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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.
NIEHS: Systematic Evaluation of the Application of Zebrafish in Toxicology
The small size and rapid development of the zebrafish make it a useful vertebrate model for assessing potential effects of chemicals on development in a mid-throughput to high-throughput manner. However, broader adoption of zebrafish for toxicological screening is hindered by deficits in several key areas, including consistency of experimental protocol elements; understanding of mechanisms of chemical absorption, distribution, metabolism, and excretion in zebrafish; and consistency of informatic approaches used for classification of outcomes. NTP established the Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) program, led by NTP and NICEATM scientists, to enable the broader adoption of zebrafish for toxicological screening.
In 2016, SEAZIT team members conducted a series of interviews with researchers considered to be experts in the use of zebrafish in toxicology studies. Some of these researchers, as well as data science experts, participated in an April 2017 meeting that focused specifically on how to improve zebrafish screening data analysis using ontologies. Information gathered during these discussions will be published in (1) a recommendations document that will capture best practices for data production and analysis, and identify needs to advance the application of zebrafish in toxicology, and (2) a journal article incorporating the meeting discussions within the context of a SEAZIT literature review. Findings will also inform design of an interlaboratory study designed to examine the influence of chorion removal and exposure media renewal on toxicity estimates. The study is planned to begin in 2018.