Predictive Test Systems for Safety Evaluation Program
NIEHS is interested in:
- developing, standardizing, and validating sensitive and specific innovative tests and integrated testing strategies that can reduce, refine, or replace animal use and that will provide improved predictivity, and potential cost and time savings compared to current standard laboratory animal tests (i.e., assays for carcinogenicity, immunotoxicity, reproductive or developmental toxicity, dermal toxicity, and neuro or other organ system toxicity including acute local and systemic toxicity); and
- developing mid- and high-throughput screens and tests using phylogenetically lower animal species (e.g., insects, fish, worms) to evaluate mechanisms of toxicity to identify mechanisms of chemically-induced biological activity, prioritize chemicals for more extensive toxicological evaluation, and develop more predictive models of in vivo biological response. The proposed tests and strategies should use computational and/or biochemical models, cell/ tissue cultures, and/or animal models that are relevant to existing safety assessment databases and human experience, and that can be extrapolated to estimate risks to humans. The endpoints for these tests or assays should take advantage of the new technologies such as genomics, transcriptomics, proteomics, and bioinformatics and of novel endpoints (biomarkers) including those that are non-invasive.
Examples include but are not limited to:
- Biokinetic models that include the integration of toxicodynamic and biokinetic modeling to predict systemic toxicity.
- In vitro test methods (e.g., undifferentiated/ differentiated human/mammalian cell model systems, organotypic model systems) that can be used to predict acute and chronic toxicity by taking into account, for example, metabolism, the ability of chemicals to pass through barriers (i.e., blood brain, kidney, lung, gastrointestinal), and organ specific effects, or which allow the development of endpoints that can be extrapolated to in vivo biomarkers of toxicity.
- Alternative assays to determine dermal irritation, dermal absorption, dermal hypersensitivity phototoxicity, and ocular toxicity.
- Non-mammalian or invertebrate models for specific toxicities that utilize endpoint that are conserved across species so the results can be extrapolated to human risk.
- Use of formalin fixed, paraffin embedded (FFPE) tissues from animals and/or humans to extract RNA, miRNA or DNA for molecular profiling and toxicity classification of archival samples.
- Computational models that use data from in vivo and in vitro omics studies, in vitro mid- and high-throughput assays, and classical animal and human toxicological studies to link chemicals to genes, genes to pathways, and pathways to disease.
The NIEHS contact person is:
Daniel Shaughnessy, Ph.D. (http://www.niehs.nih.gov/research/supported/dert/sphb/staff/shaughnessy/index.cfm)
Health Scientist Administrator
Tel (919) 541-2506
Fax (919) 316-4606