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Benzophenone-3: Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies

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dc.contributor.author Mustieles, Vicente
dc.contributor.author Balogh, Ria K.
dc.contributor.author Axelstad, Marta
dc.contributor.author Montazeri, Parisa, 1988-
dc.contributor.author Márquez, Sandra
dc.contributor.author Vrijheid, Martine
dc.contributor.author Draskau, Monica K.
dc.contributor.author Taxvig, Camilla
dc.contributor.author Peinado, Francisco M.
dc.contributor.author Berman, Tamar
dc.contributor.author Frederiksen, Hanne
dc.contributor.author Fernández, Mariana F.
dc.contributor.author Vinggaard, Anne Marie
dc.contributor.author Andersson, Anna-Maria
dc.date.accessioned 2023-03-21T07:18:46Z
dc.date.available 2023-03-21T07:18:46Z
dc.date.issued 2023
dc.identifier.citation Mustieles V, Balogh RK, Axelstad M, Montazeri P, Márquez S, Vrijheid M, Draskau MK, Taxvig C, Peinado FM, Berman T, Frederiksen H, Fernández MF, Marie Vinggaard A, Andersson AM. Benzophenone-3: Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies. Environ Int. 2023 Jan 6;173:107739. DOI: 10.1016/j.envint.2023.107739
dc.identifier.issn 0160-4120
dc.identifier.uri http://hdl.handle.net/10230/56304
dc.description.abstract Background: Benzophenone-3 (BP-3) and its major metabolite benzophenone-1 (BP-1) are widely used as UV filters in sunscreens and cosmetics to prevent sunburn and skin damage, or as stabilizers to prevent photodegradation in many commercial products. As a result, their presence is ubiquitous in the environment, wildlife and humans. Based on endocrine disruption concerns, international regulatory agencies are performing a closer evaluation. Objective and methods: This work aimed to comprehensively review the available human relevant evidence for safety issues in MEDLINE/PubMed in order to create a structured database of studies, as well as to conduct an integrative analysis as part of the Human Biomonitoring for Europe (HBM4EU) Initiative. Results: A total of 1,635 titles and abstracts were screened and 254 references were evaluated and tabulated in detail, and classified in different categories: i) exposure sources and predictors; ii) human biomonitoring (HBM) exposure levels to perform a meta-analysis; iii) toxicokinetic data in both experimental animals and humans; iv) in vitro and in vivo rodent toxicity studies; and v) human data on effect biomarkers and health outcomes. Our integrative analysis showed that internal peak BP-3 concentrations achieved after a single whole-body application of a commercially available sunscreen (4% w/w) may overlap with concentrations eliciting endocrine disrupting effects in vitro, and with internal concentrations causing in vivo adverse female reproductive effects in rodents that were supported by still limited human data. The adverse effects in rodents included prolonged estrous cycle, altered uterine estrogen receptor gene expression, endometrium hyperplasia and altered proliferation and histology of the mammary gland, while human data indicated menstrual cycle hormonal alterations and increased risk of uterine fibroids and endometriosis. Among the modes of action reported (estrogenic, anti-androgenic, thyroid, etc.), BP-3 and especially BP-1 showed estrogenic activity at human-relevant concentrations, in agreement with the observed alterations in female reproductive endpoints. The meta-analysis of HBM studies identified a higher concern for North Americans, showing urinary BP-3 concentrations on average 10 and 20 times higher than European and Asian populations, respectively. Discussion and conclusions: Our work supports that these benzophenones present endocrine disrupting properties, endorsing recent European regulatory efforts to limit human exposure. The reproducible and comprehensive database generated may constitute a point of departure in future risk assessments to support regulatory initiatives. Meanwhile, individuals should not refrain from sunscreen use. Commercially available formulations using inorganic UV filters that are practically not absorbed into systemic circulation may be recommended to susceptible populations.
dc.description.sponsorship This work is a direct product of the Human Biomonitoring for Europe Project (European Union Commission H2020-EJP-HBM4EU Grant agreement No 733032). The funder had no role in the study design, data collection or analysis, decision to publish, or preparation of the manuscript. V. Mustieles and P. Montazeri were under contract within the HBM4EU Initiative.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Environ Int. 2023 Jan 6;173:107739
dc.rights © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Benzophenone-3: Comprehensive review of the toxicological and human evidence with meta-analysis of human biomonitoring studies
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.envint.2023.107739
dc.subject.keyword Benzophenone
dc.subject.keyword Endocrine disruptor
dc.subject.keyword HBM4EU
dc.subject.keyword Oxybenzone
dc.subject.keyword Risk assessment
dc.subject.keyword Sunscreen
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733032
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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