Endocrine disrupting potential of replacement flame retardants - Review of current knowledge for nuclear receptors associated with reproductive outcomes

Lola Bajard; Chander K Negi; Vicente Mustieles; Lisa Melymuk; Stéphane Jomini; Johanna Barthelemy-Berneron; Mariana F Fernandez; Ludek Blaha

doi:10.1016/j.envint.2021.106550

Endocrine disrupting potential of replacement flame retardants - Review of current knowledge for nuclear receptors associated with reproductive outcomes

Environ Int. 2021 Aug:153:106550. doi: 10.1016/j.envint.2021.106550. Epub 2021 Apr 10.

Authors

Lola Bajard¹, Chander K Negi¹, Vicente Mustieles², Lisa Melymuk¹, Stéphane Jomini³, Johanna Barthelemy-Berneron³, Mariana F Fernandez², Ludek Blaha⁴

Affiliations

¹ Masaryk University, Faculty of Science, RECETOX, Kamenice 5, CZ62500 Brno, Czechia.
² University of Granada, Center for Biomedical Research (CIBM), Granada, Spain; Ciber de Epidemiologia y Salud Publica (CIBERESP), Madrid, Spain; Instituto de Investigacion Biosanitaria de Granada (ibs. GRANADA), Granada, Spain.
³ ANSES, Agence Nationale de Sécurité Sanitaire de l'alimentation, de l'environnement et du travail, Direction de l'Evaluation des Risques, Unité Evaluation des Substances Chimiques, 14 rue Pierre Marie Curie. 94701 Maisons-Alfort Cedex, France.
⁴ Masaryk University, Faculty of Science, RECETOX, Kamenice 5, CZ62500 Brno, Czechia. Electronic address: ludek.blaha@recetox.muni.cz.

PMID: 33848905
DOI: 10.1016/j.envint.2021.106550

Abstract

Background and aim: Endocrine disrupting chemicals (EDCs) constitute a major public health concern because they can induce a large spectrum of adverse effects by interfering with the hormonal system. Rapid identification of potential EDCs using in vitro screenings is therefore critical, particularly for chemicals of emerging concerns such as replacement flame retardants (FRs). The review aimed at identifying (1) data gaps and research needs regarding endocrine disrupting (ED) properties of replacement FRs and (2) potential EDCs among these emerging chemicals.

Methods: A systematic search was performed from open literature and ToxCast/Tox21 programs, and results from in vitro tests on the activities of 52 replacement FRs towards five hormone nuclear receptors (NRs) associated with reproductive outcomes (estrogen, androgen, glucocorticoid, progesterone, and aryl hydrocarbon receptors) were compiled and organized into tables. Findings were complemented with information from structure-based in silico model predictions and in vivo information when relevant.

Results: For the majority of the 52 replacement FRs, experimental in vitro data on activities towards these five NRs were either incomplete (15 FRs) or not found (24 FRs). Within the replacement FRs for which effect data were found, some appeared as candidate EDCs, such as triphenyl phosphate (TPhP) and tris(1,3-dichloropropyl)phosphate (TDCIPP). The search also revealed shared ED profiles. For example, anti-androgenic activity was reported for 19 FRs and predicted for another 21 FRs.

Discussion: This comprehensive review points to critical gaps in knowledge on ED potential for many replacement FRs, including chemicals to which the general population is likely exposed. Although this review does not cover all possible characteristics of ED, it allowed the identification of potential EDCs associated with reproductive outcomes, calling for deeper evaluation and possibly future regulation of these chemicals. By identifying shared ED profiles, this work also raises concerns for mixture effects since the population is co-exposed to several FRs and other chemicals.

Keywords: Emerging contaminants; Endocrine disruption; Flame retardants; Nuclear receptors; Steroid hormones; ToxCast.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Endocrine Disruptors* / toxicity
Flame Retardants* / toxicity
Humans
Phosphates
Receptors, Cytoplasmic and Nuclear
Reproduction

Substances

Endocrine Disruptors
Flame Retardants
Phosphates
Receptors, Cytoplasmic and Nuclear