title: Multi-criteria decision analysis of test endpoints for detecting the effects of endocrine active substances in fish full life cycle tests.
abstract: Fish full life cycle (FFLC) tests are increasingly required in the ecotoxicological assessment of endocrine active substances. However, FFLC tests have not been internationally standardized or validated, and it is currently unclear how such tests should best be designed to provide statistically sound and ecologically relevant results. This study describes how the technique of multi-criteria decision analysis (MCDA) was used to elicit the views of fish ecologists, aquatic ecotoxicologists and statisticians on optimal experimental designs for assessing the effects of endocrine active chemicals on fish. In MCDA qualitative criteria (that can be valued, but not quantified) and quantitative criteria can be used in a structured decision-making process. The aim of the present application of MCDA is to present a logical means of collating both data and expert opinions on the best way to focus FFLC tests on endocrine active substances. The analyses are presented to demonstrate how MCDA can be used in this context. Each of 3 workgroups focused on 1 of 3 species: fathead minnow (Pimephales promelas), Japanese medaka (Oryzias latipes), and zebrafish (Danio rerio). Test endpoints (e.g., fecundity, growth, gonadal histopathology) were scored for each species for various desirable features such as statistical power and ecological relevance, with the importance of these features determined by assigning weights to them, using a swing weighting procedure. The endpoint F1 fertilization success consistently emerged as a preferred option for all species. In addition, some endpoints scored highly in particular species, such as development of secondary sexual characteristics (fathead minnow) and sex ratio (zebrafish). Other endpoints such as hatching success ranked relatively highly and should be considered as useful endpoints to measure in tests with any of the fish species. MCDA also indicated relatively less preferred endpoints in fish life cycle tests. For example, intensive histopathology consistently ranked low, as did measurement of diagnostic biomarkers, such as vitellogenin, most likely due to the high costs of these methods or their limited ecological relevance. Life cycle tests typically do not focus on identifying toxic modes and/or mechanisms of action, but rather, single chemical concentration-response relationships for endpoints (e.g., survival, growth, reproduction) that can be translated into evaluation of risk. It is, therefore, likely to be an inefficient use of limited resources to measure these mechanism-specific endpoints in life cycle tests, unless the value of such endpoints for answering particular questions justifies their integration in specific case studies.
authors.affiliation: WCA Environment Limited, Brunel House, Volunteer Way, Faringdon, Oxfordshire, SN7 7YR, United Kingdom. mark.crane@wca-environment.com
authors.forename: Mark
authors.initials: M
authors.lastname: Crane
authors.forename: Melanie
authors.initials: M
authors.lastname: Gross
authors.forename: Peter
authors.initials: P
authors.lastname: Matthiessen
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
authors.forename: Stephen
authors.initials: S
authors.lastname: Axford
authors.forename: Poul
authors.initials: P
authors.lastname: Bjerregaard
authors.forename: Ross
authors.initials: R
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Chapman
authors.forename: Michael
authors.initials: M
authors.lastname: Dorgeloh
authors.forename: Malyka
authors.initials: M
authors.lastname: Galay-Burgos
authors.forename: John
authors.initials: J
authors.lastname: Green
authors.forename: Charles
authors.initials: C
authors.lastname: Hazlerigg
authors.forename: John
authors.initials: J
authors.lastname: Janssen
authors.forename: Kai
authors.initials: K
authors.lastname: Lorenzen
authors.forename: Joanne
authors.initials: J
authors.lastname: Parrott
authors.forename: Hans
authors.initials: H
authors.lastname: Rufli
authors.forename: Christoph
authors.initials: C
authors.lastname: Schäfers
authors.forename: Masanori
authors.initials: M
authors.lastname: Seki
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Stolzenberg
authors.forename: Nelly
authors.initials: N
authors.lastname: van der Hoeven
authors.forename: Dick
authors.initials: D
authors.lastname: Vethaak
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Winfield
authors.forename: Sabine
authors.initials: S
authors.lastname: Zok
authors.forename: James
authors.initials: J
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D003661:Decision Support Techniques; D054750:Ecotoxicology / Q000379:methods*; D052244:Endocrine Disruptors / Q000633:toxicity*; D023381:Endpoint Determination / Q000379:methods*; D005260:Female; D005399:Fishes / Q000254:growth & development*; D008018:Life Cycle Stages / Q000187:drug effects*; D008297:Male; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D052244:Endocrine Disruptors