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However, there is limited information on their toxicity, particularly in in vivo models. In this manuscript, we evaluate the survival, developmental, and reproductive impact of these designer drugs on the model organism Caenorhabditis elegans (C. elegans). For this purpose, adult worms synchronized at the L1 stage were exposed to growing concentrations of 2C-I and 25I-NBOMe. The animal survival rate and the putative effects of the drugs on C. elegans development and reproductive behavior were assessed after 24 h of exposure. A concentration-dependent decrease in animal survival was observed. 25I-NBOMe was approximately six times more toxic than 2C-I (LC50 values\u20141.368 mM for 2C-I and 0.236 mM for 25I-NBOMe). Furthermore, sublethal concentrations of both drugs delayed animal development and reduced the total progeny but not its survival. Overall, these findings underscore the developmental and reproductive risks associated with exposure to 2C-I and 25I-NBOMe, even at sublethal concentrations.<\/jats:p>","DOI":"10.3390\/ijms26073039","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T09:13:26Z","timestamp":1742980406000},"page":"3039","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sublethal Concentrations of 2C-I and 25I-NBOMe Designer Drugs Impact Caenorhabditis elegans Development and Reproductive Behavior"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8142-562X","authenticated-orcid":false,"given":"Eva","family":"Gil-Martins","sequence":"first","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"CIQUP-IMS\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-6011","authenticated-orcid":false,"given":"Daniel Jos\u00e9","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, University Institute of Health Sciences-CESPU, 4585-116 Gandra, Portugal"},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9410-6874","authenticated-orcid":false,"given":"Fernando","family":"Cagide","sequence":"additional","affiliation":[{"name":"CIQUP-IMS\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1050-2402","authenticated-orcid":false,"given":"Fernanda","family":"Borges","sequence":"additional","affiliation":[{"name":"CIQUP-IMS\/Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-7548","authenticated-orcid":false,"given":"Renata","family":"Silva","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Simao, A.Y., Antunes, M., Cabral, E., Oliveira, P., Rosendo, L.M., Brinca, A.T., Alves, E., Marques, H., Rosado, T., and Passarinha, L.A. 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