Biochemical Toxicology

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 gene-nutrient interactions and the introduction of new techniques to assess toxicities and carcinogenic risks. The risk-assessment research is firmly rooted in mechanistic 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 biochemistry, organic chemistry, analytical chemistry, cellular and molecular biology, nutritional biochemistry, toxicology, phototoxicology, and pharmacology.

A major emphasis within the Division continues to be conducting research on compounds nominated by FDA for evaluation by the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP). 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 and other federal agencies. 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.

Ongoing Research Projects

• A Toxicological Evaluation of Nanoscale Silver Particles in Rodents (E0217001)
• Assessment of the Nephrotoxic Effect of a Combined Exposure to Melamine and Cyanuric Acid (E0216901)
• Assessment of the Nephrotoxicity of a Seven-Day Combined-Exposure to Melamine and Cyanuric Acid (E0731701)
• Benzocaine-Induced Methemoglobinemia in an Acute Rat Model (E0730201)
• Bioassays in the Fischer 344 Rat and the B6C3F1 Mouse Administered Aloe Vera Plant Constituents in the Drinking Water (E0214201)
• Carcinogenicity of Acrylamide and its Metabolite, Glycidamide, in Rodents: Neonatal Mouse Bioassay (E0718501)
• Chemical Inactivation of Protein Toxins on Food Contact Surfaces (E0730301)
• Detection of DNA Adducts in Mice Treated with Benzo[a]pyrene at Low-Exposure Levels (E0723701)
• Determination of Carcinogenic Mechanisms for Furan in Fischer 344 Rats (E0216401)
• Development of a PBPK/PD Model for Acrylamide (E0721201)
• Di(2-ethylhexyl)phthalate (DEHP) Toxicokinetics in Neonatal Male Rhesus Monkeys Following Intravenous and Oral Dosing (E0216001)
• Dietary Modulation of the Renal Toxicity of p-nonylphenol (NP) and di(2-ethylhexyl)phthalate (DEHP) (E0714201)
• DNA Adducts of Tamoxifen (E0701101)
• Effect of Soy-Containing Diets on Ammonium Perchlorate-Induced Thyroid Toxicity in Sprague-Dawley Rats (E0716301)
• Effect of Topically Applied Skin Creams Containing Retinyl Palmitate on the Photocarcinogenicity of Simulated Solar Light in SKH-1 Mice (E0214301)
• Effect of Urinary pH upon the Nephrotoxicity of a Combined Exposure to Melamine and Cyanuric Acid (E0731501)
• Effects of Sedatives on the Metabolism of Di(2-ethylhexyl)phthalate (DEHP) Administered by Intravenous Injection and the Relationship of DEHP Metabolism to Biological Effects in Neonatal Rats (E0216201)
• Evaluation of the Toxicity of Bisphenol (BPA) in Male and Female Sprague-Dawley Rats Exposed Orally form Gestation Day 6 through Postnatal Day 90 (E0217201)
• Genotoxicity and Carcinogenicity of Acrylamide and its Metabolite, Glycidamide, in Rodents-Rangefinding/Subchronic/Two-Year Chronic Carcinogenicity Studies (E0215001)
• Global and Locus-specific DNA Hypomethylation: A Common Mechanism Involved in Genotoxic and Non-Genotoxic Rat Hepatocarcinogenesis (E0718101)
• Human Studies of Isoflavone Safety and Efficacy (S00607)
• Inactivation of UDP-Glucuronosyltransferases in Human Breast Tissues: Accessing Cancer Risk, Tamoxifen Safety and Toxicity (E0734001)
• Ketamine Pharmacokinetics in Children (E0726201)
• Laboratory Studies in Melamine and Cyanuric Acid Biochemical Toxicology (E0729101)
• Liver Toxicity Biomarkers Study: Phase 1, Entacapone and Tolcapone (E0726601)
• Mechanisms of Nevirapine Carcinogenicity (E0217101)
• Method Development for Study of Antioxidant Properties in Dietary Supplement (E0730501)
• Perinatal Carcinogenicity of Drug Combinations Used to Prevent Mother-to-Child Transmission of HIV (E0214111)
• Photoinduction of Cutaneous Malignant Melanoma in TP-ras/ink4A (+/-) Transgenic Mice (E0708901)
• Phytoestrogens and Aging: Dose, Timing, and Tissue (E0721001)
• Real-Time PCR Assays for Ricin and Related Potential Bioterrorism Agents in Foods (P00684)
• The Role of Perinatal Development on Toxicokinetics of Bisphenol A (E0216701)
• Thermodynamic Measurements for Inactivation of Bioterrorism Agents Ricin and Abrin (P00708)
• Two-Year Carcinogenicity Bioassay of Furan in F344 Rats (E0216801)
• Use of Electron Spin Resonance Spectroscopy to Characterize the Interactions Between Nanoscale Materials and Model Biological Systems (E0730601)

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.