{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:52:29Z","timestamp":1791010349255,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFAA069878"],"award-info":[{"award-number":["2025GXNSFAA069878"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Adolescents are uniquely vulnerable to endocrine\u2010disrupting chemicals (EDCs) due to the critical maturation of the hypothalamic\u2013pituitary\u2013gonadal (HPG) axis, yet current safety assessments overlook whole\u2010formulation risks during this developmental window. Using an adolescent zebrafish model, we established a biologically anchored screening threshold and elucidated the molecular mechanisms of formulation toxicity. Direct exposure to personal care products at unadjusted Scientific Committee on Consumer Safety (SCCS)\u2013derived concentrations caused severe systemic overload (\n                    <jats:italic>F1<\/jats:italic>\n                    survival \u2264\u200916.87%). High\u2010dilution screening of a 17\u03b1\u2010ethinylestradiol (EE2)\u2013spiked model lotion identified a 160\u00d7 SCCS dilution as the no\u2010observed\u2010adverse\u2010effect level (NOAEL) for reproductive and neurodevelopmental endpoints. Ovarian metabolomics revealed a dichotomous threshold response: The 160\u00d7 dilution induced focused, adaptive reprogramming of steroid hormone biosynthesis (modulating methionine, tyrosine, and histidine), whereas the 80\u00d7 dilution triggered an energetic\u2010inflammatory crisis characterized by acylcarnitine accumulation, tricarboxylic acid cycle suppression, and oxidative stress. This metabolic disruption led to hypothalamic AMP\u2010activated protein kinase (AMPK)\u2013mediated gonadotropin suppression and follicular atresia. Although the formulation matrix partially mitigated EE2\u2010induced ovarian failure, it failed to prevent\n                    <jats:italic>F1<\/jats:italic>\n                    neurobehavioral hypoactivity, implicating parallel thyroid and monoaminergic disruption. Commercial sunscreen validation confirmed product\u2010specific hazards at a 40\u00d7 dilution, proving that whole\u2010formulation toxicity cannot be predicted from ingredient lists alone. These findings redefine risk assessment by advocating for whole\u2010formulation, mechanism\u2010informed screening. The 160\u00d7 dilution threshold offers regulators a pragmatic, health\u2010protective benchmark to safeguard adolescent reproductive and neurodevelopmental health through molecular endocrinology\u2013guided toxicology.\n                  <\/jats:p>","DOI":"10.1002\/jat.70466","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:54:48Z","timestamp":1791006888000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Health\u2010Protective Screening Threshold for Personal Care Products: Metabolomic and Endocrine Mechanisms of Adolescent Reproductive Toxicity in Zebrafish"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-9131-3497","authenticated-orcid":false,"given":"Qinqian","family":"Tao","sequence":"first","affiliation":[{"name":"R&amp;D Management Department Guangdong Kangaroo Mommy Group Co. Ltd.  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3733-6446","authenticated-orcid":false,"given":"Yongbin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Science and Environmental Studies and State Key Laboratory of Marine Environmental Health The Education University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmei","family":"Chen","sequence":"additional","affiliation":[{"name":"R&amp;D Management Department Guangdong Kangaroo Mommy Group Co. Ltd.  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8268-1135","authenticated-orcid":false,"given":"Erping","family":"Yan","sequence":"additional","affiliation":[{"name":"R&amp;D Management Department Guangdong Kangaroo Mommy Group Co. Ltd.  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisan","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology Guangxi Normal University  Guilin China"},{"name":"Research Center for Biomedical Sciences Guangxi Normal University  Guilin China"},{"name":"College of Life Sciences Guangxi Normal University  Guilin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8570-0943","authenticated-orcid":false,"given":"Xueping","family":"Chen","sequence":"additional","affiliation":[{"name":"Vitargent (International) Biotechnology Limited  Hong Kong China"},{"name":"Biotest Big Data R&amp;D Centre, Research Institute of Tsinghua, Pearl River Delta  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3585-6645","authenticated-orcid":false,"given":"Jinping","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Science and Environmental Studies and State Key Laboratory of Marine Environmental Health The Education University of Hong Kong  Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2022.113463","article-title":"Exposure to a Mixture of Personal Care Product and Plasticizing Chemicals in Relation to Reproductive Hormones and Menarche Timing Among 12\u201019 Years Old Girls in NHANES 2013\u20102016","volume":"170","author":"Bigambo F. 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