Fish and Amphibian Assays’ Strengths and Weaknesses

Strengths:

The advantages of the screens discussed here are that they are conducted in a physiologically intact vertebrate system.  The endocrine system is complex, and this tier captures some of this complexity.  Thus instead of testing specific cells or tissues, one can see chemical effects on a whole animal.

By testing effects on animal development during the earliest life stages, the probability of capturing an adverse effect is markedly heightened. Because fish reproduce in great number and develop quickly, one can do many assays on many individuals, thus giving a clearer result. Stages of development are much shorter than in mammals, and access to embryos for manipulation and observation is easier because they are not in a womb.

Another strength of the fish assays is that scientists have made significant progress in automating the assays, moving partially toward a version of high-throughput screening approaching the high throughput cell-based assays which might be deemed “medium-throughput assays.” This will lead to cheaper, faster and more accurate assays.

Limitations:

Disadvantages arise from the fact that, while we can learn a lot from them, fish and amphibia obviously are not mammals, and as such cannot provide all the answers that one might want about the potential human-relevant endocrine activity of a given compound.

Another disadvantage is that, while these assays can give an excellent overview of potential toxic effects, they are less good at explaining why these effects occur.  For the chemist who wants to know the specific mechanism by which a chemical is endocrine-active in order to re-design that chemical to make it benign, tests at the mammalian level, and/or specific tests at the cellular level, would be needed.