. et al. (2005) Urinary phthalate metabolites and biomarkers of reproductive function in young men. Epidemiol., 16: 487–493.
• Jugan M.L., Levi Y., Blondeau J.P. (2010) Endocrine disruptors and thyroid hormone physiology. Biochem. Pharmacol., 79(7): 939–947.
• 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.
• Kang S.C., Lee B.M. (2005) DNA methylation of estrogen receptor alpha gene by phthalates. Toxicol. Environ. Health., 68(23–24): 1995–2003.
• Kavlock R., Boekelheide K., Chapin R. et al. (2002) 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(5): 529–653.
• Keller B.O., Davidson A.G., Innis S.M. (2009) Phthalate metabolites in urine of CF patients are associated with use of enteric-coated pancreatic enzymes. Environ. Toxicol. Pharmacol., 27(3): 424–427.
• Kelley K.E., Hernández-Díaz S. et al. (2012) Identification of phthalates in medications and dietary supplement formulations in the United States and Canada. Environ. Health Perspectm, 120: 379–384.
• Keresztes S., Tatár E., Czégény Z., Záray G., Mihucz V.G. (2013) Study on the leaching of phthalates from polyethylene terephthalate bottles into mineral water. Sci. Total. Environ., 458–460: 451–458.
• Klöting N., Hesselbarth N., Gericke M. et al. (2015) Di-(2-Ethylhexyl)-Phthalate (DEHP) Causes Impaired Adipocyte Function and Alters Serum Metabolites. PLoS One, 10(12): 1–19.
• Koch H.M., Calafat A.M. (2009) Human body burdens of chemicalused in plastic manufacture. Philos. Trans. R. Soc. Lond. B. Biol. Sci., 364(1526): 2063–2078.
• Koch H.M., Drexler H., Angerer J. (2003) An estimation of the daily intake of di (2-ethylhexyl) phthalate (DEHP) and other phthalates in the general population. Int. J. Hyg. Environ. Health, 206(2): 77–83.
• Kolarik B., Naydenov K., Larsson M. et al. (2008) The association between phthalates in dust and allergic diseases among Bulgarian children. Environ. Health Perspect., 116(1): 98–103.
• Krüger T., Long M., Bonefeld-Jørgensen E.C. (2008) Plastic components affect the activation of the aryl hydrocarbon and the androgen receptor. Toxicol., 246(2–3): 112–123.
• Lahousse S.A., Wallace D.G., Liu D. et al. (2006) Testicular gene expression profiling following prepubertal rat mono-(2-ethylhexyl)phthalate exposure suggests a common initial genetic response at fetal and prepubertal ages. Toxicol. Sci., 93(2): 369–381.
• Latini G., De Felice C., Presta G. et al. (2003) In utero exposure to di-(2-ethylhexyl) phthalate and duration of human pregnancy. Environ. Health Perspect., 111: 1783–1785.
• Li L.H., Jester W.F., Laslett A.L., Orth J.M. (2000) A single dose of di-(2-ethylhexyl) phthalate in neonatal rats alters gonocytes, reduces Sertoli cell proliferation, and decreases cyclin D2 expression. Toxicol. Appl. Pharmacol., 166(6): 222–229.
• Lodge C.J., Dharmage S.C. (2016) Breastfeeding and perinatal exposure, and the risk of asthma and allergies. Curr. Opin. Allergy Clin. Immunol, 16(3): 232–236.
• Lopez-Carrillo L., Hernandez-Ramirez R.U., Calafat A.M. et al. (2010) Exposure to phthalates and breast cancer risk in northern Mexico. Environ. Health Perspect., 118(4): 539–544.
• Lovekamp T.N., Davis B.J. (2001) Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells. Toxicol. Appl. Pharmacol., 172(3): 217–224.
• Mackintosh C.E., Maldonado J., Hongwu J. (2004) Distribution Of Phthalate Estersin a marineaquaticfoodweb: comparison polychlorinated biphenyls. Environ. Sci. Technol., 38(7): 2011–2020.
• Mangala Priya V., Mayilvanan C., Akilavalli N. et al. (2014) Lactational exposure of phthalate impairs insulin signaling in the cardiac muscle of F1 female albinorats. Toxicol., 14(1): 10–20.
• Martine B., Marie-Jeanne T., Cendrine D. et al. (2013) Assessment of adult human exposure tophthalateestersintheurban centre of Paris. Bull. Environ. Contam. Toxicol., 90(1): 91–96.
• Mayer F.L., Stalling D.L., Johnson J.L. (1972) Phthalate Esters As Environmental Contaminants. Nature, 238(5364): 411–413.
• Messerlian C., Wylie B.J., Minguez-Alarcon L. et al. (2016) Urinary concentrations of phthalate metabolites and pregnancy loss among women conceiving with medically assisted reproduction. Epidemiol., 27(6): 879–888.
• Muczynski V., Lecureuil C., Messiaen S. et al. (2012) Cellular and molecular effect of MEHP Involving LXRα in human fetal testis and ovary. PLoS One, 7: e48266.
• Mylchreest E., Wallace D.G., Cattley R.C., Foster P.M. (2000) Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to di(n-butyl)phthalate during late gestation. Toxicol. Sci., 55(1): 143–151.
• Official Journal of the European Communities Decision 198/815/EU (1999) European Commission: European Union Scientific Committee on Toxicology, Ecotoxicology, and the Environment.
• Ormond G., Nieuwenhuijsen M.J., Nelson P. et al. (2009) Endocrine disruptors in the workplace, hair spray, folate supplementation, and risk of hypospadias: case-control study. Environ. Health Perspect., 117: 303–307.
• Parks L.G., Ostby J.S., Lambright C.R. et al. (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol. Sci., 58(2): 339–349.
• Percy Z., Xu Y., Sucharew H. et al. (2016) Gestational exposure to phthalates and gender-related play behaviors in 8-year-old children: an observational study. Environ. Health, 15(1): 87.
• Polanska K., Ligocka D., Sobala W., Hanke W. (2014) Effect of environmental phthalate exposure on pregnancy duration and birth outcomes. Int. J. Occup. Med. Environ. Health, 29(4): 683–697.
• Ponsonby A.L., Symeonides C., Vuillermin P. et al. (2016) Epigenetic regulation of neurodevelopmental genes in response to in uteroexposure to phthalate plastic chemicals: How can we delineate causal effects? Neurotoxicol., 55: 92–101.
• Rajesh P., Balasubramanian K. (2014) Phthalate exposure in utero causes epigenetic changes and impairs insulin signalling. J. Endocrinol., 223(1): 47–66.
• Ren P., Zhang Y., Huang Y. et al. (2015) Functions of peroxisome proliferator-activated receptor gamma (PPARγ) in gynecologic disorders. Clin. Med. Insights. Oncol., 9: 43–49.
• Reynolds P., Urayama K.Y., Von Behren J., Feusner J. (2004) Birth characteristics and hepatoblastoma risk in young children. Cancer, 101(1): 206–210.
• Rhodes C., Orton T.C., Pratt I.S. et al. (1986) Comparative pharmacokinetics and subacute toxicity of di(2-ethylhexyl) phthalate (DEHP) in rats and marmosets: extrapolation of effects in rodents to man. Environ. Mental Health Perspectives., 65: 299–307.
• Rouiller-Fabre V., Guerquin M.J., N’Tumba-Byn T. et al. (2015) Nuclear Receptors and Endocrine Disruptors in Fetal and Neonatal Testes: A Gapped Landscape. Front Endocrinol. (Lausanne), 6(58): 1–13.
• Rowe R.C., Sheskey P.J., Quinn M. (2006) Handbook of pharmaceutical excipients with CD-ROM/Book Package Hardcover. McGraw-Hill Medical, 5 Ed., 850 p.
• Rozati R., Reddy P.P., Reddanna P., Mujtaba,R. (2002) Role of environmental estrogens in the deterioration of male factor fertility. Fertil. Steril., 76(6): 1187–1194.
• Rusyn I., Corton J.C. (2012) Mechanistic considerations for human relevance of cancer hazard of di(2-ethylhexyl) phthalate. Mutat. Res., 750(2): 141–158.
• Sears J.K., Darby J.R. (1982) TheTechnology of Plasticizers. Wiley, Hoboken NJ, 1180 p.
• Seckin E., Fromme H., Völkel W. (2009) Determination of total and free mono-n-butyl phthalate in human urine samples after medication of a di-n-butyl phthalate containing capsule. Toxicol. Lett., 188: 33–37.
• Selenskas S., Teta M.J., Vitale J.N. (1995) Pancreatic cancer among workers processing synthetic resins. Am. J. Ind. Med., 28: 385–398.
• Shaban Z., El-Shazly S., Ishizuka M. et al. (2004) PPARalpha-dependent modulation of hepatic CYP1A by clofibric acid in rats. Arch. Toxicol., 78(9): 496–507.
• Silva M.J., Barr D.B., Reidy J.A. 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: 331–338.
• Sjoberg P., Lindqvist N.G., Ploen L. (1986) Age-dependent response of the rat testes to di(2-ethylhexyl) phthalate. Environ. Health Perspect, 65: 237–242.
• Solomon O., Yousefi P., Huen K. et al. (2017) Prenatal phthalate exposure and altered patterns of DNA methylation in cord blood. Environ. Mol. Mutagen, 58(6): 398–410.
• Suzuki Y., Yoshinaga J., Mizumoto Y. et al. (2012) Foetal exposure to phthalate esters and anogenital distance in male newborns. Int. J. Androl., 35: 236–244.
• Swan S.H. (2008) Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ. Res., 108: 177–184.
• Swan S.H., Liu F., Hines M. et al. (2010) Prenatal phthalate exposure and reduced masculine play in boys. Int. J. Androl., 33(2): 259–269.
• Swan S.H., Main K.M., Liu F. et al. (2005) Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure. Environ. Health Perspect, 113(8): 1056–1061.
• Tabacova S.L.R., Balabaeva L. (1999) Maternal exposure to phthalates and complications of pregnancy. Epidemiol. (Suppl. 10): S127.
• Takeshita A., Inagaki K., Igarashi-Migitaka J. et al. (2006) The endocrine disrupting chemical, diethylhexyl phthalate, activates MDR1 gene expression in human colon cancer LS174T cells. J. Endocrinol., 190(3): 897–902.
• Tan G.H. (1995) Residue level soft phthalate esters in water and sediment samples from the Klang River basin. Bull. Environ. Contam. Toxicol., 54(2): 171–176.
• Thurston S.W., Mendiola J., Bellamy A.R. et al. (2016) Phthalate exposure and semen quality in fertile US men. Andrology, 4(4): 632–638.
• Toppari J., Skakkebaek N.E. (1998) Sexual differentiation and environmental endocrine disrupters. Baillieres Clin. Endocrinol. Metab., 12(1): 143–156.
• Voskoboinik I., Ooi S.G., Drew R., Ahokas J.T. (1997) Peroxisome proliferators increase the formation of BPDE-DNA adducts in isolated rat hepatocytes. Toxicol., 122(1–2): 81–91.
• Wang X.K., Agarwal M., Parobchak N. et al. (2016) Mono-(2-Ethylhexyl) phthalate promotes pro-labor gene expression in the human placenta. PLoS One, 11(1): 1–12.
• Wargo J., Cullen M.R., Taylor H.S. (2008) Plastics that may be Harmful to Children and Reproductive Health (http://www.ehhi.org/ehhi_plastics_report_2008.pdf).
• Weuve J., Hauser R., Calafat A.M. et al. (2010) Association of exposure to phthalates with endometriosis and uterine leiomyomata: findings from NHANES, 1999–2004. Environ. Health Perspect., 118(6): 825–832.
• Weuve J., Sanchez B.N., Calafat A.M. et al. (2006) Exposure to phthalates inneonatalintensivecareunitinfants: urinary concentrations of monsters andoxidative metabolites . Environ. Health Perspect., 114(9): 1424–1431.
• Whyatt R.M., Liu X., Rauh V.A. et al. (2012) Maternal prenatal urinary phthalate metabolite concentrations and child mental, psychomotor, and behavioral development at 3 years of age. Health Perspect, 120(2): 290–295.
• Wilkes Ch.E., Summers J.W., Daniels Ch.A. (Eds.) (2005) PVC Handbook. Hanser Publishers, Munich, 723 p.
• Wirth J.J., Rossano M.G., Potter R. et al. (2008) A pilot study associating urinary concentrations of phthalate metabolites and semen quality. Syst. Biol. Reprod. Med., 54: 143–154.
• Wittassek M., Koch H.M., Angerer J., Bruning T. (2011) Assessing exposure to phthalates — the human biomonitoring approach. Mol. Nutr. Food. Res., 55(1): 7–31.
• Wu W., Zhou F., Wang Y. et al. (2017) Phthalate levels and related factors in children aged 6–12 years. Environ. Pollut., 220(Pt. B): 990–996.
• Yang G., Zhou X., Wang J. et al. (2012) MEHP-induced oxidative DNA damage and apoptosis in HepG2 cells correlates with p53-mediated mitochondria-dependent signaling pathway. Food Chem. Toxicol., 50(7): 2424–2431.
• Yao P.L., Lin Y.C., Richburg J.H. (2012) Mono-(2-ethylhexyl) phthalate (MEHP) promotes invasion and migration of human testicular embryonal carcinoma cells. Biol. Reprod., 86(5): 1–10.
• Yun Z., Min C. (2008) U.S. Congress enacted the Consumer Product Safety Improvement Act. (http://www.cpsc.gov/cpsia.pdf).
• Zarean M., Keikha M., Poursafa P. et al. (2016) A systematic review on the adverse health effects of di-2-ethylhexyl phthalate. Environ. Sci. Pollut. Res. Int., 23(24): 24642–24693.
• Zhang S., Ma J., Fu Z. et al. (2016) Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression. Environ. Sci. Pollut. Res. Int., 23(10): 9742–9749.
• Zhao Y., Chen J., Wang X. et al. (2016) Third trimester phthalate exposure is associated with DNA methylation of growth-related genes in human placenta. Sci. Rep., 6(33449): 1–8.
• Zong T., Lai L., Hu J. et al. (2015) Maternal exposure to di-(2-ethylhexyl) phthalate disrupts placental growth and development in pregnant mice. Hazard Mater., 297: 25–33.