Resolving mechanisms of toxicity while pursuing ecotoxicological relevance? David E. Hinton * , Seth W. Kullman, Ron C. Hardman, David C. Volz, Pei-Jen Chen, Michael Carney, David C. Bencic Laboratory of Molecular Aquatic Toxicology, Division of Environmental Sciences and Policy, Nicholas School of the Environment and Earth Sciences, Duke University Durham, NC 277-8-0328, USA Abstract Inthisageofmodernbiology,aquatictoxicologicalresearchhaspursuedmechanismsofactionoftoxicants.Thishasprovided potentialtoolsforecotoxicologicinvestigations.However,problemsofbiocomplexityandissuesathigherlevelsofbiologicalorga- nization remain a challenge. In the 1980s and 1990s and continuing to a lesser extent today, organisms residing in highly contam- inatedfieldsitesorexposedinthelaboratorytocalibratedconcentrationsofindividualcompoundswerecarefullyanalyzedfortheir responsestoprioritypollutants.Correlationofbiochemicalandstructuralanalysesinculturedcellsandtissues,aswellastheinvivo exposuresledtotheproductionandapplicationofbiomarkersofexposureandeffectandtoourawarenessofgenotoxicityandits chronicmanifestations,suchasneoplasms,inwildfishes.Togainacceptanceofthesefindingsinthegreaterenvironmentaltoxicol- ogycommunity,‘‘validationofthemodel’’versusother,better-establishedoftenrodentmodels,wasnecessaryandbecameamajor focus. Resultant biomarkers were applied to heavily contaminated and reference field sites as part of effects assessment and with investigations following large-scale disasters such as oil spills or industrial accidents. Overthepast15years,inthelaboratory,smallaquariumfishmodelssuchasmedaka(Oryzias latipes),zebrafish(Danio rerio), platyfish (Xiphophorus species), fathead minnow (Pimephales promelas), and sheepshead minnow (Cyprinodon variegatus) were increasingly used establishing mechanisms of toxicants. Today, the same organisms provide reliable information at higher levels ofbiologicalorganizationrelevanttoecotoxicology.Wereviewstudiesresolvingmechanismsoftoxicityanddiscusswaystoaddress biocomplexity, mixtures of contaminants, and the need to relate individual level responses to populations and communities. Ó 2005 Elsevier Ltd. All rights reserved. 1. Introduction Regardless of their source of entry to the environ- ment, the aquatic medium is the repository for a large array of stressor chemicals (Long and Buchman, 1990; Mackay et al., 1992a; Mackay et al., 1992b; Tanabe etal.,2004).Disturbancesinnaturalaquaticbiotaarise following exposure to complex mixtures of contami- nantsinwaterordietoverachronicduration(Hopkins et al., 2004; Klerks, 1999; Long and Buchman, 1990; Moore,2002).Throughtheuseofanexpandingaquatic toxicologytoolkit,effectsofstressorchemicalsonaqua- tic organisms are being determined in an integrative manneronindividuals;and,asisreviewedbelow,inspe- cific instances, extended to population and community levels of biological organization as well. To understand how stressors affect organisms, it is necessary to understand effects at various levels of bio- logicalorganizationrangingfrommoleculartotheindi- vidual (Moore, 2002; Eggen et al., 2004; Segner and Cravedi, 2001). And, we often must understand sub- lethal effects that arise from exposure at all life stages (embryonic, larval, juvenile and adult) (Lawrence, 2003). As we shall demonstrate, small aquarium fish 0025-326X/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.marpolbul.2005.07.020 * Corresponding author. Tel.: +1 919 613 8038; fax: +1 919 684 8741. E-mail address: dhinton@duke.edu (D.E. Hinton). www.elsevier.com/locate/marpolbul Marine Pollution Bulletin 51 (2005) 635–648