{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:18:46Z","timestamp":1791307126030,"version":"4.3.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2009,11,3]],"date-time":"2009-11-03T00:00:00Z","timestamp":1257206400000},"content-version":"vor","delay-in-days":2164,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["setac.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The pharmaceutical industry gives high priority to animal welfare in the process of drug discovery and safety assessment. In the context of environmental assessments of active pharmaceutical ingredients (APIs), existing U.S. Food and Drug Administration and draft European regulations may require testing of APIs for acute ecotoxicity to algae, daphnids, and fish (base-set ecotoxicity data used to derive the predicted no-effect concentration [PNECwater] from the most sensitive of three species). Subject to regulatory approval, it is proposed that testing can be moved from fish median lethal concentration (LC50) testing (typically using \u2a7e42 fish\/API) to acute threshold tests using fewer fish (typically 10 fish\/API). To support this strategy, we have collated base-set ecotoxicity data from regulatory studies of 91 APIs (names coded for commercial reasons). For 73 of the 91 APIs, the algal median effect concentration (EC50) and daphnid EC50 values were lower than or equal to the fish LC50 data. Thus, for approximately 80% of these APIs, algal and daphnid acute EC50 data could have been used in the absence offish LC50 data to derive PNECwater values. For the other 18 APIs, use of an acute threshold test with a step-down factor of 3.2 is predicted to give comparable PNECwater outcomes. Based on this preliminary scenario of 91 APIs, this approach is predicted to reduce the total number offish used from 3,822 to 1,025 (\u223c73%). The present study, although preliminary, suggests that the current regulatory requirement for fish LC50 data regarding APIs should be succeeded by fish acute threshold (step-down) test data, thereby achieving significant animal welfare benefits with no loss of data for PNECwater estimates.<\/jats:p>","DOI":"10.1897\/02-558","type":"journal-article","created":{"date-parts":[[2005,3,19]],"date-time":"2005-03-19T08:46:24Z","timestamp":1111221984000},"page":"3031-3036","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["A strategy to reduce the numbers of fish used in acute ecotoxicity testing of pharmaceuticals"],"prefix":"10.1093","volume":"22","author":[{"given":"Thomas H.","family":"Hutchinson","sequence":"first","affiliation":[{"name":"AstraZeneca Global Safety Health and Environment, Brixham Environmental Laboratory, TQ5 8BA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Barrett","sequence":"additional","affiliation":[{"name":"AstraZeneca Global Safety Health and Environment, Brixham Environmental Laboratory, TQ5 8BA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Buzby","sequence":"additional","affiliation":[{"name":"Merck, P.O. Box 200, Two Merck Drive, Whitehouse Station, New Jersey 08889, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Constable","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, 2200 Renaissance Boulevard, King of Prussia, Pennsylvania 19406\u20130939, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, WSJ-106.223, Lichtstrasse 35, CH-4002 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Hayes","sequence":"additional","affiliation":[{"name":"Bristol-Myers-Squibb, P.O. Box 192, New Brunswick, New Jersey 08903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duane","family":"Huggett","sequence":"additional","affiliation":[{"name":"Pfizer Research and Development, Groton Laboratories, Eastern Point Road, Groton, Connecticut 06340, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Laenge","sequence":"additional","affiliation":[{"name":"Schering AG, M\u00fcllerstr. 170\u2013178, D-13342, Berlin 13342, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam D.","family":"Lillicrap","sequence":"additional","affiliation":[{"name":"AstraZeneca Global Safety Health and Environment, Brixham Environmental Laboratory, TQ5 8BA, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg Oliver","family":"Straub","sequence":"additional","affiliation":[{"name":"F. 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