Comparison of In Vitro Endocrine Activity of Phthalates and Alternative Plasticizers.

Hélène Moche,Aouatif Chentouf,Fabrice Nesslany,Jean-Marc Corpart,Sergio Neves,You-Cheng Hseu

doi:10.1155/2021/8815202

Hélène Moche, Aouatif Chentouf + Show 4 more

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https://doi.org/10.1155/2021/8815202

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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 in vitro 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 in vitro 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.

Highlights

Phthalates or phthalic acid esters are a family of synthetic organic chemicals that are mainly used as plasticizers in the polymer industry. ey are notably used for the manufacture of polyvinylchloride (PVC), making it flexible and processable
Following the recent publication of an Journal of Toxicology amendment to Annex XVII [11], the same restrictions will apply to diisobutyl phthalate (DIBP) after July 2020, and these 4 phthalates will be restricted in plasticized materials in a wider array of products. ereby, DEHP, dibutyl phthalate (DBP), benzyl butyl phthalate (BBP), and DIBP are restricted in the insulation of electrical cables and wires in the RoHS (Restriction of Hazardous Substances) directive
DEHP was the only compound inducing a significant increase in MCF-7 cell proliferation compared to the solvent control in the agonist E-Screen assay (Figure 1(a)). is statistically significant increase was, moderate, with a maximum proliferative effect of 5.25 at the DEHP concentration of 3.10−5 M, corresponding to about 30% of the proliferative effect induced by estradiol

Summary

Introduction

Phthalates or phthalic acid esters are a family of synthetic organic chemicals that are mainly used as plasticizers in the polymer industry. ey are notably used for the manufacture of polyvinylchloride (PVC), making it flexible and processable. Four phthalates are included in Annex XIV of the European Regulation on Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) listing the substances of very high concern requiring authorization before use and are classified as toxic for reproduction (category 1B): benzyl butyl phthalate (BBP), DEHP, DBP, and diisobutyl phthalate (DIBP). In Europe, some phthalates are restricted for use in toys and childcare articles in the REACH Regulation (Annex XVII): DEHP, DBP, and BBP. Some restrictions on the use of phthalates in materials in contact with foodstuffs are defined by Directive 2007/19/EC: a ban on DIBP, specific migration limits for food for DEHP, DBP, BBP, and (together with other substances) DIDP and DINP. Some phthalates (e.g., DBP, BBP, and DEHP) are prohibited in cosmetic products [13]

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