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This study employed zebrafish (Danio rerio) to evaluate the environmental toxicity of TpPa and elucidate molecular mechanisms. Zebrafish embryos were exposed to 0\u201350 mg\/L TpPa for 120 h, and developmental toxicity, oxidative stress, and physiological and molecular responses were investigated. Results demonstrated that TpPa exposure exerted concentration- and time-dependent effects. Mortality and malformation rates increased significantly from 5 mg\/L, accompanied by reduced body length. The hatching rate showed a biphasic pattern, increasing with concentration at 48 h and decreasing with concentration at 120 h. Spontaneous movement was elevated at 50 mg\/L, while heart rate increased dose-dependently starting from 5 mg\/L at 48 h and from 1 mg\/L at 72 h. Mechanistically, TpPa induced oxidative stress via reactive oxygen species accumulation and impaired the activities of both superoxide dismutase and catalase. These effects activated the p53-mediated apoptotic pathway, reduced the Bcl2\/Bax ratio, and disrupted the GH\/IGF growth axis and neuromotor regulatory pathways, ultimately causing developmental abnormalities. These findings provide critical data for the environmental safety assessment of TpPa, with direct relevance to establishing health monitoring protocols for COF-exposed aquaculture species.<\/jats:p>","DOI":"10.3390\/ani16152282","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T09:11:26Z","timestamp":1784797886000},"page":"2282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toxicity of the Covalent Organic Framework Material TpPa to Zebrafish"],"prefix":"10.3390","volume":"16","author":[{"given":"Cuiming","family":"Huang","sequence":"first","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingui","family":"Lin","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiudan","family":"Yang","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"College of Materials Science and Engineering, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3396-6103","authenticated-orcid":false,"given":"Lijie","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Ecology and Environment, Nanjing Forestry University, Nanjing 210037, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9339-4680","authenticated-orcid":false,"given":"Muting","family":"Yan","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, South China Agricultural University, Guangzhou 510642, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Gong","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Guangdong Province and Hong Kong Region on Marine Bioresource Conservation and Exploitation, South China Agricultural University, Guangzhou 510642, China"},{"name":"Department of Chemistry, Stockholm University, 10691 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155433","DOI":"10.1016\/j.apsusc.2022.155433","article-title":"Designing a novel metal-organic framework@covalent organic framework composite for the selective removal of fluoroquinolones: Adsorption behaviors and theoretical investigation","volume":"609","author":"Lin","year":"2022","journal-title":"Appl. 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