A Generalized Physiologically Based Kinetic Model for Fish for Environmental Risk Assessment of Pharmaceuticals

Jiaqi Wang*, Tom M. Nolte, Stewart F. Owen, Rémy Beaudouin, A. Jan Hendriks, Ad M.J. Ragas

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


An increasing number of pharmaceuticals found in the environment potentially impose adverse effects on organisms such as fish. Physiologically based kinetic (PBK) models are essential risk assessment tools, allowing a mechanistic approach to understanding chemical effects within organisms. However, fish PBK models have been restricted to a few species, limiting the overall applicability given the countless species. Moreover, many pharmaceuticals are ionizable, and fish PBK models accounting for ionization are rare. Here, we developed a generalized PBK model, estimating required parameters as functions of fish and chemical properties. We assessed the model performance for five pharmaceuticals (covering neutral and ionic structures). With biotransformation half-lives (HLs) from EPI Suite, 73 and 41% of the time-course estimations were within a 10-fold and a 3-fold difference from measurements, respectively. The performance improved using experimental biotransformation HLs (87 and 59%, respectively). Estimations for ionizable substances were more accurate than any of the existing species-specific PBK models. The present study is the first to develop a generalized fish PBK model focusing on mechanism-based parameterization and explicitly accounting for ionization. Our generalized model facilitates its application across chemicals and species, improving efficiency for environmental risk assessment and supporting an animal-free toxicity testing paradigm.

Original languageEnglish
Pages (from-to)6500-6510
Number of pages11
JournalEnvironmental Science and Technology
Issue number10
Publication statusPublished - 17 May 2022


  • fish
  • internal concentrations
  • ionization
  • pharmaceuticals
  • physiologically based kinetic model


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