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Disposal of unwanted, leftover medications by flushing into sewers has been considered a secondary route\u2014one that does not contribute substantially to overall environmental loadings. The present study presents the first comprehensive examination of secondary routes of API release to the environment and for direct but unintentional human exposure. These include bathing, washing, and laundering, all of which release APIs remaining on the skin from the use of high-content dermal applications or from excretion to the skin via sweating, and disposal of unused and partially used high-content devices. Also discussed are the health hazards associated with: partially used devices, medication disposal practices of consumers, and interpersonal dermal transfer of API residues. Understanding these secondary routes is important from the perspective of pollution prevention, because actions can be designed more easily for reducing the environmental impact of APIs compared with the route of direct excretion (via urine and feces), for reducing the incidence of unintentional and purposeful poisonings of humans and pets, and for improving the quality and cost-effectiveness of health care. Overall, unintentional exposure to APIs for humans via these routes is possibly more important than exposure to trace residues recycled from the environment in drinking water or foods.<\/jats:p>","DOI":"10.1897\/08-382.1","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T15:45:45Z","timestamp":1240328745000},"page":"2495-2521","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":205,"title":["Environmental footprint of pharmaceuticals: The significance of factors beyond direct excretion to sewers"],"prefix":"10.1093","volume":"28","author":[{"given":"Christian G.","family":"Daughton","sequence":"first","affiliation":[{"name":"Environmental Sciences Division, National Exposure Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 944 East Harmon Avenue, Las Vegas, Nevada 89119"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilene S.","family":"Ruhoy","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine, Touro University Nevada, Henderson, Nevada 89014, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,1]]},"reference":[{"key":"2025010317062792400_bib1","volume-title":"Pharmaceuticals and personal care products (PPCPs): Relevant literature","author":"Office of Research and Development, U.S. Environmental Protection Agency","year":"2008"},{"key":"2025010317062792400_bib2","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1021\/es011055j","article-title":"Pharmaceuticals, hormones, and other organic wastewater contaminants in U.S. streams, 1999\u20132000: A national reconnaissance","volume":"36","author":"Kolpin","year":"2002","journal-title":"Environ Sci Technol"},{"key":"2025010317062792400_bib3","first-page":"1","volume-title":"Analysis, Fate and Removal of Pharmaceuticals in the Water Cycle, Vol 50","author":"Daughton","year":"2007"},{"key":"2025010317062792400_bib4","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.scitotenv.2008.03.027","article-title":"A comparison of human pharmaceutical concentrations in raw municipal wastewater and yellowwater","volume":"399","author":"Winker","year":"2008","journal-title":"Sci Total Environ"},{"key":"2025010317062792400_bib5","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1038\/sj.embor.7400307","article-title":"The environmental side effects of medication: How are human and veterinary medicines in soils and water bodies affecting human and environmental health?","volume":"5","author":"Boxall","year":"2002","journal-title":"EMBO Rep"},{"key":"2025010317062792400_bib6","first-page":"1","article-title":"Veterinary medicines in the environment","volume":"180","author":"Boxall","year":"2004","journal-title":"Rev Environ Contam Toxicol"},{"key":"2025010317062792400_bib7","doi-asserted-by":"crossref","first-page":"3456","DOI":"10.1021\/es063017b","article-title":"Effects of human pharmaceuticals on aquatic life: Next steps","volume":"40","author":"Cunningham","year":"2006","journal-title":"Environ Sci Technol"},{"key":"2025010317062792400_bib8","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/j.envint.2008.05.002","article-title":"Beyond the medicine cabinet: An analysis of where and why medications accumulate","volume":"34","author":"Ruhoy","year":"2008","journal-title":"Environ Int"},{"key":"2025010317062792400_bib9","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1289\/ehp.5947","article-title":"Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health. 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