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Pyriproxyfen (PPF), a juvenile hormone analog widely utilized in vector control, is recommended by the World Health Organization (WHO) for application at concentrations of up to 10\u00a0\u00b5g\/L in drinking water; however, its safety profile for vertebrates remains a matter of concern. In this study, we investigated the endocrine and systemic impacts of PPF in adult female zebrafish exposed for 14\u00a0days to 1, 10, or 100\u00a0\u00b5g\/L. Histological, hormonal, and transcriptional analyses across the thyroid, brain, liver, and kidney revealed a non-monotonic response centered on the WHO reference application concentration. The 10\u00a0\u00b5g\/L group exhibited the most significant molecular impairment in the thyroid, characterized by the upregulation of\n                    <jats:italic>slc5a5<\/jats:italic>\n                    (\n                    <jats:italic>nis<\/jats:italic>\n                    ),\n                    <jats:italic>nkx2.1<\/jats:italic>\n                    ,\n                    <jats:italic>pax2a<\/jats:italic>\n                    , and\n                    <jats:italic>tshr<\/jats:italic>\n                    , while repressing thyroglobulin (\n                    <jats:italic>tg)<\/jats:italic>\n                    expression. Consistent with these molecular alterations, thyroid epithelial disruption was observed at 1 and 10\u00a0\u00b5g\/L. In contrast, exposure to 100\u00a0\u00b5g\/L increased plasma TSH levels and the expression of pituitary\n                    <jats:italic>tshb<\/jats:italic>\n                    and hepatic\n                    <jats:italic>dio1,<\/jats:italic>\n                    suggesting a compensatory response of the HPT axis. Renal morphometry additionally revealed tubular alterations across all exposure groups. Overall, these findings demonstrate a non-monotonic concentration\u2013response centered on 10\u00a0\u00b5g\/L as a key mechanistic feature of PPF toxicity and support further evaluation of thyroid and renal endpoints in ecotoxicological risk assessment.\n                  <\/jats:p>","DOI":"10.1007\/s11356-026-38319-1","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T02:08:03Z","timestamp":1792375683000},"page":"17497-17512","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Endocrine and systemic toxicity of pyriproxyfen in adult female zebrafish: disruption of the HPT axis and peripheral organ impairments"],"prefix":"10.1007","volume":"33","author":[{"given":"Andressa Pereira","family":"Cabral","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabricio Pereira","family":"dos Santos Maia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dam\u00e1ris Barcelos Cunha","family":"Azeredo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a Souza","family":"de Jesus Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lycia","family":"de Brito Gitirana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Lennon","family":"de Paiva Coimbra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Pires","family":"de Carvalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Rios-Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7832-8717","authenticated-orcid":false,"given":"Leandro","family":"Miranda-Alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"38319_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/S0044-8486(01)00596-8","volume":"202","author":"U Abdu","year":"2001","unstructured":"Abdu U, Barki A, Karplus I et al (2001) Physiological effects of methyl farnesoate and pyriproxyfen on wintering female crayfish Cherax quadricarinatus. 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