Newly developed chemical compounds to be released into the environment, including those used by agrochemical, cosmetic, petrochemical and pharmaceutical industries, must be subjected to stringent regulatory toxicity assessments. Currently, the potential of each chemical to induce developmental and reproductive toxicity (DART) is routinely assessed over at least two generations of rats or rabbits. Such assays require large numbers of animals, making these assessments expensive (in terms of both animals and chemicals) and time-consuming (representing an opportunity cost). We have established a simple and fast DART prediction assay using C. elegans to screen for high risk DART compounds early in the product development pipeline, which can then be eliminated from animal testing. An adaptation of the assay allows exposure to volatile compounds or those with low solubility. However, the worm's robust cuticle presents a significant barrier to chemical uptake, increasing the amount of chemical required and reducing the value of the assay for regulatory assessment. We took advantage of available mutants with altered cuticle properties to identify sensitized strains more suitable for toxicity assays. We tested
agmo-1,
bus-5,
bus-8,
bus-16 and
bus-17 for chemical permeability of their cuticle, setting this advantage in terms of chemical sensitivity against a possible reduction in physiological fitness. These criteria narrowed the candidate group down to three bus mutant strains, which were subjected to toxicity assays using a collection of hydrophilic and hydrophobic chemicals present in agrochemicals, cosmetic products, petrochemicals and pharmaceuticals, and known to cause DART in mammals. All three bus mutant strains are sensitized to chemical exposure compared to wildtype worms across a range of chemicals. With regard to our evaluation criteria and all toxicity assays, we identified
bus-5 as the ideal sensitized strain for chemical toxicity assessments that is capable of detecting DART effects at lower chemical levels, including some masked in wildtype worms, thus minimizing the probability of a false-negative outcome.