title: Physiological and molecular effect assessment versus physico-chemistry based mode of action schemes: Daphnia magna exposed to narcotics and polar narcotics.
abstract: Structural analogues are assumed to elicit toxicity via similar predominant modes of action (MOAs). Currently, MOA categorization of chemicals in environmental risk assessment is mainly based on the physicochemical properties of potential toxicants. It is often not known whether such classification schemes are also supported by mechanistic biological data. In this study, the toxic effects of two groups of structural analogues (alcohols and anilines) with predefined MOA (narcotics and polar narcotics) were investigated at different levels of biological organization (gene transcription, energy reserves, and growth). Chemical similarity was not indicative of a comparable degree of toxicity and a similar biological response. Categorization of the test chemicals based on the different biological responses (growth, energy use, and gene transcription) did not result in a classification of the predefined narcotics versus the predefined polar narcotics. Moreover, gene transcription based clustering profiles were indicative of the observed effects at higher level of biological organization. Furthermore, a small set of classifier genes could be identified that was discriminative for the clustering pattern. These classifier genes covaried with the organismal and physiological responses. Compared to the physico-chemistry based MOA classification, integrated biological multilevel effect assessment can provide the necessary MOA information that is crucial in high-quality environmental risk assessment. Our findings support the view that transcriptomics tools hold considerable promise to be used in biological response based mechanistic profiling of potential (eco)toxicants.
authors.affiliation: Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium. nathalie.dom@ua.ac.be
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dom
authors.forename: Lucia
authors.initials: L
authors.lastname: Vergauwen
authors.forename: Tine
authors.initials: T
authors.lastname: Vandenbrouck
authors.forename: Mieke
authors.initials: M
authors.lastname: Jansen
authors.forename: Ronny
authors.initials: R
authors.lastname: Blust
authors.forename: Dries
authors.initials: D
authors.lastname: Knapen
mesh_terms: D000818:Animals; D055598:Chemical Phenomena / Q000187:drug effects*; D016000:Cluster Analysis; D003621:Daphnia / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects; D004781:Environmental Exposure / Q000032:analysis*; D020869:Gene Expression Profiling; D016018:Least-Squares Analysis; D009294:Narcotics / Q000737:chemistry* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D009294:Narcotics; D012333:RNA, Messenger