title: Animal use replacement, reduction, and refinement: development of an integrated testing strategy for bioconcentration of chemicals in fish.
abstract: When addressing the use of fish for the environmental safety of chemicals and effluents, there are many opportunities for applying the principles of the 3Rs: Reduce, Refine, and Replace. The current environmental regulatory testing strategy for bioconcentration and secondary poisoning has been reviewed, and alternative approaches that provide useful information are described. Several approaches can be used to reduce the number of fish used in the Organization for Economic Cooperation and Development (OECD) Test Guideline 305, including alternative in vivo test methods such as the dietary accumulation test and the static exposure approach. The best replacement approach would seem to use read-across, chemical grouping, and quantitative structure-activity relationships with an assessment of the key processes in bioconcentration: Adsorption, distribution, metabolism, and excretion. Biomimetic extraction has particular usefulness in addressing bioavailable chemicals and is in some circumstances capable of predicting uptake. Use of alternative organisms such as invertebrates should also be considered. A single cut-off value for molecular weight and size beyond which no absorption will take place cannot be identified. Recommendations for their use in bioaccumulative (B) categorization schemes are provided. Assessment of biotransformation with in vitro assays and in silico approaches holds significant promise. Further research is needed to identify their variability and confidence limits and the ways to use this as a basis to estimate bioconcentration factors. A tiered bioconcentration testing strategy has been developed taking account of the alternatives discussed.
authors.affiliation: DuPont Coordination Center, Antoon Spinoystraat 6, 2800 Mechelen, Belgium. watze.de-wolf@bel.dupont.com
authors.forename: Watze
authors.initials: W
authors.lastname: de Wolf
authors.forename: Mike
authors.initials: M
authors.lastname: Comber
authors.forename: Peter
authors.initials: P
authors.lastname: Douben
authors.forename: Sylvia
authors.initials: S
authors.lastname: Gimeno
authors.forename: Martin
authors.initials: M
authors.lastname: Holt
authors.forename: Marc
authors.initials: M
authors.lastname: Léonard
authors.forename: Adam
authors.initials: A
authors.lastname: Lillicrap
authors.forename: Dick
authors.initials: D
authors.lastname: Sijm
authors.forename: Roger
authors.initials: R
authors.lastname: van Egmond
authors.forename: Anne
authors.initials: A
authors.lastname: Weisbrod
authors.forename: Graham
authors.initials: G
authors.lastname: Whale
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods / Q000592:standards*; D000827:Animal Welfare / Q000592:standards*; D000818:Animals; D004784:Environmental Monitoring / Q000379:methods*; D005399:Fishes / Q000502:physiology*; D014874:Water Pollutants, Chemical / Q000032:analysis*
chemical_list: D014874:Water Pollutants, Chemical