The influence of gill and liver metabolism on the predicted bioconcentration of three pharmaceuticals in fish.
The potential for xenobiotic compounds to bioconcentrate is typically expressed through the bioconcentration factor (BCF), which has gained increased regulatory significance over the past decade. Due to the expense of in vivo bioconcentration studies and the growing regulatory need to assess bioconcentration potential, BCF is often calculated via single-compartment models, using K(OW) as the primary input. Recent efforts to refine BCF models have focused on physiological factors, including the ability of the organism to eliminate the compound through metabolic transformation. This study looks at the ability of in vitro biotransformation assays using S9 fractions to provide an indication of metabolic potential. Given the importance of the fish gill and liver in metabolic transformation, the metabolic loss of ibuprofen, norethindrone and propranolol was measured using rainbow trout (Oncorhynchus mykiss) and channel catfish (Ictalurus punctatus) gill and liver S9 fractions. Metabolic transformation rates (k(M)) were calculated and integrated into a refined BCF model. A significant difference was noted between BCF solely based on K(OW) and BCF including k(M). These studies indicate that the inclusion of k(M) in BCF models can bring predicted bioconcentration estimates closer to in vivo values.
Gomez
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CF
Department of Biological Sciences, University of North Texas, Denton, TX 76208, USA.
Constantine
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L
Huggett
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DB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000633:toxicity; D003280:Contraceptives, Oral, Synthetic / Q000378:metabolism / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D005399:Fishes / Q000378:metabolism*; D005880:Gills / Q000187:drug effects* / Q000378:metabolism; D007052:Ibuprofen / Q000378:metabolism / Q000633:toxicity; D007059:Ictaluridae / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D009640:Norethindrone / Q000378:metabolism / Q000633:toxicity; D017686:Oncorhynchus mykiss / Q000502:physiology; D055553:Prescription Drugs / Q000378:metabolism / Q000633:toxicity*; D011433:Propranolol / Q000378:metabolism / Q000633:toxicity; D014665:Vasodilator Agents / Q000378:metabolism / Q000633:toxicity; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003280:Contraceptives, Oral, Synthetic; D055553:Prescription Drugs; D014665:Vasodilator Agents; D014874:Water Pollutants, Chemical; D011433:Propranolol; D019363:Cytochrome P-450 CYP1A1; D009640:Norethindrone; D007052:Ibuprofen