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  • Title: Evaluation of the EMA log kow trigger for fish BCF testing based on data for several human pharmaceuticals.
    Author: Constantine LA, Burden N, Davidson T, Dolan DG, Janer G, Häner A, Lee MR, Maynard SK, Nfon E, Nimrod Perkins A, Ryan JJ, Tell J.
    Journal: Regul Toxicol Pharmacol; 2024 Aug; 151():105651. PubMed ID: 38825065.
    Abstract:
    In the European Medicines Agency (EMA) "Guideline for Environmental Risk Assessment of Medicinal Products for Human Use," a fish bioconcentration factor (BCF) study is triggered in Phase I for pharmaceuticals having log Kow >4.5, to support Persistence, Bioaccumulation and Toxicity (PBT) screening, and in Phase II to assess secondary poisoning and bioaccumulation ('B') potential when log Kow ≥3. The standard sampling schedule outlined in OECD Test Guideline 305 (TG305) may require assessment of approximately 200 fish following exposure to low- and high-test concentrations and a negative control. We report experimental log Kow and BCF values for 64 human pharmaceuticals that were used to evaluate the current BCF testing trigger of log Kow ≥3, and whether a single BCF exposure concentration allows accurate classification of bioaccumulation potential. Our data support raising the BCF testing trigger to log Kow ≥4, and use of a single test concentration. The resulting reduction in the use of fish is consistent with the 3 R s principle and did not adversely affect classification accuracy. An assessment of potential risk of secondary poisoning was also conducted for three drugs classified as either B or vB, and no risks were identified.
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