{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:23:36Z","timestamp":1772785416772,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2005,12,1]],"date-time":"2005-12-01T00:00:00Z","timestamp":1133395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2009,12,9]],"date-time":"2009-12-09T00:00:00Z","timestamp":1260316800000},"content-version":"vor","delay-in-days":1469,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["setac.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The joint toxic effects of known binary and multiple organic chemical mixtures to the fathead minnow (Pimephales promelas) were defined at both the 96-h 50% lethal effect concentration (LC50) and sublethal (32-d growth) response levels for toxicants with a narcosis I, narcosis II, or uncoupler of oxidative phosphoralation mode of toxic action. Experiments were designed to define the degree of additive joint toxicity for mixtures of specific xenobiotics that are believed to act through a similar or different primary mode of toxic action. Our results support the general conclusion that concentration addition is expected for the joint toxicity of similarly acting toxicants. When chemicals were thought to act by a dissimilar mechanism, the combined effects we observed at both of the response levels tested were less than predicted by concentration addition, but usually more toxic than that predicted by the independent action\/response addition model. It was demonstrated in multichemical mixtures that several toxicants can act together in a nearly additive fashion to produce effects even when they are present at concentrations below their individual no-observed-effect concentration. Concentration-response relationships for test chemicals at both the lethal and sublethal responses were defined for each of the three modes of toxic action studied. When normalized for potency, it was observed that one relationship could be defined to predict lethality to juvenile fathead minnows when exposed to individual chemicals with either a narcosis I, narcosis II, or uncoupler mode of toxic action. These sublethal relationships were similar for the narcosis I and narcosis II test chemicals, but a steeper response was observed for tests conducted with uncouplers.<\/jats:p>","DOI":"10.1897\/05-094r.1","type":"journal-article","created":{"date-parts":[[2005,11,23]],"date-time":"2005-11-23T22:15:56Z","timestamp":1132784156000},"page":"3117-3127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["A comparison of the lethal and sublethal toxicity of organic chemical mixtures to the fathead minnow (<i>Pimephales promelas<\/i>)"],"prefix":"10.1093","volume":"24","author":[{"given":"Steven J.","family":"Broderius","sequence":"first","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota 55804\u20132595"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael D.","family":"Kahl","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota 55804\u20132595"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory E.","family":"Elonen","sequence":"additional","affiliation":[{"name":"Computer Science Corporation, Suite 400, 1 East First Street, Duluth, Minnesota 55802 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean E.","family":"Hammermeister","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, 6201 Congdon Boulevard, Duluth, Minnesota 55804\u20132595"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilynn D.","family":"Hoglund","sequence":"additional","affiliation":[{"name":"U.S. Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Gulf Ecology Division, 1 Sabine Island Drive, Gulf Breeze, Florida 32561"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2005,12,1]]},"reference":[{"key":"2025010318053965800_bib1","author":"European Inland Fisheries Advisory Commission Working Party on Water Quality Criteria for European Freshwater Fish.","year":"1980"},{"key":"2025010318053965800_bib2","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0166-445X(88)90017-3","article-title":"The joint acute toxicity to Daphnia magna of industrial organic chemicals at low concentrations","volume":"12","author":"Deneer","year":"1988","journal-title":"Aquat Toxicol"},{"key":"2025010318053965800_bib3","author":"European Centre for Ecotoxicology and Toxicology of Chemicals.","year":"2001"},{"key":"2025010318053965800_bib4","first-page":"273","article-title":"Quantitative structure-activity relationships in aquatic toxicity studies of chemicals and complex mixtures of chemicals","volume":"4","author":"Hermens","year":"1985","journal-title":"Environ Toxicol Chem"},{"key":"2025010318053965800_bib5","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/0147-6513(84)90007-1","article-title":"Quantitative structure-activity relationships and mixture toxicity studies of chloro- and alkylanilines at an acute lethal toxicity level to the guppy (Poecilia reticulata)","volume":"8","author":"Hermens","year":"1984","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010318053965800_bib6","first-page":"941","author":"Faust","year":"1993"},{"key":"2025010318053965800_bib7","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1897\/1551-5028(2000)019<2341:POTTOM>2.3.CO;2","article-title":"Predictability of the toxicity of multiple chemical mixtures to Vibrio fischeri: Mixtures composed of similarly acting chemicals","volume":"19","author":"Altenburger","year":"2000","journal-title":"Environ Toxicol Chem"},{"key":"2025010318053965800_bib8","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1002\/etc.5620190927","article-title":"Predictability of the toxicity of a multiple mixture of dissimilarly acting chemicals to Vibrio fischeri. Environ","volume":"19","author":"Backhaus","year":"2000","journal-title":"Toxicol Chem"},{"key":"2025010318053965800_bib9","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0166-445X(01)00187-4","article-title":"Predicting the joint algal toxicity of multicomponent s-triazine mixtures at low-effect concentrations of individual toxicants","volume":"56","author":"Faust","year":"2001","journal-title":"Aquat Toxicol"},{"key":"2025010318053965800_bib10","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1016\/j.chemosphere.2003.09.031","article-title":"Mechanism of concentration-addition toxicity: They are different for nonpolar narcotic chemicals, polar narcotic chemicals, and reactive chemicals","volume":"54","author":"Lin","year":"2004","journal-title":"Chemosphere"},{"key":"2025010318053965800_bib11","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/0147-6513(80)90043-3","article-title":"Structure-activity relationships and additivity in fish toxicities of environmental pollutants","volume":"4","author":"Konemann","year":"1980","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010318053965800_bib12","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0300-483X(81)90132-3","article-title":"Fish toxicity tests with mixtures of more than two chemicals: A proposal for a quantitative approach and experimental results","volume":"19","author":"Konemann","year":"1981","journal-title":"Toxicology"},{"key":"2025010318053965800_bib13","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/0147-6513(82)90020-3","article-title":"Joint toxicity of 8 and 24 chemicals to the guppy (Poecillia reticulata)","volume":"6","author":"Hermens","year":"1982","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010318053965800_bib14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/0166-445X(84)90012-2","article-title":"Joint effects of a mixture of 14 chemicals on mortality and inhibition of reproduction of Daphnia magna","volume":"5","author":"Hermens","year":"1984","journal-title":"Aquat Toxicol"},{"key":"2025010318053965800_bib15","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0147-6513(85)90049-1","article-title":"Joint toxicity of mixtures of groups of organic aquatic pollutants to the guppy (Poecilia reticulata)","volume":"9","author":"Hermens","year":"1985","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010318053965800_bib16","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/0147-6513(88)90044-9","article-title":"Growth of Daphnia magna exposed to mixtures of chemicals with diverse modes of action","volume":"15","author":"Deneer","year":"1988","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010318053965800_bib17","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/etc.5620140920","article-title":"Use of joint toxic response to define the primary mode of toxic action for diverse industrial organic chemicals","volume":"14","author":"Broderius","year":"1995","journal-title":"Environ Toxicol Chem"},{"key":"2025010318053965800_bib18","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0278-6915(97)00088-4","article-title":"Regulations for combined effects of pollutants: Consequences from risk assessment in aquatic toxicology","volume":"34","author":"Altenberger","year":"1996","journal-title":"Food Chem Toxicol"},{"key":"2025010318053965800_bib19","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1002\/(SICI)1526-4998(200006)56:6<516::AID-PS163>3.0.CO;2-0","article-title":"Toxicity of mixtures of pesticides in aquatic systems","volume":"56","author":"Deneer","year":"2000","journal-title":"Pest Manag Sci"},{"key":"2025010318053965800_bib20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0166-445X(02)00133-9","article-title":"Joint algal toxicity of 16 dissimilarly acting chemicals is predictable by the concept of independent action","volume":"63","author":"Faust","year":"2003","journal-title":"Aquat Toxicol"},{"key":"2025010318053965800_bib21","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-94-015-8520-0_6","volume-title":"Risk Assessment of Chemicals: An Introduction","author":"van Leeuwen","year":"1995"},{"key":"2025010318053965800_bib22","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1139\/f83-096","article-title":"Structure-toxicity relationships for the fathead minnow, Pimephales promelas: Narcotic industrial chemicals","volume":"40","author":"Veith","year":"1983","journal-title":"Can J Fish Aquat Sci"},{"key":"2025010318053965800_bib23","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1289\/ehp.9087207","article-title":"Rules for distinguishing toxicants that cause Type I and Type II narcosis syndromes","volume":"87","author":"Veith","year":"1990","journal-title":"Environ Health Perspect"},{"key":"2025010318053965800_bib24","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1289\/ehp.9087213","article-title":"Uncouplers of oxidative phosphorylation","volume":"87","author":"Terada","year":"1990","journal-title":"Environ Health Perspect"},{"key":"2025010318053965800_bib25","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1289\/ehp.9087219","article-title":"Electrophiles and acute toxicity to fish","volume":"87","author":"Hermens","year":"1990","journal-title":"Environ Health Perspect"},{"key":"2025010318053965800_bib26","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3109\/00498258709044200","article-title":"A QSAR study of the acute toxicity of some industrial organic chemicals to goldfish. Narcosis, electrophile, and proelectrophile mechanisms","volume":"7","author":"Lipnick","year":"1987","journal-title":"Xenobiotica"},{"key":"2025010318053965800_bib27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0166-445X(85)90026-8","article-title":"Acute toxicity of organic chemical mixtures to the fathead minnow","volume":"6","author":"Broderius","year":"1985","journal-title":"Aquat Toxicol"},{"key":"2025010318053965800_bib28","first-page":"133","volume-title":"Annual Book of ASTM Standards","author":"American Society for Testing and Materials.","year":"2004"},{"key":"2025010318053965800_bib29","first-page":"460","volume-title":"Annual Book of ASTM Standards","author":"American Society for Testing and Materials.","year":"2004"},{"key":"2025010318053965800_bib30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0043-1354(70)90018-7","article-title":"Measurement of pollutant toxicity to fish. II. Utilizing and applying bioassay results","volume":"4","author":"Sprague","year":"1970","journal-title":"Water Res"},{"key":"2025010318053965800_bib31","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/BF02322290","article-title":"Diequantitativen probleme der pharmakologie","volume":"27","author":"Loewe","year":"1928","journal-title":"Ergeb Physiol Biol Chem Exp Pharmakol"},{"key":"2025010318053965800_bib32","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1021\/es60130a004","article-title":"Trimmed Spearman-Karber method for estimating median lethal concentrations in toxicity bioassays","volume":"11","author":"Hamilton","year":"1977","journal-title":"Environ Sci Technol"},{"key":"2025010318053965800_bib33","first-page":"107","volume-title":"Aquatic Toxicology and Risk Assessment","author":"Broderius","year":"1991"},{"key":"2025010318053965800_bib34","volume-title":"Toxicity Relationship Analysis Program","author":"U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory","year":"2002"},{"key":"2025010318053965800_bib35","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0045-6535(92)90285-Y","article-title":"A proposal to define quality objectives for aquatic life for mixtures of chemical substances","volume":"25","author":"Calamari","year":"1992","journal-title":"Chemosphere"},{"key":"2025010318053965800_bib36","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0147-6513(02)00047-7","article-title":"Water quality objectives for mixtures of toxic chemicals: Problems and perspectives","volume":"54","author":"Vighi","year":"2003","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025010318053965800_bib37","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1002\/etc.5620190803","article-title":"Technical basis for narcotic chemicals and polycyclic aromatic hydrocarbon criteria. I. Water and tissue","volume":"19","author":"Di Toro","year":"2000","journal-title":"Environ Toxicol Chem"},{"key":"2025010318053965800_bib38","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.1021\/es049528k","article-title":"What contributes to the combined effect of a complex mixture?","volume":"38","author":"Altenburger","year":"2004","journal-title":"Environ Sci Technol"},{"key":"2025010318053965800_bib39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00244-004-0056-6","article-title":"Toxicity assessment of pesticide mixtures typical of the Sacramento-San Joaquin Delta using Chironomus tentans","volume":"48","author":"Lydy","year":"2004","journal-title":"Arch Environ Contam Toxicol"},{"key":"2025010318053965800_bib40","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2307\/2528279","article-title":"A comparison of two approaches to the construction of models for quantal responses to mixtures of drugs","volume":"23","author":"Plackett","year":"1967","journal-title":"Biometrics"},{"key":"2025010318053965800_bib41","volume-title":"Acute Toxicities of Organic Chemicals to Fathead Minnows (Pime-phales promelas)","author":"Geiger","year":"1985"},{"key":"2025010318053965800_bib42","volume-title":"Ecotoxicology Database (ECOTOX)","author":"U.S. Environmental Protection Agency.","year":"2004"},{"key":"2025010318053965800_bib43","volume-title":"Acute Toxicities of Organic Chemicals to Fathead Minnows (Pime-phales promelas)","author":"Brooke","year":"1984"},{"key":"2025010318053965800_bib44","volume-title":"Subchronic Toxicities of Industrial and Agricultural Chemicals to Fathead Minnows (Pimephales promelas)","author":"Call","year":"1992"},{"key":"2025010318053965800_bib45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/BF01056076","article-title":"Effects of naphthalene and benzene on fathead minnows and rainbow trout","volume":"11","author":"DeGraeve","year":"1982","journal-title":"Arch Environ Contam Toxicol"},{"key":"2025010318053965800_bib46","volume-title":"Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales promelas)","author":"Geiger","year":"1986"},{"key":"2025010318053965800_bib47","volume-title":"Acute Toxicities of Organic Chemicals to Fathead Minnows (Pimephales promelas)","author":"Geiger","year":"1988"}],"container-title":["Environmental Toxicology and Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1897%2F05-094R.1","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/24\/12\/3117\/59674559\/5620241217.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/etc\/article-pdf\/24\/12\/3117\/59674559\/5620241217.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T18:15:36Z","timestamp":1735928136000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/etc\/article\/24\/12\/3117\/7770425"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,12,1]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2005,12,1]]},"published-print":{"date-parts":[[2005,12,1]]}},"URL":"https:\/\/doi.org\/10.1897\/05-094r.1","relation":{},"ISSN":["0730-7268","1552-8618"],"issn-type":[{"value":"0730-7268","type":"print"},{"value":"1552-8618","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2005,12,1]]},"published":{"date-parts":[[2005,12,1]]},"assertion":[{"value":"2005-02-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-06-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-12-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}