PARENT SESSION

2P Modelling ecotoxic effects
Poster Hall
8:30 AM - Monday, 28 April 2003

(MOP/156) Proposed reduction in fish acute testing for environmental assessment of human pharmaceuticals.

Hutchinson, T.¹, Barrett, S.¹, Busby, M.², Constable, D.³, Hartmann, A.⁴, Hayes, E.⁵, Huggett, D.⁶, Laenge, R.⁷, Lillicrap, A.¹, Straub, J.⁸, ¹ AstraZeneca Global Safety, Health & Environment, Brixham Environmental Laboratory, UK² Merck & Co., Inc., Whitehouse Station, USA³ GlaxoSmithKline, King of Prussia, USA⁴ Novartis Pharma AG, Basel, Switzerland⁵ Bristol-Myers-Squibb Co., New Brunswick, USA⁶ Pfizer R&D, Groton, USA⁷ Schering AG, Berlin, Germany⁸ F. Hoffman-La Roche Ltd., Basel, Switzerland

ABSTRACT- The pharmaceutical industry gives high priority to animal welfare across drug discovery and safety assessments. In the context of environmental assessments of active pharmaceutical ingredients (APIs), existing US Food & Drug Administration and draft European regulations may require testing of APIs for acute ecotoxicity to algae, daphnids and fish (base set ecotoxicity data). Subject to regulatory approval, it is proposed that there is scope to move from fish full LC50 testing; typically using at least 42 fish per API to simpler acute threshold tests using an estimate 10 fish per API. We have collated base set data from regulatory studies on 91 APIs used to derive the Predicted No-Effect Concentration (PNECwater) based on acute test data from algae, daphnids and fish. For 73 out of 91 APIs, algal EC50 and daphnid EC50 values were lower or equal to the fish LC50 data. Therefore for ca. 80% of these APIs, algal and daphnid acute EC50 data could have been used in the absence of fish LC50 data to derive PNECwater values. For the other 18 APIs, use of a stepwise testing approach (with a step down factor of 3.2 between exposure concentrations) is expected to give comparable PNECwater outcomes. This approach is projected to reduce the total number of fish used by approximately 70%. This study suggests that the current requirement for fish LC50 data on APIs should be succeeded by fish acute threshold (step down) test data, giving benefits for animal welfare with no loss of data for PNECwater calculations.

Key words: fish, animal welfare, environmental assessment, human pharmaceuticals