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The metabolism of NDMA produces formaldehyde, another alkylating agent and DBP. Both compounds are generated from natural and anthropogenic sources, but the safety restrictions applied to NDMA do not extend to the uses of formaldehyde. Hence, potential health and ecological risks are of concern. Due to limited information on the long\u2010term effects of exposure to these compounds at environmentally relevant concentrations, this work aimed to compare the transgenerational reproductive and developmental toxicity of separate exposures to NDMA or its metabolite formaldehyde in <jats:styled-content style=\"fixed-case\"><jats:italic>Drosophila melanogaster<\/jats:italic><\/jats:styled-content> over four generations. The parental flies were fed NDMA or formaldehyde (1.19E\u221206 to 5\u2009mM) for 48\u2009h during the third larval instar. Subsequent offspring (F1\u2013F3) were grown under compound\u2010free conditions. In the parental generation, both exposures modified the time to emergence and reduced the number of progenies. NDMA, but not formaldehyde, was lethal, affected fertility, and weakly induced malformations. In the next generations, both exposures induced malformed flies and modified the number of offspring. Reproductive toxicity and malformations were maintained for at least three generations, suggesting that detrimental effects could extend to unexposed offspring. This is the first study reporting the associated individual transgenerational effects on reproduction and development between NDMA and its metabolite formaldehyde in <jats:styled-content style=\"fixed-case\"><jats:italic>D. melanogaster<\/jats:italic><\/jats:styled-content>, highlighting the relevance of evaluating multiple generations to accurately determine the health and environmental risks of pollutants.<\/jats:p>","DOI":"10.1002\/jat.4749","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T23:21:26Z","timestamp":1736292086000},"page":"841-857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Transgenerational Reproductive and Developmental Toxicity Induced by <i>N<\/i>\u2010Nitrosodimethylamine and Its Metabolite Formaldehyde in <scp><i>Drosophila melanogaster<\/i><\/scp>"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7195-3674","authenticated-orcid":false,"given":"Oscar\u00a0Eduardo","family":"Tabares\u2010Mosquera","sequence":"first","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Toxicolog\u00eda Ambiental\u2010Banco de Moscas, Facultad de Ciencias Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier\u00a0Andr\u00e9s","family":"Ju\u00e1rez\u2010D\u00edaz","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular, Facultad de Ciencias Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Camacho\u2010Carranza","sequence":"additional","affiliation":[{"name":"Departamento de Medicina Gen\u00f3mica y Toxicolog\u00eda Ambiental, Instituto de Investigaciones Biom\u00e9dicas Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Ramos\u2010Morales","sequence":"additional","affiliation":[{"name":"Laboratorio de Gen\u00e9tica y Toxicolog\u00eda Ambiental\u2010Banco de Moscas, Facultad de Ciencias Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"AAT Bioquest Inc.2024. \u201cQuest Graph\u2122 LC50 Calculator.\u201d AAT Bioquest.https:\/\/www.aatbio.com\/tools\/lc50\u2010calculator."},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2022.110284"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00128\u2010013\u20101083\u20107"},{"key":"e_1_2_8_5_1","unstructured":"ATSDR (Agency for Toxic Substances and Disease Registry).2023. \u201cToxicological Profile forN\u2010Nitrosodimethylamine (NDMA).\u201d Atlanta GA USA April 2023. 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