About the Division
Improve public health by providing FDA with the expertise, tools, and approaches necessary for the comprehensive assessment of genetic risk.
- Respond to Agency needs for expertise and chemical-specific data (e.g., nanomaterials, tobacco products, drug impurities).
- Maintain DGMT’s tradition of leadership in regulatory assay development and validation (e.g., MLA, Hprt, MN, TGR, miniAmes, Pig-a, in vitro organotypic models).
- Develop better methods for carcinogenicity testing and translation of rodent studies to human risk (e.g., CarcSeq)
- Develop advanced in vitro toxicological models that incorporate genotoxicity endpoints (e.g., human ALI airway model)
- Engage FDA product centers, National Toxicology Program, and other national and international organizations to set research priorities.
- Develop better biological models for assessing human risk (e.g., airway and testes organotypic in-vitro models, liver spheroids).
- Develop more comprehensive approaches for monitoring genetic variation: ec/eaNGS (error-corrected/error-avoidance Next Generation Sequencing).
2022 Select DGMT Accomplishments
Guidelines for Conducting Rodent Erythrocyte Pig-a Assay
DGMT scientists led a multinational consortium in drafting a Test Guideline (TG) for conducting the rodent erythrocyte Pig-a gene mutation assay. The assay is used by the FDA to evaluate the carcinogenic hazards of regulated substances. DGMT provided recommendations in 2021, which cleared the way for the TG to be published in June 2022 by the Organization for Economic Co-operation and Development. This guideline will ensure that data submitted for regulatory safety assessments of most FDA-regulated products are of uniformly high quality.
Mutation Analysis Using Error-Corrected Next Generation Sequencing
Error-corrected Next Generation Sequencing (ec-NGS) is a potentially powerful approach for evaluating rare mutations directly by the changes they make in the DNA sequence of the genome. Mutation is used by the FDA in safety evaluations of regulated products as a biomarker of carcinogenicity. DGMT scientists successfully conducted ec-NGS analyses in bacteria, C. elegans, and mammalian cells, including the cells from an organotypic tissue model, using two platforms — Duplex Sequencing and PacBio HiFi Sequencing.
DGMT scientists are frequently asked to consult in evaluating genetic toxicology data and have hands-on expertise in conducting common regulatory genetic toxicology assays (e.g., Ames, TGR, Comet and Pig-a).
Ongoing DGMT Research Projects in 2023
- Evaluate high-content high-throughput genetic toxicology using metabolically active hepatic cell lines and primary hepatic cells from humans
- Analyze genetic toxicology using a panel of 14 human cell lines, each expressing a different human drug metabolizing enzyme
- Evaluate mutagenicity of drug impurities in support of the Center for Drug Evaluation and Research Nitrosamine Drug Impurity Task Force
- Validate study of vitrocell exposure systems to investigate the in vitro toxicity of electronic nicotine delivery systems at the air-liquid interface of human airway tissue models
- Develop an in vitro system to evaluate the disease-related toxic effects of inhaled aerosols and vapors in human airway tissue models
- Develop an in vitro co-culture system to test the adverse effects of drugs and their metabolites on human embryo-fetal development
- Develop a microphysiological system for evaluating Zika Virus sexual transmission using a testicular model
- Develop a microphysiological system for evaluating antibody therapies targeting viral infections during pregnancy: a Zika Virus case study
Resources For You
- DGMT Fact Sheet
- NCTR Annual Reports
- Meet the Principal Investigators
- About the National Center for Toxicological Research
- National Center for Toxicological Research
Food and Drug Administration
3900 NCTR Rd
Jefferson, AR 72079
- (870) 543-7121