title: Which Molecular Features Affect the Intrinsic Hepatic Clearance Rate of Ionizable Organic Chemicals in Fish?
abstract: Greater knowledge of biotransformation rates for ionizable organic compounds (IOCs) in fish is required to properly assess the bioaccumulation potential of many environmentally relevant contaminants. In this study, we measured in vitro hepatic clearance rates for 50 IOCs using a pooled batch of liver S9 fractions isolated from rainbow trout (Oncorhynchus mykiss). The IOCs included four types of strongly ionized acids (carboxylates, phenolates, sulfonates, and sulfates), three types of strongly ionized bases (primary, secondary, tertiary amines), and a pair of quaternary ammonium compounds (QACs). Included in this test set were several surfactants and a series of beta-blockers. For linear alkyl chain IOC analogues, biotransformation enzymes appeared to act directly on the charged terminal group, with the highest clearance rates for tertiary amines and sulfates and no clearance of QACs. Clearance rates for C12-IOCs were higher than those for C8-IOC analogues. Several analogue series with multiple alkyl chains, branched alkyl chains, aromatic rings, and nonaromatic rings were evaluated. The likelihood of multiple reaction pathways made it difficult to relate all differences in clearance to specific molecular features the tested IOCs. Future analysis of primary metabolites in the S9 assay is recommended to further elucidate biotransformation pathways for IOCs in fish.
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University , Utrecht, 3508 TD, The Netherlands.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University , Utrecht, 3508 TD, The Netherlands.
authors.forename: Joop L M
authors.initials: JL
authors.lastname: Hermens
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University , Utrecht, 3508 TD, The Netherlands.
authors.forename: Michiel T O
authors.initials: MT
authors.lastname: Jonker
authors.affiliation: Department of Physical and Environmental Sciences, University of Toronto Scarborough , Toronto, Ontario M1C 1A4, Canada.|ARC Arnot Research and Consulting , Toronto, Ontario M4M 1W4, Canada.
authors.forename: Jon A
authors.initials: JA
authors.lastname: Arnot
authors.affiliation: Department of Physical and Environmental Sciences, University of Toronto Scarborough , Toronto, Ontario M1C 1A4, Canada.|ARC Arnot Research and Consulting , Toronto, Ontario M4M 1W4, Canada.
authors.forename: James M
authors.initials: JM
authors.lastname: Armitage
authors.affiliation: ARC Arnot Research and Consulting , Toronto, Ontario M4M 1W4, Canada.
authors.forename: Trevor
authors.initials: T
authors.lastname: Brown
authors.affiliation: US Environmental Protection Agency , Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, Duluth, Minnesota 55804, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Nichols
authors.affiliation: US Environmental Protection Agency , Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, Duluth, Minnesota 55804, United States.
authors.forename: Kellie A
authors.initials: KA
authors.lastname: Fay
authors.affiliation: Institute for Risk Assessment Sciences, Utrecht University , Utrecht, 3508 TD, The Netherlands.
authors.forename: Steven T J
authors.initials: ST
authors.lastname: Droge
mesh_terms: D000818:Animals; D001711:Biotransformation; D008099:Liver / Q000378:metabolism*; D008110:Liver Extracts / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D009930:Organic Chemicals / Q000737:chemistry
chemical_list: D008110:Liver Extracts; D009930:Organic Chemicals