Director: Frederick A. Beland, Ph.D.
The Division of Biochemical Toxicology conducts fundamental and applied research specifically designed to define the biological mechanisms of action underlying the toxicity of products regulated by, or of interest to, the Centers of the Food and Drug Administration (FDA). This research centers on quantifying the toxicities and carcinogenic risks associated with specific chemicals and the introduction of new techniques to enable regulatory agencies to evaluate better the risks associated with exposure to chemicals. The risk-assessment research is firmly rooted in mechanistic and exposure assessment studies focused on the understanding of toxicological endpoints, an approach that allows greater confidence in the subsequent risk assessments.
Research within the Division capitalizes on scientific knowledge in the areas of:
- Organic and analytical chemistry
- Cellular and molecular biology
- Nutritional biochemistry
- Computational risk-assessment methods
A major emphasis within the Division is to conduct research on compounds nominated by FDA for evaluation by the National Institute of Environmental Health Sciences/National Toxicology Program. This focus reflects NCTR’s superb animal facilities supported by a multidisciplinary staff of scientists with strong mechanistic-research experience, which allows subchronic and chronic toxicological assessments to be conducted in a rigorous manner to address FDA’s needs. These studies currently serve as the benchmark by which toxicological assessments are made by FDA, other federal agencies, and international regulatory bodies. In addition to providing basic information on toxicological endpoints, such as cancer, these experiments form the basis for mechanistic studies to ascertain if the response detected in the experimental model is pertinent to humans.
During 2014, Division investigators, with funding from the FDA's Center for Tobacco Products (CTP), continued experiments in animals to assess the toxicity associated with exposure to smokeless tobacco products. The endpoints being examined include the characterization of DNA adducts and metabolites arising from tobacco-specific nitrosamines, as well as molecular changes resulting from these exposures.
Division investigators, in collaboration with CDER scientists, also continued experiments with oseltamivir (Tamiflu) in support of a study sponsored by the FDA's Medical Countermeasures Initiative.
2015 Research Projects
The following list is just a sample of research projects being conducted at NCTR in the Division of Biochemical Toxicology.
- Conduct research involving the study of bisphenol A in both rodents and humans.
- Conduct pharmacokinetic investigations of bisphenol A in human subjects.
- Continue a 2-year study to investigate the toxicities of topically applied triclosan, a commonly used antibacterial and antifungal agent.
- Investigate the potential of pyrrolizidine alkaloid-protein adducts to serve as biomarkers of pyrrolizidine alkaloid exposure. This project will help characterize the risks associated with ingestion of plants containing pyrrolizidine alkaloids.
- Develop methods for the rapid detection of potential bioterrorism agents in foods.
- Investigate the role of non-genetic alterations as potential biomarkers for noninvasive evaluation of exposure to compounds of interest to FDA.
- Evaluate the correction of non-genetic abnormalities as a novel approach for personalized cancer prevention.
- Continue investigations on the pharmacokinetics—a pharmacology technique used to study the fate of substances given to an individual— of vaccine adjuvants containing squalene and α-tocopherol. These studies will assess the safety and effectiveness of these substances contained in commonly used vaccines.
- Investigate the induction of arrhythmia in induced human pluripotent stem cell-derived cardiomyocytes.
- Investigate the effects of thyroid active chemical mixtures on thyroid hormone homeostasis in pregnant women and their fetuses using computational approaches.
- Investigate the utility of animal models in determining the effects of pregnancy on the pharmacokinetics of oseltamivir (Tamiflu) in humans using computational approaches.
NCTR's Annual Report contains information on the latest accomplishments and plans for the Division of Biochemical Toxicology as well as project and publication listings.