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.

Assessment of an approach to estimating aquatic bioconcentration factors using reduced sampling

“…These studies are demanding of resources and require the use of large numbers of animals. Because of the very large number of chemicals that need to be tested, there is a need for methods for estimating the BCF that require fewer animals and resources [5]. In vitro tests [6–9] and modeling [10,11] of the uptake and metabolism of xenobiotic chemicals are of great interest and promise to reduce the need for in vivo testing in the future.…”

Critical Review of Read‐Across Potential in Testing for Endocrine‐Related Effects in Vertebrate Ecological Receptors

“…However, animal toxicity testing is costly and time consuming. Given the impracticality of using animal tests to assess the large number of chemicals in commerce on multiple types of organisms, and the global initiative toward replacement, reduction, and refinement of animal testing (Russell and Burch 1959; De Wolf et al 2007), alternative approaches are required. Methods based on biological read‐across for species extrapolation may be advantageous in assessing taxonomic susceptibility and prioritizing further testing.…”

Bioconcentration, Metabolism, and Spatial Distribution of14C‐Labeled Laurate in the Freshwater AmphipodHyalella azteca

“…Even though such experiments are well established, they usually require many (>100) laboratory animals, may last several weeks, and are costly. Ethics of animal testing are intensively discussed, especially in view of the 3‐R principles (de Wolf et al ; Russell and Burch ). Thus, alternative test methods would be of value.…”