ICCVAM Biennial Report 2014-2015

Pesticides, food additives, drugs, and other substances are tested for their potential to cause reproductive or developmental toxicity. Reproductive toxicity tests assess a substance’s tendency to cause reproductive system effects, while developmental toxicity testing evaluates the extent to which exposure to a substance may harm a developing embryo or fetus.

Reproductive and developmental toxicity tests are required by multiple regulatory agencies and can use large numbers of animals. The complexity of these endpoints makes it unlikely that any single alternative test method will serve all regulatory needs. ICCVAM agencies are working with regulatory and industry partners to explore alternative tests that can be used in combination to provide the information needed to make accurate developmental and reproductive safety assessments.

ICCVAM Agency Activities

• National Institute of Environmental Health Sciences: NICEATM is working with other National Toxicology Program scientists to establish a list of reference chemicals for use in validation studies of alternative test methods for developmental toxicity. The list is being constructed with input from experts from industry, academia, and government and is expected to include a broad variety of chemicals, including agrochemicals and pharmaceuticals, that have been shown to have either positive or negative activity in clinical pharmaceutical studies or high-quality in vivo developmental toxicity studies in rodents or rabbits. The identified reference chemicals will be candidates for evaluating the performance of in vitro assays based on primary cells, stem cells, or cell lines, as well as in vivo assays using lower order organisms such as zebrafish or the roundworm Caenorhabditis elegans.
• National Institute of Environmental Health Sciences: NICEATM scientists participated on the management team for a validation study coordinated by the Japanese Center for the Validation of Alternative Methods to evaluate the Hand-1 luciferase assay, which measures toxicity to mouse embryonic stem cells to identify potential developmental toxicants. Laboratory work on the study is ongoing.