Plasticisers: A Potential Reproductive-toxicant for Humans

  • Abhisikta Mandal Integrative Biology Research Unit (IBRU), Department of Life Sciences, Presidency University, Kolkata, West Bengal, India.
  • Anshumi Banerjee Integrative Biology Research Unit (IBRU), Department of Life Sciences, Presidency University, Kolkata, West Bengal, India.
  • Manashi Debnath Office of the Chief Medical Officer of Health, Tamluk, Purba Medinipur, West Bengal, India.
  • Kousik Pramanick Integrative Biology Research Unit (IBRU), Department of Life Sciences, Presidency University, Kolkata, West Bengal, India. https://orcid.org/0000-0003-1822-4646
Keywords: Plasticiser, Bisphenol A, Phthalates, Reproductive Toxicity

Abstract

The advancement in science and technology has led to the discovery and formulations of various cheaper alternatives to our day to day commodities. Plastic is one of them. Plasticisers include a group of chemicals that increase the flexibility of plastics so that they can be moulded into the forms of our use. The plasticisers have led to a number of health hazards when they leach out into the environment. This review is going to be a comparative discussion, on the effects of different plasticisers on human health, and the main focus on plasticiser-induced reproductive toxicity. This study revealed that there are anomalies in the male reproductive system like cryptorchidism, hypospadias acrosomal dysgenesis, prostate cancer, and testicular cancer. Reduced fertility, deterioration in sperm quality, drop in testosterone synthesis, and reduced anogenital distance reveal the feminising effects of phthalates. Mono phthalates are the metabolites of these chemicals and cause similar effects. Bisphenol A (BPA) also has similar endocrine-disrupting potential. DNA damage has been recorded in sperms along with disruption in the secretion of the follicle-stimulating hormone and plasma and intratesticular testosterone. Both spermatogenesis and spermiogenesis were highly affected due to exposure to these chemicals. Females exposed to plasticisers show oocyte incompetence, increased possibility of miscarriage, polycystic ovarian syndrome, and disrupted secretion of oestrogen and progesterone leading to ovulatory cycles. Abnormalities in oogenesis occur during the meiotic phases.

How to cite this article:
Mandal A, Banerjee A, Debnath M, Pramanick K. Plasticisers: A Potential Reproductive-toxicant for Humans. Chettinad Health City Med J. 2022;54(1):29-37.

DOI: https://doi.org/10.24321/2278.2044.202206

References

Daniels PH. A brief overview of theories of PVC plasticization and methods used to evaluate PVCâ€plasticizer interaction. J Vinyl Addit Tech. 2009;15(4):219-23. [Google Scholar]

Gibbons WS, Kusy RP. Influence of plasticizer configurational changes on the mechanical properties of highly plasticized poly (vinyl chloride). Polymer. 1998;39(26):6755-65. [Google Scholar]

Goulas AE, Anifantaki KI, Kolioulis DG, Kontominas MG. Migration of di-(2-ethylhexylexyl) adipate plasticizer from food-grade polyvinyl chloride film into hard and soft cheeses. J Dairy Sci. 2000;83(8):1712-8. [PubMed] [Google Scholar]

Dupont LA, Gupta VP. Degradative transesterification of terephthalate polyesters to obtain DOTP plasticizer for flexible PVC. J Vinyl Tech. 1993;15(2):100-4. [Google Scholar]

Begley TH, Hollifield HC. Migration of dibenzoate plasticizers and polyethylene terephthalate cyclic oligomers from microwave susceptor packaging into food-simulating liquids and food. J Food Prot. 1990;53(12):1062-6. [PubMed] [Google Scholar]

Svoboda RD. Polymeric plasticizers for higher performance flexible PVC applications. J Vinyl Tech. 1991;13(3):130-3. [Google Scholar]

Graham PR. Phthalate ester plasticizers--why and how they are used. Environ Health Perspect. 1973;3:3-12. [PubMed] [Google Scholar]

Nieschlag HJ, Tallent WH, Wolff IA. Simplified preparation of a diester plasticizer from crambe seed oil. Ind Engi Chem Prod Res Dev. 1969;8(2):216. [Google Scholar]

Nara K, Nishiyama K, Natsugari H, Takeshita A, Takahashi H. Leaching of the plasticizer, acetyl tributyl citrate: (ATBC) from plastic kitchen wrap. J Health Sci. 2009;55(2):281-4. [Google Scholar]

Mathieu-Denoncourt J, Wallace SJ, de Solla SR, Langlois VS. Plasticizer endocrine disruption: highlighting developmental and reproductive effects in mammals and non-mammalian aquatic species. Gen Comp Endocrinol. 2015;219:74-88. [PubMed] [Google Scholar]

Fong RJ, Robertson A, Mallon PE, Thompson RL. The impact of plasticizer and degree of hydrolysis on free volume of poly (vinyl alcohol) films. Polymers. 2018;10(9):1036. [PubMed] [Google Scholar]

Kavlock R, Boekelheide K, Chapin R, Cunningham M, Faustman E, Foster P, Golub M, Henderson R, Hinberg I, Little R, Seed J, Shea K, Tabacova S, Tyl R, Williams P, Zacharewski T. 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. 2002;16(5):529-653. [PubMed] [Google Scholar]

Zhang Y, Jiang X, Chen B. Reproductive and developmental toxicity in F1 Sprague Dawley male rats exposed to di-n-butyl phthalate in utero and during lactation and determination of its NOAEL. Reprod Toxicol. 2004;18(5):669-76. [PubMed] [Google Scholar]

Mose T, Mortensen GK, Hedegaard M, Knudsen LE. Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood. Reprod Toxicol. 2007;23(1):83-91. [PubMed] [Google Scholar]

Venkata NG, Robinson JA, Cabot PJ, Davis B, Monteith GR, Roberts-Thomson SJ. Mono (2-ethylhexyl) phthalate and mono-n-butyl phthalate activation of peroxisome proliferator activated-receptors α and γ in breast. Toxicol Lett. 2006;163(3):224-34. [PubMed] [Google Scholar]

Kay VR, Chambers C, Foster WG. Reproductive and developmental effects of phthalate diesters in females. Crit Rev Toxicol. 2013;43(3):200-19. [PubMed] [Google Scholar]

Euling SY, White LD, Kim AS, Sen B, Wilson VS, Keshava C, Keshava N, Hester S, Ovacik MA, Ierapetritou MG, Androulakis IP, Gaido KW. Use of genomic data in risk assessment case study: II. Evaluation of the dibutyl phthalate toxicogenomic data set. Toxicol Appl Pharmacol. 2013;271(3):349-62. [PubMed] [Google Scholar]

Toner F, Allan G, Dimond SS, Waechter Jr JM, Beyer D. In vitro percutaneous absorption and metabolism of Bisphenol A (BPA) through fresh human skin. Toxicol In Vitro. 2018;47:147-55. [PubMed] [Google Scholar]

Zalko D, Jacques C, Duplan H, Bruel S, Perdu E. Viable skin efficiently absorbs and metabolizes bisphenol A. Chemosphere. 2011;82(3):424-30. [PubMed] [Google Scholar]

Loganathan SN, Kannan K. Occurrence of bisphenol A in indoor dust from two locations in the eastern United States and implications for human exposures. Arch Environ Contam Toxicol. 2011;61(1):68-73. [PubMed] [Google Scholar]

Fan J, Traore K, Li W, Amri H, Huang H, Wu C, Chen H, Zirkin B, Papadopoulos V. Molecular mechanisms mediating the effect of mono-(2-ethylhexyl) phthalate on hormone-stimulated steroidogenesis in MA-10 mouse tumor Leydig cells. Endocrinology. 2010;151(7):3348-62. [PubMed] [Google Scholar]

Pant N, Pant A, Shukla M, Mathur N, Gupta Y, Saxena D. Environmental and experimental exposure of phthalate esters: the toxicological consequence on human sperm. Hum Exp Toxicol. 2011;30(6):507-14. [PubMed] [Google Scholar]

Suzuki Y, Yoshinaga J, Mizumoto Y, Serizawa S, Shiraishi H. Foetal exposure to phthalate esters and anogenital distance in male newborns. Int J Androl. 2012;35(3):236-44. [PubMed] [Google Scholar]

Benson R. Hazard to the developing male reproductive system from cumulative exposure to phthalate esters dibutyl phthalate, diisobutyl phthalate, butylbenzyl phthalate, diethylhexyl phthalate, dipentyl phthalate, and diisononyl phthalate. Regul Toxicol Pharmacol. 2009;53(2):90-101. [PubMed] [Google Scholar]

Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R, Prins GS, Soto AM, Zoeller RT, Gore AC. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009;30(4):293-342. [PubMed] [Google Scholar]

Machtinger R, Orvieto R. Bisphenol A, oocyte maturation, implantation, and IVF outcome: review of animal and human data. Reprod Biomed Online. 2014;29(4):404-10. [PubMed] [Google Scholar]

Meeker JD, Sathyanarayana S, Swan SH. Phthalates and other additives in plastics: human exposure and associated health outcomes. Philos Trans R Soc B Biol Sci. 2009;364(1526):2097-113. [PubMed] [Google Scholar]

Martinoâ€Andrade AJ, Chahoud I. Reproductive toxicity of phthalate esters. Mol Nutr Food Res. 2010;54(1):148-57. [PubMed] [Google Scholar]

Foster PM, Cattley RC, Mylchreest E. Effects of di-n-butyl phthalate (DBP) on male reproductive development in the rat: implications for human risk assessment. Food Chem Toxicol. 2000;38:S97-9. [PubMed] [Google Scholar]

Swan SH. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environ Res. 2008;108(2):177-84. [PubMed] [Google Scholar]

Sunman B, Yurdakök K, Kocer-Gumusel B, Özyüncü Ö, Akbıyık F, Balcı A, Özkemahlı G, Erkekoğlu P, Yurdakök M. Prenatal bisphenol a and phthalate exposure are risk factors for male reproductive system development and cord blood sex hormone levels. Reprod Toxicol. 2019;87:146-55. [PubMed] [Google Scholar]

Sharma P, Roy S, Karimiâ€Varzaneh HA. Impact of plasticizer addition on molecular properties of polybutadiene rubber and its manifestations to glass transition temperature. Macromol Theory Sim. 2019;28(4):1900003. [Google Scholar]

Stachowiak N, Kowalonek J, Kozlowska J. Effect of plasticizer and surfactant on the properties of poly (vinyl alcohol)/chitosan films. Int J Biol Macromol. 2020;164:2100-7. [PubMed] [Google Scholar]

Lagos-Cabré R, Moreno RD. Contribution of environmental pollutants to male infertily: a working model of germ cell apoptosis induced by plasticizers. Biol Res. 2012;45(1):5-14. [PubMed] [Google Scholar]

Chen G, Li Y, Wang J. Occurrence and ecological impact of microplastics in aquaculture ecosystems. Chemosphere. 2021;274:129989. [PubMed] [Google Scholar]

Ghisari M, Bonefeld-Jorgensen EC. Effects of plasticizers and their mixtures on estrogen receptor and thyroid hormone functions. Toxicol Lett. 2009;189(1):67-77. [PubMed] [Google Scholar]

Liang X, Yang R, Yin N, Faiola F. Evaluation of the effects of low nanomolar bisphenol A-like compounds’ levels on early human embryonic development and lipid metabolism with human embryonic stem cell in vitro differentiation models. J Hazard Mater. 2021;407:124387. [PubMed] [Google Scholar]

Kumar N, Srivastava S, Roy P. Impact of low molecular weight phthalates in inducing reproductive malfunctions in male mice: special emphasis on Sertoli cell functions. Gen Comp Endocrinol. 2015;215:36-50. [Google Scholar]

Huang YQ, Wong CK, Zheng JS, Bouwman H, Barra R, Wahlström B, Neretin L, Wong MH. Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts. Environ Int. 2012;42:91-9. [PubMed] [Google Scholar]

Krzastek SC, Farhi J, Gray M, Smith RP. Impact of environmental toxin exposure on male fertility potential. Transl Androl Urol. 2020;9(6):2797. [PubMed] [Google Scholar]

Akingbemi BT, Ge R, Klinefelter GR, Zirkin BR, Hardy MP. Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc Natl Acad Sci USA. 2004;101(3):775-80. [PubMed] [Google Scholar]

Erkekoglu P, Zeybek ND, Giray B, Asan E, Arnaud J, Hincal F. Reproductive toxicity of di (2-ethylhexyl) phthalate in selenium-supplemented and selenium-deficient rats. Drug Chem Toxicol. 2011;34(4):379-89. [PubMed] [Google Scholar]

Tian Y, Zhou X, Miao M, Li DK, Wang Z, Li R, Liang H, Yuan W. Association of bisphenol A exposure with LINE-1 hydroxymethylation in human semen. Int J Environ Res Public Health. 2018;15(8):1770. [PubMed] [Google Scholar]

Desdoits-Lethimonier C, Lesné L, Gaudriault P, Zalko D, Antignac JP, Deceuninck Y, Platel C, Dejucq-Rainsford N, Mazaud-Guittot S, Jégou B. Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis. Hum Reprod. 2017;32(7):1465-73. [PubMed] [Google Scholar]

Mansur A, Adir M, Yerushalmi G, Hourvitz A, Gitman H, Yung Y, Orvieto R, Machtinger R. Does BPA alter steroid hormone synthesis in human granulosa cells in vitro? Hum Reprod. 2016;31(7):1562-9. [PubMed] [Google Scholar]

Varghese AC, Ly KD, Corbin C, Mendiola J, Agarwal A. Oocyte developmental competence and embryo development: impact of lifestyle and environmental risk factors. Reprod Biomed Online. 2011;22(5):410-20. [PubMed] [Google Scholar]

Elmetwally MA, Halawa AA, Lenis YY, Tang W, Wu G, Bazer FW. Effects of BPA on expression of apoptotic genes and migration of ovine trophectoderm (oTr1) cells during the peri-implantation period of pregnancy. Reprod Toxicol. 2019;83:73-9. [PubMed] [Google Scholar]

Benachour N, Aris A. Toxic effects of low doses of Bisphenol-A on human placental cells. Toxicol Appl Pharmacol. 2009;241(3):322-8. [PubMed] [Google Scholar]

de Aguiar Greca SC, Kyrou I, Pink R, Randeva H, Grammatopoulos D, Silva E, Karteris E. Involvement of the endocrine-disrupting chemical bisphenol A (BPA) in human placentation. J Clin Med. 2020;9(2):405. [PubMed] [Google Scholar]

Yang YJ, Hong YC, Oh SY, Park MS, Kim H, Leem JH, Ha EH. Bisphenol A exposure is associated with oxidative stress and inflammation in postmenopausal women. Environ Res. 2009;109(6):797-801. [PubMed] [Google Scholar]

Huang M, Liu S, Fu L, Jiang X, Yang M. Bisphenol A and its analogues bisphenol S, bisphenol F and bisphenol AF induce oxidative stress and biomacromolecular damage in human granulosa KGN cells. Chemosphere. 2020;253:126707. [PubMed] [Google Scholar]

Ema M, Miyawaki E, Kawashima K. Critical period for adverse effects on development of reproductive system in male offspring of rats given di-n-butyl phthalate during late pregnancy. Toxicol Lett. 2000;111(3):271-8. [PubMed] [Google Scholar]

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(4):505-15. [PubMed] [Google Scholar]

Jobling TR, Reynolds T, White R, Parker MG, Sumpter JP. A variety of environmentally persistent chemicals, including some phtalates plasticizers, are weakly estrogenic. Environ Health Perspect. 1995 Jun;103(6):582-7. [PubMed] [Google Scholar]

Vitku J, Kolatorova L, Franekova L, Blahos J, Simkova M, Duskova M, Skodova T, Starka L. Endocrine disruptors of the bisphenol and paraben families and bone metabolism. Physiol Res. 2018;67:S455-64. [PubMed] [Google Scholar]

Grande SW, Andrade AJ, Talsness CE, Grote K, Chahoud I. A dose-response study following in utero and lactational exposure to di (2-ethylhexyl) phthalate: effects on female rat reproductive development. Toxicol Sci. 2006;91(1):247-54. [PubMed] [Google Scholar]

Howdeshell KL, Furr J, Lambright CR, Rider CV, Wilson VS, Gray Jr LE. Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: altered fetal steroid hormones and genes. Toxicol Sci. 2007;99(1):190-202. [PubMed] [Google Scholar]

Harris CA, Henttu P, Parker MG, Sumpter JP. The estrogenic activity of phthalate esters in vitro. Environ Health Perspect. 1997;105(8):802-11. [PubMed] [Google Scholar]

Li Y. Life cycle assessment to di-2-ethylhexyl phthalate (DEHP), applications and potential alternatives [dissertation]. University of Pittsburgh; 2013. [Google Scholar]

Schütze A, Gries W, Kolossa-Gehring M, Apel P, Schröter-Kermani C, Fiddicke U, Leng G, Brüning T, Koch HM. Bis-(2-propylheptyl) phthalate (DPHP) metabolites emerging in 24 h urine samples from the German Environmental Specimen Bank (1999–2012). Int J Hyg Environ Health. 2015;218(6):559-63. [PubMed] [Google Scholar]

Wilkinson CF, Lamb IV JC. The potential health effects of phthalate esters in children’s toys: a review and risk assessment. Regul Toxicol Pharmacol. 1999;30(2):140-55. [PubMed] [Google Scholar]

Koniecki D, Wang R, Moody RP, Zhu J. Phthalates in cosmetic and personal care products: concentrations and possible dermal exposure. Environ Res. 2011;111(3):329-36. [PubMed] [Google Scholar]

Just AC, Miller RL, Perzanowski MS, Rundle AG, Chen Q, Jung KH, Hoepner L, Camann DE, Calafat AM, Perera FP, Whyatt RM. Vinyl flooring in the home is associated with children’s airborne butylbenzyl phthalate and urinary metabolite concentrations. J Expo Sci Environ Epidemiol. 2015;25(6):574-9. [PubMed] [Google Scholar]

Heudorf U, Mersch-Sundermann V, Angerer J. Phthalates: toxicology and exposure. Int J Hyg Environ Health. 2007;210(5):623-34. [PubMed] [Google Scholar]

Wang J, Luo Y, Teng Y, Ma W, Christie P, Li Z. Soil contamination by phthalate esters in Chinese intensive vegetable production systems with different modes of use of plastic film. Environ Pollut. 2013;180:265-73. [PubMed] [Google Scholar]

Krauskopf LG. Plasticizer structure/performance relationships. J Vinyl Tech. 1993;15(3):140-7. [Google Scholar]

Huang PC, Liao KW, Chang JW, Chan SH, Lee CC. Characterization of phthalates exposure and risk for cosmetics and perfume sales clerks. Environ Pollut. 2018;233:577-87. [PubMed] [Google Scholar]

Coltro L, Pitta JB, Madaleno E. Performance evaluation of new plasticizers for stretch PVC films. Polymer Testing. 2013;32(2):272-8. [Google Scholar]

Jahnke GD, Iannucci AR, Scialli AR, Shelby MD. Center for the evaluation of risks to human reproduction the first five years. Birth Defects Res B Dev Reprod Toxicol. 2005;74(1):1-8. [PubMed] [Google Scholar]

Arzuaga X, Walker T, Yost EE, Radke EG, Hotchkiss AK. Use of the adverse outcome pathway (AOP) framework to evaluate species concordance and human relevance of dibutyl phthalate (DBP)-induced male reproductive toxicity. Reprod Toxicol. 2020;96:445-58. [PubMed] [Google Scholar]

Hart RJ, Frederiksen H, Doherty DA, Keelan JA, Skakkebaek NE, Minaee NS, McLachlan R, Newnham JP, Dickinson JE, Pennell CE, Norman RJ, Main KM. The possible impact of antenatal exposure to ubiquitous phthalates upon male reproductive function at 20 years of age. Front Endocrinol. 2018;9:288. [PubMed] [Google Scholar]

Waring RH, Harris RM. Endocrine disrupters: a human risk? Mol Cell Endocrinol. 2005;244(1-2):2-9. [PubMed] [Google Scholar]

Hu Y, Dong C, Chen M, Lu J, Han X, Qiu L, Chen Y, Qin J, Li X, Gu A, Xia Y, Sun H, Li Z, Wang Y. Low-dose monobutyl phthalate stimulates steroidogenesis through steroidogenic acute regulatory protein regulated by SF-1, GATA-4 and C/EBP-beta in mouse Leydig tumor cells. Reprod Biol Endocrinol. 2013;11(1):72. [PubMed] [Google Scholar]

Latini G, Scoditti E, Verrotti A, De Felice C, Massaro M. Peroxisome proliferator-activated receptors as mediators of phthalate-induced effects in the male and female reproductive tract: epidemiological and experimental evidence. PPAR Res. 2008;2008:359267. [PubMed] [Google Scholar]

Cobellis L, Latini G, Felice CD, Razzi S, Paris I, Ruggieri F, Mazzeo P, Petraglia F. High plasma concentrations of diâ€(2â€ethylhexyl)â€phthalate in women with endometriosis. Hum Reprod. 2003;18(7):1512-5. [PubMed] [Google Scholar]

Rais-Bahrami K, Nunez S, Revenis ME, Luban NL, Short BL. Follow-up study of adolescents exposed to di (2-ethylhexyl) phthalate (DEHP) as neonates on extracorporeal membrane oxygenation (ECMO) support. Environ Health Perspect. 2004;112(13):1339-40. [PubMed] [Google Scholar]

Martinez-Arguelles DB, Campioli E, Culty M, Zirkin BR, Papadopoulos V. Fetal origin of endocrine dysfunction in the adult: the phthalate model. J Steroid Biochem Mol Biol. 2013;137:5-17. [PubMed] [Google Scholar]

Svechnikova I, Svechnikov K, Soder O. The influence of di-(2-ethylhexyl) phthalate on steroidogenesis by the ovarian granulosa cells of immature female rats. J Endocrinol. 2007;194(3):603-9. [PubMed] [Google Scholar]

Ma Y, Zhang J, Zeng R, Qiao X, Cheng R, Nie Y, Luo Y, Li S, Zhang J, Xu W, Xu L, Hu Y. Effects of the dibutyl phthalate (DBP) on the expression and activity of aromatase in human granulosa cell line KGN. Ann Clin Lab Sci. 2019;49(2):175-82. [PubMed] [Google Scholar]

Chang WH, Herianto S, Lee CC, Hung H, Chen HL. The effects of phthalate ester exposure on human health: a review. Sci Total Environ. 2021;786:147371. [PubMed]

Published
2022-03-30