High-Throughput Toxicity Screening with C. elegans: Current Platforms, Key Advantages, and Future Directions

Nematodes, including the model Caenorhabditis elegans, pose many advantages for high-throughput screening (HTS) of chemical toxicity, such as ease of culture, short life cycles, low maintenance costs, and a wide array of available strains and mutants. Several HTS platforms have already been developed to rapidly assess multiple endpoints, including behavior, growth, and reproduction of C. elegans. Here, we summarize the available methodologies for HTS in C. elegans and evaluate their strengths and limitations for routine chemical screening. We also assess the relationship between C. elegans HTS data and toxicity information from other common surrogate species, including fish, invertebrates, and algae, as well as data from other HTS assays. Notably, image-based HTS data yielded strong concordance between toxicological endpoints for C. elegans and established ecotoxicological surrogates. Finally, we make recommendations for how to improve existing platforms and where collaboration and investment are needed to make nematodes an integral part of the battery of alternatives to reduce vertebrate testing.