title: Development of a list of reference chemicals for evaluating alternative methods to in vivo fish bioaccumulation tests.
abstract: The aim to reduce the number of animals in experiments has highlighted the need to develop and validate nonanimal methods as alternatives to bioaccumulation studies using fish. The present study details a novel 3-tier approach to develop a list of reference compounds to aid this process. The approach was based on 1) the inclusion of relevant chemical classes supported by high-quality in vivo data for the bioconcentration factor (BCF), whole-body biotransformation rates (K(met)), and metabolism characterization for rainbow trout (Oncorhynchus mykiss) and common carp (Cyprinus carpio) (tiers I and II); and 2) the refinement to ensure a broad coverage of hydrophobicity, bioconcentration potential, molecular weight, maximum molecular diameter, whole-body biotransformation half-lives, and metabolic pathways (tier III). In silico techniques were employed to predict maximal log BCF and molecular and metabolic properties. Of the 157 compounds considered as reference compounds, 144 were supported by high-quality BCF data, 8 were supported by K(met) data, and 5 were supported by in vivo metabolism data. Additional criteria for refinement of the list of reference compounds were suggested to aid practical implementation in experimental efforts. The present list of reference compounds is anticipated to facilitate the development of alternative approaches, enhance understanding of in vivo and in vitro bioaccumulation relationships, and refine in silico BCF and metabolism predictions.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, United Kingdom.
authors.forename: Neus
authors.initials: N
authors.lastname: Rodriguez-Sanchez
authors.forename: Mark Timothy David
authors.initials: MT
authors.lastname: Cronin
authors.forename: Adam
authors.initials: A
authors.lastname: Lillicrap
authors.forename: Judith Clare
authors.initials: JC
authors.lastname: Madden
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Piechota
authors.forename: Knut Erik
authors.initials: KE
authors.lastname: Tollefsen
mesh_terms: D000818:Animals; D001711:Biotransformation; D002347:Carps / Q000378:metabolism*; D006207:Half-Life; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008962:Models, Theoretical; D008970:Molecular Weight; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D009930:Organic Chemicals / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009930:Organic Chemicals
keywords: Alternative testing; Bioaccumulation; Bioconcentration; In vitro; Reference list