{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T04:30:44Z","timestamp":1769315444639,"version":"3.49.0"},"reference-count":123,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["2020.06616.BD"],"award-info":[{"award-number":["2020.06616.BD"]}]},{"name":"CICS-UBI"},{"name":"CICS-UBI"},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia I.P.","award":["UID\/50017\/2025"],"award-info":[{"award-number":["UID\/50017\/2025"]}]},{"name":"FCT\u2013Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia I.P.","award":["LA\/P\/0094\/2020"],"award-info":[{"award-number":["LA\/P\/0094\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Thyroid hormones (THs) regulate almost all physiological processes in vertebrates via specific mechanisms exercised spatiotemporally throughout the lifespan. The TH signalling can be impaired by thyroid-disrupting chemicals (TDCs) capable of disrupting the hypothalamic\u2013pituitary\u2013thyroid (HPT) axis. Octyl methoxycinnamate (OMC) (also designated octinoxate), one of the most widely used ultraviolet (UV) filters, has emerged as an environmental contaminant and has raised significant concerns recently due to its disruptive effects as TDC on humans and animals. Although the disruption of TH homeostasis has been reported, its exact modes of action (MoA) remain largely unknown. Our study aimed to provide a comparative information on the molecular interactions of OMC on TH signalling in humans and zebrafish. Methods: In silico approaches were performed comparing OMC with endogenous thyroid hormone T3 and the anti-thyroid drug propylthiouracil (PTU). Results: Our findings suggested a key role of OMC on the corticotrophin-releasing hormone receptor (crhr2), thyrotropin receptor (TSHR\/tshr), and thyroid nuclear receptors (TR\/tr-\u03b1 and -\u03b2). At the hypothalamic level, a favourable binding of OMC to zebrafish crhr2 was found, involving ALA86, CYS44, HIS89, ILE63, ILE64, LEU92, PRO87, PRO88, SER48, and THR47. At the pituitary level, OMC was bound to human TSHR by the amino acid residues ASN590, GLU506, ILE583, ILE640, LEU570, MET572, PRO571, SER505, TYR667, VAL502, VAL586, ALA644, LEU587, MET637, SER641, and TYR582 and to zebrafish tsrh by ASN589, ILE639, MET636, ILE582, LEU569, LEU586, VAL501, and VAL585. Concerning nuclear receptors, OMC showed a more favourable binding energy of T3, involving the shared residues PHE218 and MET259 with T3 in both species. For human TR\u03b2, OMC shared T3 with residues ILE 275, ILE276, LEU346, PHE269, PHE272, THR273, ALA279, ASN331, HIS435, LEU330, MET310, MET313, and PHE455. No similar residues were obtained for zebrafish tr\u03b2 compared with the humans. Conclusions: Overall, the action of OMC seems to agree with primary hypothyroidism (anti-thyroid action) mimicking the T3 hormone. This investigation demonstrates that OMC acts as a potential TDC and provides new insights into its disruptive action on the HPT axis.<\/jats:p>","DOI":"10.3390\/ph18121897","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T17:22:58Z","timestamp":1765905778000},"page":"1897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In Silico Identification of Molecular Interactions of the Emerging Contaminant Octyl Methoxycinnamate (OMC) on HPT Axis: Implications for Humans and Zebrafish"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4752-6398","authenticated-orcid":false,"given":"Margarida","family":"Lorigo","sequence":"first","affiliation":[{"name":"FCS-UBI, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"Department of Biology & CESAM (Centre for Environmental and Marine Studies), University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8550-1645","authenticated-orcid":false,"given":"Luiza","family":"Breitenfeld","sequence":"additional","affiliation":[{"name":"FCS-UBI, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1891-7365","authenticated-orcid":false,"given":"Marta S.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Department of Biology & CESAM (Centre for Environmental and Marine Studies), University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-9470","authenticated-orcid":false,"given":"Amadeu M. V. M.","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Biology & CESAM (Centre for Environmental and Marine Studies), University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1151-8177","authenticated-orcid":false,"given":"Carla","family":"Quintaneiro","sequence":"additional","affiliation":[{"name":"Department of Biology & CESAM (Centre for Environmental and Marine Studies), University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4823-5701","authenticated-orcid":false,"given":"Elisa","family":"Cairrao","sequence":"additional","affiliation":[{"name":"FCS-UBI, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"},{"name":"RISE-Health, Department of Medical Sciences, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilh\u00e3, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1152\/physrev.2001.81.3.1097","article-title":"Physiological and molecular basis of thyroid hormone action","volume":"81","author":"Yen","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_2","unstructured":"OECD (2014). New Scoping Document on In Vitro and Ex Vivo Assays for the Identification of Modulators of Thyroid Hormone Signalling, OECD."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"95001","DOI":"10.1289\/EHP5297","article-title":"Evaluating chemicals for thyroid disruption: Opportunities and challenges with in vitro testing and adverse outcome pathway approaches","volume":"127","author":"Noyes","year":"2019","journal-title":"Environ. Health Perspect."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Ramhoj, L., Axelstad, M., Baert, Y., Canas-Portilla, A.I., Chalmel, F., Dahmen, L., De La Vieja, A., Evrard, B., Haigis, A.C., and Hamers, T. (2023). New approach methods to improve human health risk assessment of thyroid hormone system disruption-a parc project. Front. Toxicol., 5.","DOI":"10.3389\/ftox.2023.1189303"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.tox.2016.01.009","article-title":"The application of molecular modelling in the safety assessment of chemicals: A case study on ligand-dependent ppargamma dysregulation","volume":"392","author":"Tsakovska","year":"2017","journal-title":"Toxicology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105391","DOI":"10.1016\/j.yrtph.2023.105391","article-title":"Identification of molecular initiating events (mie) using chemical database analysis and nuclear receptor activity assays for screening potential inhalation toxicants","volume":"141","author":"Jeong","year":"2023","journal-title":"Regul. Toxicol. Pharmacol. RTP"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1002\/etc.5584","article-title":"New approach methodologies for the endocrine activity toolbox: Environmental assessment for fish and amphibians","volume":"42","author":"Mitchell","year":"2023","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1002\/etc.5878","article-title":"Development of a zebrafish embryo-based test system for thyroid hormone system disruption: 3rs in ecotoxicological research","volume":"44","author":"Golz","year":"2024","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1038\/nature12111","article-title":"The zebrafish reference genome sequence and its relationship to the human genome","volume":"496","author":"Howe","year":"2013","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.cbpc.2018.06.005","article-title":"Zebrafish (Danio rerio): A valuable tool for predicting the metabolism of xenobiotics in humans?","volume":"212","author":"Sardela","year":"2018","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.reprotox.2014.09.005","article-title":"Comparison of toxicity values across zebrafish early life stages and mammalian studies: Implications for chemical testing","volume":"55","author":"Ducharme","year":"2015","journal-title":"Reprod. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/sj.clpt.6100223","article-title":"Zebrafish: An emerging model system for human disease and drug discovery","volume":"82","author":"Kari","year":"2007","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"114836","DOI":"10.1016\/j.envres.2022.114836","article-title":"Binding of common organic uv-filters to the thyroid hormone transport protein transthyretin using in vitro and in silico studies: Potential implications in health","volume":"217","author":"Cotrina","year":"2023","journal-title":"Environ. Res."},{"key":"ref_14","first-page":"157","article-title":"Update about the effects of the sunscreen ingredients oxybenzone and octinoxate on humans and the environment","volume":"39","author":"Siller","year":"2019","journal-title":"Plast. Surg. Nurs. Off. J. Am. Soc. Plast. Reconstr. Surg. Nurses"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/jat.4210","article-title":"Ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane: Toxicological effects on marine biota and human concerns","volume":"42","author":"Santos","year":"2022","journal-title":"J. Appl. Toxicol. JAT"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.ijwd.2020.08.008","article-title":"Sunscreens: Uv filters to protect us: Part 2-increasing awareness of uv filters and their potential toxicities to us and our environment","volume":"7","author":"Fivenson","year":"2021","journal-title":"Int. J. Womens Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"142218","DOI":"10.1016\/j.chemosphere.2024.142218","article-title":"Exposure to uv-b filter octylmethoxycinnamate and human health effects: Focus on endocrine disruptor actions","volume":"358","author":"Lorigo","year":"2024","journal-title":"Chemosphere"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1080\/10937404.2023.2296897","article-title":"Effects associated with exposure to the emerging contaminant octyl-methoxycinnamate (a uv-b filter) in the aquatic environment: A review","volume":"27","author":"Lorigo","year":"2024","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1289\/ehp.9369","article-title":"Endocrine disruptors and the thyroid gland\u2014A combined in vitro and in vivo analysis of potential new biomarkers","volume":"115","author":"Schmutzler","year":"2007","journal-title":"Environ. Health Perspect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s00204-013-1018-4","article-title":"Monitoring of deiodinase deficiency based on transcriptomic responses in sh-sy5y cells","volume":"87","author":"Song","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lorigo, M., Quintaneiro, C., Breitenfeld, L., and Cairrao, E. (2021). Uv-b filter octylmethoxycinnamate alters the vascular contractility patterns in pregnant women with hypothyroidism. Biomedicines, 9.","DOI":"10.3390\/biomedicines9020115"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"128176","DOI":"10.1016\/j.chemosphere.2020.128176","article-title":"Effects of 2-ethylhexyl-4-methoxycinnamate (ehmc) on thyroid hormones and genes associated with thyroid, neurotoxic, and nephrotoxic responses in adult and larval zebrafish (Danio rerio)","volume":"263","author":"Chu","year":"2021","journal-title":"Chemosphere"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1007\/s10646-022-02555-1","article-title":"Waterborne exposure to avobenzone and octinoxate induces thyroid endocrine disruption in wild-type and thralphaa(-\/-) zebrafish larvae","volume":"31","author":"Ka","year":"2022","journal-title":"Ecotoxicology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109030","DOI":"10.1016\/j.envint.2024.109030","article-title":"Thyroid, neurodevelopmental, and kidney toxicities of common organic uv filters in embryo-larval zebrafish (Danio rerio), and their potential links","volume":"192","author":"Jo","year":"2024","journal-title":"Environ. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1016\/j.talanta.2011.07.085","article-title":"Rapid and selective determination of uv filters in seawater by liquid chromatography-tandem mass spectrometry combined with stir bar sorptive extraction","volume":"85","author":"Nguyen","year":"2011","journal-title":"Talanta"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1021\/es040055r","article-title":"Occurrence of some organic uv filters in wastewater, in surface waters, and in fish from swiss lakes","volume":"39","author":"Balmer","year":"2005","journal-title":"Environ. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/j.envpol.2009.11.005","article-title":"Widespread occurrence of estrogenic uv-filters in aquatic ecosystems in Switzerland","volume":"158","author":"Fent","year":"2010","journal-title":"Environ. Pollut."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1007\/s00216-011-5560-8","article-title":"Analysis of uv filters in tap water and other clean waters in Spain","volume":"402","author":"Llorca","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"142486","DOI":"10.1016\/j.scitotenv.2020.142486","article-title":"Risks of organic uv filters: A review of environmental and human health concern studies","volume":"755","author":"Huang","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/j.1468-3083.2007.02492.x","article-title":"Sunscreens in human plasma and urine after repeated whole-body topical application","volume":"22","author":"Janjua","year":"2008","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/j.chemosphere.2010.09.079","article-title":"Exposure patterns of uv filters, fragrances, parabens, phthalates, organochlor pesticides, pbdes, and pcbs in human milk: Correlation of uv filters with use of cosmetics","volume":"81","author":"Schlumpf","year":"2010","journal-title":"Chemosphere"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1002\/jat.3621","article-title":"Measurement of concentrations of four chemical ultraviolet filters in human breast tissue at serial locations across the breast","volume":"38","author":"Barr","year":"2018","journal-title":"J. Appl. Toxicol. JAT"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139883","DOI":"10.1016\/j.chemosphere.2023.139883","article-title":"Exploring environmental obesogenous effects of organic ultraviolet filters on children from a case-control study","volume":"341","author":"Wang","year":"2023","journal-title":"Chemosphere"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.envint.2015.03.012","article-title":"Environmental occurrence and risk of organic uv filters and stabilizers in multiple matrices in Norway","volume":"80","author":"Langford","year":"2015","journal-title":"Environ. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.envpol.2015.09.039","article-title":"Toxic heritage: Maternal transfer of pyrethroid insecticides and sunscreen agents in dolphins from Brazil","volume":"207","author":"Alonso","year":"2015","journal-title":"Environ. Pollut."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"143914","DOI":"10.1016\/j.scitotenv.2020.143914","article-title":"Toxicogenomic fin(ger)prints for thyroid disruption aop refinement and biomarker identification in zebrafish embryos","volume":"760","author":"Reinwald","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref_37","unstructured":"OECD (2018). Revised Guidance Document 150 on Standardised Test Guidelines for Evaluating Chemicals for Endocrine Disruption, OECD."},{"key":"ref_38","unstructured":"OECD (2019). Tg 248: Xenopus Eleutheroembryonic Thyroid Assay (XETA), OECD."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"303","DOI":"10.14573\/altex.1402011","article-title":"Developmental toxicity of thyroid-active compounds in a zebrafish embryotoxicity test","volume":"31","author":"Jomaa","year":"2014","journal-title":"Altex"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neuro.2019.05.008","article-title":"Changes in thyroid hormone activity disrupt photomotor behavior of larval zebrafish","volume":"74","author":"Walter","year":"2019","journal-title":"Neurotoxicology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1177\/1093526620908984","article-title":"Thyroid hormone in the pathogenesis of congenital intestinal dysganglionosis","volume":"23","author":"Wang","year":"2020","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1210\/en.2016-1935","article-title":"Low thyroid hormone levels disrupt thyrotrope development","volume":"158","author":"Tonyushkina","year":"2017","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.ygcen.2005.10.014","article-title":"Role of corticotropin-releasing hormone as a thyrotropin-releasing factor in non-mammalian vertebrates","volume":"146","author":"Darras","year":"2006","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.mce.2017.07.038","article-title":"Frontiers in endocrine disruption: Impacts of organotin on the hypothalamus-pituitary-thyroid axis","volume":"460","author":"Andrade","year":"2018","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_45","first-page":"261","article-title":"Corticotropin-releasing hormone family and their receptors in the cardiovascular system","volume":"83","author":"Takefuji","year":"2019","journal-title":"Circ. J. Off. J. Jpn. Circ. Soc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20240069","DOI":"10.1515\/chem-2024-0069","article-title":"Homology modeling and molecular docking study of corticotrophin-releasing hormone: An approach to treat stress-related diseases","volume":"22","author":"Ahmad","year":"2024","journal-title":"Open Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.3116669","article-title":"Thyroid hormone regulates trh biosynthesis in the paraventricular nucleus of the rat hypothalamus","volume":"238","author":"Segerson","year":"1987","journal-title":"Science"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.ygcen.2008.12.010","article-title":"Thyrotropin in teleost fish","volume":"161","author":"MacKenzie","year":"2009","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2900","DOI":"10.1016\/S0021-9258(18)89450-9","article-title":"Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone","volume":"260","author":"Shupnik","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41421-022-00477-0","article-title":"Molecular basis for the activation of thyrotropin-releasing hormone receptor","volume":"8","author":"Ji","year":"2022","journal-title":"Cell Discov."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.jes.2024.05.027","article-title":"Comparative assessment of thyroid disrupting effects of ethiprole and its metabolites: In silico, in vitro, and in vivo study","volume":"155","author":"Song","year":"2025","journal-title":"J. Environ. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113175","DOI":"10.1016\/j.envres.2022.113175","article-title":"Application of machine learning to predict the inhibitory activity of organic chemicals on thyroid stimulating hormone receptor","volume":"212","author":"Xu","year":"2022","journal-title":"Environ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11984","DOI":"10.1021\/acs.est.6b02771","article-title":"Structure-based virtual screening protocol for in silico identification of potential thyroid disrupting chemicals targeting transthyretin","volume":"50","author":"Zhang","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0074-7696(07)58003-4","article-title":"Cell and molecular biology of transthyretin and thyroid hormones","volume":"258","author":"Richardson","year":"2007","journal-title":"Int. Rev. Cytol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"138273","DOI":"10.1016\/j.chemosphere.2023.138273","article-title":"Adverse thyroid hormone and behavioral alterations induced by three frequently used synthetic musk compounds in embryo-larval zebrafish (Danio rerio)","volume":"324","author":"Chae","year":"2023","journal-title":"Chemosphere"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"159074","DOI":"10.1016\/j.scitotenv.2022.159074","article-title":"Octinoxate as a potential thyroid hormone disruptor\u2014A combination of in vivo and in vitro data","volume":"856","author":"Cahova","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"466","DOI":"10.5603\/EP.a2020.0052","article-title":"Thyroid gland dysfunction and its effect on the cardiovascular system: A comprehensive review of the literature","volume":"71","author":"Ahmadi","year":"2020","journal-title":"Endokrynol. Pol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41572-022-00357-7","article-title":"Hypothyroidism","volume":"8","author":"Chaker","year":"2022","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Sheikh, I.A., Beg, M.A., Hamoda, T.A.A., Mandourah, H.M.S., and Memili, E. (2023). An analysis of the structural relationship between thyroid hormone-signaling disruption and polybrominated diphenyl ethers: Potential implications for male infertility. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043296"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zughaibi, T.A., Sheikh, I.A., and Beg, M.A. (2022). Insights into the endocrine disrupting activity of emerging non-phthalate alternate plasticizers against thyroid hormone receptor: A structural perspective. Toxics, 10.","DOI":"10.3390\/toxics10050263"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1177\/0748233720928165","article-title":"Endocrine disruption: Molecular interactions of environmental bisphenol contaminants with thyroid hormone receptor and thyroxine-binding globulin","volume":"36","author":"Beg","year":"2020","journal-title":"Toxicol. Ind. Health"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"13264","DOI":"10.1021\/acs.est.2c05328","article-title":"Azole-induced color vision deficiency associated with thyroid hormone signaling: An integrated in vivo, in vitro, and in silico study","volume":"56","author":"Chen","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1021\/acs.est.1c06562","article-title":"Assessment of thyroid endocrine disruption effects of parabens using in vivo, in vitro, and in silico approaches","volume":"56","author":"Liang","year":"2022","journal-title":"Environ. Sci. Technol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"136855","DOI":"10.1016\/j.jhazmat.2024.136855","article-title":"Exposure to oxygenated polycyclic aromatic hydrocarbons and endocrine dysfunction: Multi-level study based on hormone receptor responses","volume":"485","author":"Ren","year":"2025","journal-title":"J. Hazard. Mater."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e22814","DOI":"10.1002\/jbt.22814","article-title":"Syringic acid, a novel thyroid hormone receptor-beta agonist, ameliorates propylthiouracil-induced thyroid toxicity in rats","volume":"35","author":"Panda","year":"2021","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"123242","DOI":"10.1016\/j.envpol.2023.123242","article-title":"Insights into spirotetramat-induced thyroid disruption during zebrafish (Danio rerio) larval development: An integrated approach with in vivo, in vitro, and in silico analyses","volume":"343","author":"Jiao","year":"2024","journal-title":"Environ. Pollut."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"97009","DOI":"10.1289\/EHP5314","article-title":"Limited chemical structural diversity found to modulate thyroid hormone receptor in the tox21 chemical library","volume":"127","author":"Martin","year":"2019","journal-title":"Environ. Health Perspect."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16552","DOI":"10.1021\/acs.est.1c04997","article-title":"Structures of endocrine-disrupting chemicals correlate with the activation of 12 classic nuclear receptors","volume":"55","author":"Tan","year":"2021","journal-title":"Environ. Sci. Technol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ren, B., and Zhu, Y. (2022). A new perspective on thyroid hormones: Crosstalk with reproductive hormones in females. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052708"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1055\/a-1716-7980","article-title":"What is the role of thyroid hormone receptor alpha 2 (tralpha2) in human physiology?","volume":"130","author":"Paisdzior","year":"2022","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"9460","DOI":"10.1021\/acs.est.8b02418","article-title":"Joint effects of multiple uv filters on zebrafish embryo development","volume":"52","author":"Li","year":"2018","journal-title":"Environ. Sci. Technol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.aquatox.2015.12.015","article-title":"Thyroid disruption in zebrafish (Danio rerio) larvae: Different molecular response patterns lead to impaired eye development and visual functions","volume":"172","author":"Baumann","year":"2016","journal-title":"Aquat. Toxicol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Baumann, L., Segner, H., Ros, A., Knapen, D., and Vergauwen, L. (2019). Thyroid hormone disruptors interfere with molecular pathways of eye development and function in zebrafish. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071543"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ygcen.2018.11.007","article-title":"Effects of thyroid hormone disruption on the ontogenetic expression of thyroid hormone signaling genes in developing zebrafish (Danio rerio)","volume":"272","author":"Walter","year":"2019","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1002\/etc.5608","article-title":"Reversibility of thyroid hormone system-disrupting effects on eye and thyroid follicle development in zebrafish (Danio rerio) embryos","volume":"42","author":"Pannetier","year":"2023","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"33711","DOI":"10.1007\/s11356-022-24531-2","article-title":"Developmental exposure to triclosan and benzophenone-2 causes morphological alterations in zebrafish (Danio rerio) thyroid follicles and eyes","volume":"30","author":"Kraft","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aquatox.2018.04.009","article-title":"An aop-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish","volume":"200","author":"Stinckens","year":"2018","journal-title":"Aquat. Toxicol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"117374","DOI":"10.1016\/j.envpol.2021.117374","article-title":"Fish toxicity testing for identification of thyroid disrupting chemicals","volume":"284","author":"Dang","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.scitotenv.2018.11.071","article-title":"Effects of 25 thyroid hormone disruptors on zebrafish embryos: A literature review of potential biomarkers","volume":"656","author":"Spaan","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/nrcardio.2016.174","article-title":"Thyroid hormones and cardiovascular disease","volume":"14","author":"Jabbar","year":"2017","journal-title":"Nat. reviews. Cardiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"266","DOI":"10.5551\/jat.32755","article-title":"Thyroid hormone and vascular remodeling","volume":"23","author":"Ichiki","year":"2016","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"497","DOI":"10.3390\/jox14020030","article-title":"Exposure to dep modifies the human umbilical artery vascular resistance contributing to hypertension in pregnancy","volume":"14","author":"Mariana","year":"2024","journal-title":"J. Xenobiot."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"115628","DOI":"10.1016\/j.envres.2023.115628","article-title":"Evaluation of the bisphenol a-induced vascular toxicity on human umbilical artery","volume":"226","author":"Fonseca","year":"2023","journal-title":"Environ. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"153158","DOI":"10.1016\/j.tox.2022.153158","article-title":"Pathways involved in the human vascular tetrabromobisphenol a response: Calcium and potassium channels and nitric oxide donors","volume":"470","author":"Feiteiro","year":"2022","journal-title":"Toxicology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1289\/ehp.01109239","article-title":"In vitro and in vivo estrogenicity of uv screens","volume":"109","author":"Schlumpf","year":"2001","journal-title":"Environ. Health Perspect."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Li, Z., Ptak, D., Zhang, L., Walls, E.K., Zhong, W., and Leung, Y.F. (2012). Phenylthiourea specifically reduces zebrafish eye size. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040132"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"110565","DOI":"10.1016\/j.cbi.2023.110565","article-title":"A metabolomics approach to reveal the mechanism of developmental toxicity in zebrafish embryos exposed to 6-propyl-2-thiouracil","volume":"382","author":"Wilhelmi","year":"2023","journal-title":"Chem. Biol. Interact."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"125749","DOI":"10.1016\/j.chemosphere.2019.125749","article-title":"Evaluation of structurally different brominated flame retardants interacting with the transthyretin and their toxicity on hepg2 cells","volume":"246","author":"Chi","year":"2020","journal-title":"Chemosphere"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"106815","DOI":"10.1016\/j.aquatox.2023.106815","article-title":"Bioaccumulation and thyroid endcrione disruption of 2-ethylhexyl diphenyl phosphate at environmental concentration in zebrafish larvae","volume":"267","author":"Shu","year":"2024","journal-title":"Aquat. Toxicol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ygcen.2014.03.015","article-title":"Mechanisms of crosstalk between endocrine systems: Regulation of sex steroid hormone synthesis and action by thyroid hormones","volume":"203","author":"Trudeau","year":"2014","journal-title":"Gen. Comp. Endocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"242","DOI":"10.12688\/openreseurope.18739.1","article-title":"A 2024 inventory of test methods relevant to thyroid hormone system disruption for human health and environmental regulatory hazard assessment","volume":"4","author":"Vergauwen","year":"2024","journal-title":"Open Res. Eur."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.1007\/s00204-017-2020-z","article-title":"Adverse outcome pathways: A concise introduction for toxicologists","volume":"91","author":"Vinken","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"140611","DOI":"10.1016\/j.chemosphere.2023.140611","article-title":"In silico bioavailability triggers applied to direct and indirect thyroid hormone disruptors","volume":"348","author":"Kuhne","year":"2024","journal-title":"Chemosphere"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.csbj.2016.09.001","article-title":"Zebrafish small molecule screens: Taking the phenotypic plunge","volume":"14","author":"Williams","year":"2016","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"122302","DOI":"10.1016\/j.envpol.2023.122302","article-title":"Disrupting effects of the emerging contaminant octylmethoxycinnamate (OMC) on human umbilical artery relaxation","volume":"335","author":"Lorigo","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Lorigo, M., Quintaneiro, C., Breitenfeld, L., and Cairrao, E. (2022). Uv-b filter octylmethoxycinnamate is a modulator of the serotonin and histamine receptors in human umbilical arteries. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051054"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"130302","DOI":"10.1016\/j.chemosphere.2021.130302","article-title":"Uv-b filter octylmethoxycinnamate impaired the main vasorelaxant mechanism of human umbilical artery","volume":"277","author":"Lorigo","year":"2021","journal-title":"Chemosphere"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Lorigo, M., Quintaneiro, C., Lemos, M.C., Martinez-de-Oliveira, J., Breitenfeld, L., and Cairrao, E. (2019). Uv-b Filter octylmethoxycinnamate induces vasorelaxation by Ca(2+) channel inhibition and guanylyl cyclase activation in human umbilical arteries. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061376"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Damiani, E., Sella, F., Astolfi, P., Galeazzi, R., Carnevali, O., and Maradonna, F. (2023). First in vivo insights on the effects of tempol-methoxycinnamate, a new uv filter, as alternative to octyl methoxycinnamate, on zebrafish early development. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076767"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"134546","DOI":"10.1016\/j.scitotenv.2019.134546","article-title":"Comparative toxicity of uv-filter octyl methoxycinnamate and its photoproducts on zebrafish development","volume":"718","author":"Nataraj","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.aquatox.2018.11.001","article-title":"Parental transfer of ethylhexyl methoxy cinnamate and induced biochemical responses in zebra fish","volume":"206","author":"Zhou","year":"2019","journal-title":"Aquat. Toxicol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.reprotox.2019.04.004","article-title":"Heightened susceptibility: A review of how pregnancy and chemical exposures influence maternal health","volume":"92","author":"Varshavsky","year":"2020","journal-title":"Reprod. Toxicol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1007\/BF03401379","article-title":"Sun lotion chemicals as endocrine disruptors","volume":"14","author":"Maipas","year":"2015","journal-title":"Hormones (Athens)"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1111\/j.1365-2605.2012.01280.x","article-title":"Sunscreens: Are they beneficial for health? An overview of endocrine disrupting properties of uv-filters","volume":"35","author":"Krause","year":"2012","journal-title":"Int. J. Androl."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1001\/jama.2019.20747","article-title":"Effect of sunscreen application on plasma concentration of sunscreen active ingredients: A randomized clinical trial","volume":"323","author":"Matta","year":"2020","journal-title":"JAMA"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.taap.2010.10.031","article-title":"Effects of pre- and postnatal exposure to the uv-filter octyl methoxycinnamate (omc) on the reproductive, auditory and neurological development of rat offspring","volume":"250","author":"Axelstad","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1055\/s-2007-1004589","article-title":"Octyl-methoxycinnamate (omc), an ultraviolet (uv) filter, alters lhrh and amino acid neurotransmitters release from hypothalamus of immature rats","volume":"116","author":"Szwarcfarb","year":"2008","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1055\/s-0029-1224153","article-title":"In vitro effect of octyl\u2014Methoxycinnamate (omc) on the release of gn-rh and amino acid neurotransmitters by hypothalamus of adult rats","volume":"118","author":"Carbone","year":"2010","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1210\/en.2014-1504","article-title":"Differential gene expression patterns in developing sexually dimorphic rat brain regions exposed to antiandrogenic, estrogenic, or complex endocrine disruptor mixtures: Glutamatergic synapses as target","volume":"156","author":"Lichtensteiger","year":"2015","journal-title":"Endocrinology"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.chroma.2017.01.041","article-title":"Assessment of parabens and ultraviolet filters in human placenta tissue by ultrasound-assisted extraction and ultra-high performance liquid chromatography-tandem mass spectrometry","volume":"1487","author":"Ballesteros","year":"2017","journal-title":"J. Chromatogr. A"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2533\/chimia.2008.345","article-title":"Endocrine active uv filters:: Developmental toxicity and exposure through breast milk","volume":"62","author":"Schlumpf","year":"2008","journal-title":"Chimia"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.chemosphere.2018.11.096","article-title":"Toxicity effects of the organic uv-filter 4-methylbenzylidene camphor in zebrafish embryos","volume":"218","author":"Quintaneiro","year":"2019","journal-title":"Chemosphere"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"107939","DOI":"10.1016\/j.jsb.2023.107939","article-title":"Revisiting the ramachandran plot based on statistical analysis of static and dynamic characteristics of protein structures","volume":"215","author":"Park","year":"2023","journal-title":"J. Struct. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"W593","DOI":"10.1093\/nar\/gkac389","article-title":"Prankweb 3: Accelerated ligand-binding site predictions for experimental and modelled protein structures","volume":"50","author":"Jakubec","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13321-018-0285-8","article-title":"P2rank: Machine learning based tool for rapid and accurate prediction of ligand binding sites from protein structure","volume":"10","author":"Krivak","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.csbj.2024.03.015","article-title":"Databases of ligand-binding pockets and protein-ligand interactions","volume":"23","author":"Carpenter","year":"2024","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"Autodock vina 1.2.0: New docking methods, expanded force field, and python bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"Autodock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Aulifa, D.L., Amirah, S.R., Rahayu, D., Megantara, S., and Muchtaridi, M. (2024). Pharmacophore modeling and binding affinity of secondary metabolites from angelica keiskei to hmg co-a reductase. Molecules, 29.","DOI":"10.3390\/molecules29132983"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ab.2007.11.027","article-title":"A steady state mathematical model for stepwise \u201cslow-binding\u201d reversible enzyme inhibition","volume":"380","author":"Kuzmic","year":"2008","journal-title":"Anal. Biochem."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.talanta.2013.10.025","article-title":"Analytical aspects of enzyme reversible inhibition","volume":"118","author":"Amine","year":"2014","journal-title":"Talanta"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"E697","DOI":"10.1002\/cpz1.697","article-title":"Uniprot tools: Blast, align, peptide search, and id mapping","volume":"3","author":"Zaru","year":"2023","journal-title":"Curr. Protoc."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1897\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T17:25:13Z","timestamp":1765905913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,16]]},"references-count":123,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ph18121897"],"URL":"https:\/\/doi.org\/10.3390\/ph18121897","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,16]]}}}