title: Comparison of Measured and Predicted Bioconcentration Estimates of Pharmaceuticals in Fish Plasma and Prediction of Chronic Risk.
abstract: Evaluation of the environmental risk of human pharmaceuticals is now a mandatory component in all new drug applications submitted for approval in EU. With >3000 drugs currently in use, it is not feasible to test each active ingredient, so prioritization is key. A recent review has listed nine prioritization approaches including the fish plasma model (FPM). The present paper focuses on comparison of measured and predicted fish plasma bioconcentration factors (BCFs) of four common over-the-counter/prescribed pharmaceuticals: norethindrone (NET), ibuprofen (IBU), verapamil (VER) and clozapine (CLZ). The measured data were obtained from the earlier published fish BCF studies. The measured BCF estimates of NET, IBU, VER and CLZ were 13.4, 1.4, 0.7 and 31.2, while the corresponding predicted BCFs (based log Kow at pH 7) were 19, 1.0, 7.6 and 30, respectively. These results indicate that the predicted BCFs matched well the measured values. The BCF estimates were used to calculate the human: fish plasma concentration ratios of each drug to predict potential risk to fish. The plasma ratio results show the following order of risk potential for fish: NET > CLZ > VER > IBU. The FPM has value in prioritizing pharmaceutical products for ecotoxicological assessments.
authors.affiliation: 701 Princeton South Corporate Center, Ewing, NJ, 08628, USA. Gopinath.Nallani@fmc.com.
authors.forename: Gopinath
authors.initials: G
authors.lastname: Nallani
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton, TX, 76203, USA.
authors.forename: Barney
authors.initials: B
authors.lastname: Venables
authors.affiliation: Pfizer Global Research and Development, Eastern Point Rd, Groton, CT, 06340, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Constantine
authors.affiliation: Environmental Risk Assessment, Waterborne Environmental Inc., Lessburg, VA, USA.
authors.forename: Duane
authors.initials: D
authors.lastname: Huggett
mesh_terms: D000818:Animals; D003024:Clozapine / Q000097:blood; D004784:Environmental Monitoring / Q000379:methods*; D005399:Fishes / Q000097:blood*; D007052:Ibuprofen / Q000097:blood; D008962:Models, Theoretical; D009640:Norethindrone / Q000097:blood; D018570:Risk Assessment; D014700:Verapamil / Q000097:blood; D014874:Water Pollutants, Chemical / Q000097:blood*
chemical_list: D014874:Water Pollutants, Chemical; D014700:Verapamil; D003024:Clozapine; D009640:Norethindrone; D007052:Ibuprofen
keywords: BCF; Effect ratio; Environmental risk assessment; Fish plasma model; Pharmaceuticals