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About FDA

April-June 2010

April Highlights
May Highlights
June Highlights


April 2
Cancer Research—Formaldehyde-Induced Cancers

Investigators at the National Center for Toxicological Research (NCTR) and the Hamner Institutes for Health Sciences have used a sensitive molecular method (ACB-PCR) to develop data that suggests the mechanism that causes nasal tumors in formaldehyde-treated rats likely does not involve direct-genetic damage. It has been concluded there is sufficient epidemiologic evidence that formaldehyde causes nasopharayngeal cancer in humans. Regulatory determination of safe levels of formaldehyde utilizes the rodent-cancer data and a mathematical approach based on an understanding of the mechanism of tumor formation. The high-sensitivity and quantitative nature of NCTR's ACB-PCR technology facilitates the assessment of early and rare mutational events associated with tumor formation. 

This research coupled with previous studies to assess the biological effects of formaldehyde on the rat nose will provide a scientific basis for selecting the appropriate mathematical model to assess human risk from formaldehyde exposure. A publication describing this research was recently accepted (Regulatory Toxicology and Pharmacology, 2010). 

For additional information, please contact Barbara Parsons, Ph.D., Division of Genetic and Reproductive Toxicology, FDA/NCTR.

April 9
HIV Drug Research—Translational Biomarkers

Scientists from the National Center for Toxicological Research (NCTR) and the Technical University of Lisbon have identified a sensitive biomarker of internal exposure to nevirapine in rats. Nevirapine is approved for use in combination therapy of HIV-1 infection. Despite its clinical efficacy, nevirapine administration is associated with a variety of toxic responses including hepatotoxicity, which can be fatal.

While the reason for the adverse effects of nevirapine administration are currently not clear, these studies show that nevirapine is metabolically activated to an intermediate that forms hemoglobin adducts that can be detected by mass spectrometry. The characterization of the hemoglobin-nevirapine adduct provides a relatively noninvasive biomarker of internal exposure to monitor nevirapine toxicity.

For additional information, please contact Fred Beland, Ph.D., Director, Division of Biochemical Toxicology, FDA/NCTR.

April 16
Office of Women's Health Studies

Scientists from the National Center for Toxicological Research (NCTR) presented their research results at the Office of Women's Health Breast Cancer and Mammography Seminar on April 6, 2010. NCTR's research results demonstrated that genetic variations and epigenetic inactivation of UDP-glucuronosyltransferases (UGTs) play a significant role in breast-cancer causation and treatment. The inactivation of UGTs appears to 1) enhance the sensitivity of estrogen-responsive tissues to free estrogen, thus increasing the potential risk of breast cancer; and 2) decrease the clearance of tamoxifen metabolites, thus increasing its toxicity. Genetic variations in UGTs, which result in low expression and reduced activity, have been the most studied. However, epigenetic regulation of UGTs through methylation or histone deacetylation can not only inactivate genes, but can also be reversible—having profound effects on gene expression. The epigenetic control of UGTs are being studied as a possible explanation for the higher mortality rate in premenopausal women with breast cancer in minority populations.

For additional information, please contact Beverly Lyn-Cook, Ph.D., Office of the Director, FDA/NCTR.

Stem Cell Workshop

NCTR and the Arkansas Biosciences Institute hosted a workshop on April 13, 2010, to provide an opportunity for scientists to network and establish new collaborations for stem-cell research. Following the workshop, keynote speaker Steven R. Bauer, Ph.D., Chief, Cellular and Tissue Therapies Branch, CBER, visited NCTR on April 14, 2010, to further discuss the potential of stem cells in regenerative medicine.

For additional information, please contact Amy Inselman, Ph.D., and Vijayalakshmi Varma, Ph.D., Division of Personalized Nutrition and Medicine, FDA/NCTR.


Anil K. Patri, Ph.D., Deputy Director, Nanotechnology Characterization Laboratory (NCL), National Cancer Institute (NCI), visited NCTR on April 15, 2010, to discuss the importance of physico-chemical characterization of nanomaterials in biological assessment and outcomes. As part of a continuing collaboration under a Memorandum-of-Understanding between FDA and NCI, NCTR and NCL will evaluate nanotechnology in the context of adverse-drug effects and interspecies pharmacokinetic comparisons.

For additional information, please contact Paul Howard, Ph.D., Associate Director, Office of Scientific Coordination, FDA/NCTR.

Imaging and Immunotoxicology

Scott W. Burchiel, Ph.D., Director, New Mexico Center for Isotopes in Medicine, visited NCTR on April 16, 2010, to discuss collaborations and advancements in imaging technologies and assessment of immune response following exposure to nanomaterials.

For additional information, please contact William Slikker, Ph.D., Director, FDA/NCTR.

Toxicology In Silico

Scientists from the National Center for Toxicological Research (NCTR) and the Centers for Disease Control and Prevention are presenting the results of their collaborative studies for modeling drug-drug interactions (polypharmacy) at the 2010 Toxicology and Risk Assessment Conference to be held April 26-29, 2010. The four-day meeting is sponsored by:

  • U.S. Navy, Army, and Air Force
  • Agency for Toxic Substances and Disease Registry
  • National Institute for Occupational Safety and Health
  • U.S. Environmental Protection Agency

This meeting will focus on applications of computational toxicology (COMPTOX) for improving product risk assessments. Each participating agency developed different models for predicting inhibitor activity of major drug-metabolizing cytochrome P450 enzymes. The expectation is that in silico (performed on computer or via computer simulation) technology can be used effectively as a predictive tool to identify the potential for increased or reduced effects in pharmacological activity that can occur among thousands of potential drug-drug or drug-chemical exposures in humans.

For additional information, please contact Rick Beger, Ph.D., Division of Systems Toxicology, FDA/NCTR.

April 30
FDA's ArrayTrack™ Updated with Bacterial Genome

ArrayTrack™, a bioinformatics tool developed and maintained at the National Center for Toxicological Research (NCTR), has been expanded by the addition of a Microbial Library and new data processing/visualization tools. The Microbial Library currently holds 270,000 gene records from 84 strains, including Escherichia coli, Salmonella enterica, Shigella spp., and Vibrio spp., which are common foodborne pathogens. These additions have facilitated the analysis of microarray data generated by researchers at NCTR and custom arrays developed at FDA's Center for Food Safety and Nutrition and U.S. Department of Agriculture. The data analysis demonstrates ArrayTrack™'s utility in microbial genomics research. The ArrayTrack™ platform can be a useful tool to facilitate rapid identification of enteric pathogens and their genetic traits (i.e., antimicrobial resistance, virulence, DNA fingerprints, etc.) in outbreak investigations.

For more information, contact Rajesh Nayak, Ph.D., Division of Microbiology, NCTR/FDA.

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May 7
Bioavailability of Soy Isoflavones

Investigators from the National Center for Toxicological Research (NCTR) and the University of Illinois have shown that the pharmacokinetics of bioactive soy isoflavones (e.g., serum concentrations) were identical whether administered as purified active ingredients directly into the stomach or consumed in a high-protein meal made from commercial soy-protein isolates. Manufacturers of dietary supplements and functional foods (foods that provide physiological benefits beyond nutrition) often claim, usually without supporting evidence, that their product is different from and superior to the purified active component(s). Soy-protein isolates are used in many commercial products, including soy infant formula and numerous dietary supplements (e.g., powerbars).

For additional information, please contact Daniel R. Doerge, Ph.D., Division of Biochemical Toxicology, FDA/NCTR.

Protecting the Environment

The FDA Jefferson Laboratories (National Center for Toxicological Research and the Arkansas Regional Laboratory) recycled 160 metric tons of material during the 2009 calendar year alone. Jefferson Laboratories are committed to improving their green status by pollution prevention, waste minimization, and affirmative procurement to protect the environment and employee health.

For additional information, please contact Cody Partridge, Associate Director, Office of Regulatory Compliance and Risk Management, FDA/NCTR.

May 14
Human Variome Project Meeting

Scientists from the National Center for Toxicological Research (NCTR) participated with representatives from 30 countries in the Human Variome Project (HVP) Implementation and Integration meeting and the Micronutrient Genomics Project (MGP) held at the United Nations Educational, Scientific and Cultural Organization (UNESCO) in Paris, France, on May 10-14, 2010. The meetings focused on the development of standards for sample/data collection and development of knowledge-base infrastructure necessary for the maintenance of and worldwide access to data. The HVP and the related MGP are global initiatives to facilitate the collection and sharing of information on all genetic variations/micronutrient components that affect human disease. Worldwide access to high-quality data of nutrient-gene interactions is critical for FDA's implementation of its regulatory science agenda and has the potential to greatly impact public health. This project is of special interest to the United States where the population is comprised of genetics from nearly 100 nations.

For additional information, please contact James Kaput, Ph.D., Director, Division of Personalized Nutrition and Medicine, FDA/NCTR.

May 21
Regulatory Science Research Studies Reviewed by TSSRC

The 35th meeting of the Toxicology Study Selection and Review Committee (TSSRC) was held on May 18-19, 2010, at NCTR in Jefferson, Arkansas, to discuss ongoing studies and newly proposed study designs that are part of the interagency agreement between the FDA and the National Toxicology Program/National Institute of Environmental Health Sciences (NTP/NIEHS) that support the FDA risk-assessment process.

The newly proposed studies included:

  • Oxybenzone (sunscreen)
  • Goldenseal (dietary supplement)

Ongoing studies in the following areas were discussed:

  • Food contaminants (Acrylamide, Bisphenol A, Furan, Nanoscale Silver, and Melamine)
  • Dietary supplements (Bitter Orange with Caffeine, Usnic Acid and Usnea Lichen, and Glucosamine and Chondroitin Sulfate)
  • Medical device components/contaminants (DEHP and Nanoscale Silver)
  • AIDS therapeutics
  • Antibacterial chemicals (Triclosan)
  • Permanent makeup inks

The TSSRC is comprised of regulatory scientists and subject experts from the FDA Centers and ORA, scientists from the NIEHS, and invited subject-matter experts from other government agencies, industry, and academia. The committee meets twice each year and is responsible for scientific oversight of study design and progress of ongoing work. The next meeting of the TSSRC will be held at White Oak, 10903 New Hampshire Avenue, Silver Spring, Maryland, November 16-17, 2010.

May 28
American Society for Microbiology Meeting

Scientists from the National Center for Toxicological Research (NCTR) presented their research results at the 110th American Society for Microbiology Meeting in San Diego, California, on May 23-27, 2010. The topics of their presentations included:

  • Phenotypic and genotypic methods to characterize foodborne pathogens
  • Rapid detection of antimicrobial-resistance genes and virulence factors in human clinical and environmental isolates
  • Mechanisms of antimicrobial resistance
  • Microbial interactions with host cells
  • Genomics, proteomics, and metabolomics of environmental microorganisms

For additional information, please contact Carl Cerniglia, Ph.D., Director, Division of Microbiology, FDA/NCTR.

Science Advisory Board Site Visit—Division of Neurotoxicology

A subject-matter expert subcommittee of the NCTR Science Advisory Board (SAB) and their consultants conducted an in-depth review of the current research program and future plans of the NCTR's Division of Neurotoxicology on May 26-27, 2010. FDA scientists from the Center for Devices and Radiological Health, Center for Biologics Evaluation and Research, Center for Food Safety and Nutrition, and Center for Drug Evaluation Research represented the views and comments of their respective Centers during the review process. The report of the subcommittee will be discussed at the next full meeting of the NCTR SAB. The NCTR SAB advises the NCTR Director in establishing, implementing, and evaluating the Center’s research program.

For additional information, please contact Merle Paule, Ph.D., Director, Division of Neurotoxicology, FDA/NCTR.

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June 4

In 2007, the National Center for Toxicological Research (NCTR) formalized its Science Training and Exchange Professional (STEP) Development Program to facilitate and strengthen the sharing of laboratory expertise tools and technology across the agency. During the week of May 24, 2010, reviewers from the Center for Food Safety and Applied Nutrition’s (CFSAN) Division of Food Contact Notifications participated in training at NCTR’s Division of Genetic and Molecular Toxicology. The CFSAN reviewers received hands-on experience with three genetic toxicology assays, two of which are being introduced into regulatory applications, enabling them to better evaluate data from submissions. In exchange, NCTR scientists gained a better understanding of the regulatory mandates and the types of regulatory decisions that are made in CFSAN, thus improving the utility of NCTR’s research.

For more information, contact Martha Moore, Ph.D., Director, Division of Genetic and Molecular Toxicology, FDA/NCTR.

June 11
Epigenetic Markers of Breast Carcinogenesis

Breast cancer, the most common malignancy in women, emerges through a multi-step process that involves morphological changes as the disease progresses from normal cells through distinct sequential stages: 

1) cellular hyperplasia (an abnormal increase in the number of cells)

2) carcinoma in situ (a cancerous tumor that has not invaded surrounding tissues)

3) invasive carcinoma (invasion of the tumor into surrounding tissues)

4) metastasis (spread of cancer to other organs or parts of the body).

Investigators at the National Center for Toxicological Research have demonstrated that early stages of estrogen-induced breast carcinogenesis (the process by which normal cells are transformed into cancer cells) in rats are characterized by:

  • epigenetic alterations (heritable changes that occur without changes in the DNA sequence) in global DNA methylation that alter gene expression
  • abnormal expression of proteins responsible for the proper maintenance of DNA methylation patterns
  • epigenetic silencing of the critical tumor-suppressor gene, Rassf
These results demonstrate that epigenetic alterations precede the formation of morphological changes (precancerous lesions) and indicate the significant role of epigenetic events in the induction of oncogenic pathways that leads to breast cancer. The identification of disease mechanisms such as these has the potential to aid in the early detection of breast cancer and improve the success of treatment and survivability.

For additional information, please contact Fredrick Beland, Ph.D., Director, Division of Biochemical Toxicology, NCTR/FDA. 

June 18
Joint CBER/NCTR Workshops

On June 9-10, 2010, scientists from the National Center for Toxicological Research (NCTR) and the Center for Biologics Evaluation and Research (CBER) participated in two workshops to discuss ongoing and future research as a means of fostering collaborations in microbiology and stem cell research. The Microbiology Workshop focused on current research activities at both Centers in the following areas:

  • Viruses and vaccine products
  • Microbial-host interactions
  • Probiotics
  • Anthrax pathogenesis
  • Staphylococcus aureus virulence
  • Animal models
  • Rapid detection methods

The Stem Cell Biology Workshop focused on the current state of research and regulatory needs in this area.  The Centers agreed to form a collaboration to fully characterize stem cells proposed for use as therapies in humans.  Both workshops were initiated as part of NCTR’s Science Training and Exchange Professional (STEP) Development Program and were jointly funded by CBER and NCTR.

NCTR Office Relocated

NCTR’s Associate Director for Regulatory Activities and staff have moved to the FDA’s White Oak Campus, Building 32 (2nd Floor) located at 10903 New Hampshire Avenue, Silver Spring, MD 20993.

June 25
FDA Commissioner Visits NCTR

FDA Commissioner, Margaret A. Hamburg, M.D., visited the University of Arkansas for Medical Sciences and the National Center for Toxicological Research (NCTR) on June 23-24, 2010. During her visit at NCTR, Dr. Hamburg met with senior staff, toured the facilities, led an All-Hands Meeting, and spoke at the NCTR Awards Ceremony and Luncheon.

For additional information, please contact William Slikker, Ph.D., Director, FDA/NCTR.

NTP Board of Scientific Counselors

The National Toxicology Program (NTP) Board of Scientific Counselors (BSC) met June 21-22, 2010 at the National Institue of Environmental and Health Sciences (NIEHS) to discuss several compounds of interest to the FDA. The NTP will conduct studies on the reproductive toxicity of hydroxyurea (a drug to treat sickle cell anemia) and the BSC reviewed the listing of formaldehyde and glass wool in the upcoming Report on Carcinogens, a report that is submitted by NTP to Congress. 

For additional information, please contact Paul C. Howard, Ph.D., Associate Director, Office of Scientific Coordination and FDA Liaison to NTP, FDA/NCTR.

SACATM Meeting

NCTR represented the FDA at the June 17-18, 2010 meeting of the Scientific Advisory Committee on Alternative Toxicological Methods (SACATM). NCTR representatives presented new methods (e.g., Bio-Imaging) and approaches (e.g., Zebrafish) being studied at NCTR to address toxicity issues. SACATM advises the following entities and also conducts technical evaluations of new, revised, and alternative methods with regulatory applicability and promotes new methods that refine, reduce, and replace animal testing:

  • Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM)
  • NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM)
  • Director of the NIEHS and NTP

For additional information, please contact Donna Mendrick, Ph.D., Director, Division of Systems Biology, FDA/NCTR.

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