Comparison of Endocrine Activity of Phthalates and Alternative Plasticizers

Overview

Journal J Toxicol

Publisher Wiley

Specialty Toxicology

Date 2021 Feb 25

PMID 33628236

Citations 10

Authors

Helene Moche

Aouatif Chentouf

Sergio Neves

Jean-Marc Corpart

Fabrice Nesslany

Affiliations

Soon will be listed here.

Abstract

Because of the deleterious effects of phthalates, regulations have been taken to decrease their use, and the needs for alternatives are increasing. Due to the concerns about the endocrine-disrupting properties of phthalates, it was deemed necessary to particularly investigate these effects for potential substitutes. In this study, we compared the endocrine activity of several already used potential alternative plasticizers (DEHT, DINCH, and TOTM) or new substitutes (POLYSORB® isosorbide and POLYSORB® ID 46) to one of 2 phthalates, DEHP and DINP. Effects of these chemicals on 3 common mechanisms of endocrine disruption, i.e., interaction with estrogen receptors (ER), androgen receptors (AR), or steroidogenesis, were studied using extensively used methods. In the E-Screen assay, only DEHP moderately induced MCF-7 cell proliferation; none of the other tested substances were estrogenic or antiestrogenic. No androgenic or antiandrogenic activity in MDA-kb2 cells was shown for any of the tested phthalates or alternatives. On the other hand, both DEHP and DINP, as well as DEHT, DINCH, and TOTM, disrupted steroidogenesis in the H295R assay, mainly by inducing an increase in estradiol synthesis; no such effect was observed for POLYSORB® isosorbide and POLYSORB® ID 46.

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References

Heudorf U, Mersch-Sundermann V, Angerer J . Phthalates: toxicology and exposure. Int J Hyg Environ Health. 2007; 210(5):623-34. DOI: 10.1016/j.ijheh.2007.07.011. View

Erythropel H, Maric M, Nicell J, Leask R, Yargeau V . Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposure. Appl Microbiol Biotechnol. 2014; 98(24):9967-81. DOI: 10.1007/s00253-014-6183-8. View

Hollert H, Giesy J . The OECD Validation Program of the H295R Steroidogenesis Assay for the Identification of In Vitro Inhibitors and Inducers of Testosterone and Estradiol Production. Phase 2: Inter-Laboratory Pre-Validation Studies (8 pp). Environ Sci Pollut Res Int. 2011; 14 Suppl 1:23-30. DOI: 10.1065/espr2007.03.402. View

Ventrice P, Ventrice D, Russo E, De Sarro G . Phthalates: European regulation, chemistry, pharmacokinetic and related toxicity. Environ Toxicol Pharmacol. 2013; 36(1):88-96. DOI: 10.1016/j.etap.2013.03.014. View

Bui T, Giovanoulis G, Palm Cousins A, Magner J, Cousins I, de Wit C . Human exposure, hazard and risk of alternative plasticizers to phthalate esters. Sci Total Environ. 2015; 541:451-467. DOI: 10.1016/j.scitotenv.2015.09.036. View

Mankidy R, Wiseman S, Ma H, Giesy J . Biological impact of phthalates. Toxicol Lett. 2012; 217(1):50-8. DOI: 10.1016/j.toxlet.2012.11.025. View

Hecker M, Newsted J, Murphy M, Higley E, Jones P, Wu R . Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: hormone production. Toxicol Appl Pharmacol. 2006; 217(1):114-24. DOI: 10.1016/j.taap.2006.07.007. View

Boisvert A, Jones S, Issop L, Erythropel H, Papadopoulos V, Culty M . In vitro functional screening as a means to identify new plasticizers devoid of reproductive toxicity. Environ Res. 2016; 150:496-512. DOI: 10.1016/j.envres.2016.06.033. View

Das M, Kumar M, Thakur I . Differential toxicological endpoints of di(2-ethylhexyl) phthalate (DEHP) exposure in MCF-7 and MDA-MB-231 cell lines: possible estrogen receptor alpha (ERalpha) independent modulations. Indian J Exp Biol. 2014; 52(11):1052-61. View

10.

Shen O, Du G, Sun H, Wu W, Jiang Y, Song L . Comparison of in vitro hormone activities of selected phthalates using reporter gene assays. Toxicol Lett. 2009; 191(1):9-14. DOI: 10.1016/j.toxlet.2009.07.019. View

11.

Desdoits-Lethimonier C, Albert O, Le Bizec B, Perdu E, Zalko D, Courant F . Human testis steroidogenesis is inhibited by phthalates. Hum Reprod. 2012; 27(5):1451-9. DOI: 10.1093/humrep/des069. View

12.

Korner W, Hanf V, Schuller W, Kempter C, Metzger J, Hagenmaier H . Development of a sensitive E-screen assay for quantitative analysis of estrogenic activity in municipal sewage plant effluents. Sci Total Environ. 1999; 225(1-2):33-48. DOI: 10.1016/s0048-9697(99)80015-1. View

13.

Katsikantami I, Sifakis S, Tzatzarakis M, Vakonaki E, Kalantzi O, Tsatsakis A . A global assessment of phthalates burden and related links to health effects. Environ Int. 2016; 97:212-236. DOI: 10.1016/j.envint.2016.09.013. View

14.

Engel A, Buhrke T, Imber F, Jessel S, Seidel A, Volkel W . Agonistic and antagonistic effects of phthalates and their urinary metabolites on the steroid hormone receptors ERα, ERβ, and AR. Toxicol Lett. 2017; 277:54-63. DOI: 10.1016/j.toxlet.2017.05.028. View

15.

Kruger T, Long M, Bonefeld-Jorgensen E . Plastic components affect the activation of the aryl hydrocarbon and the androgen receptor. Toxicology. 2008; 246(2-3):112-23. DOI: 10.1016/j.tox.2007.12.028. View

16.

Araki N, Ohno K, Takeyoshi M, Iida M . Evaluation of a rapid in vitro androgen receptor transcriptional activation assay using AR-EcoScreen cells. Toxicol In Vitro. 2005; 19(3):335-52. DOI: 10.1016/j.tiv.2004.10.008. View

17.

Martinez-Arguelles D, Campioli E, Culty M, Zirkin B, Papadopoulos V . Fetal origin of endocrine dysfunction in the adult: the phthalate model. J Steroid Biochem Mol Biol. 2013; 137:5-17. DOI: 10.1016/j.jsbmb.2013.01.007. View

18.

Wilson V, Bobseine K, Lambright C, Gray Jr L . A novel cell line, MDA-kb2, that stably expresses an androgen- and glucocorticoid-responsive reporter for the detection of hormone receptor agonists and antagonists. Toxicol Sci. 2002; 66(1):69-81. DOI: 10.1093/toxsci/66.1.69. View

19.

Roy P, Salminen H, Koskimies P, Simola J, Smeds A, Saukko P . Screening of some anti-androgenic endocrine disruptors using a recombinant cell-based in vitro bioassay. J Steroid Biochem Mol Biol. 2004; 88(2):157-66. DOI: 10.1016/j.jsbmb.2003.11.005. View

20.

Engel A, Buhrke T, Kasper S, Behr A, Braeuning A, Jessel S . The urinary metabolites of DINCH have an impact on the activities of the human nuclear receptors ERα, ERβ, AR, PPARα and PPARγ. Toxicol Lett. 2018; 287:83-91. DOI: 10.1016/j.toxlet.2018.02.006. View