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NIEHS News
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Biennial Report on Carcinogens
The National Toxicology Program Board of Scientific Counselors met in a public session at NIEHS on 6 April 1994. The board, predominantly composed of scientists from outside government, is the principal body providing scientific oversight and review to NTP. A major agenda item was the proposal that the board play a role in reviewing the criteria for inclusion of substances in the Biennial Report on Carcinogens (formerly the Annual Report on Carcinogens) as well as in reviewing chemicals, substances, and processes nominated for upcoming editions.
The board adopted a resolution that a new subcommittee of the board should be created to review the biennial report. The subcommittee should include selected members of the board, ad hoc reviewers, and liaison members from the NIEHS and other agencies. The new subcommittee should begin by convening a working group to review the criteria for listing in the biennial report. The NTP board should approve the work of the subcommittee.
NIEHS, UNC and Duke Instate Training Program
In July 1993, NIEHS entered into 10-year contracts with the University of North Carolina at Chapel Hill School of Medicine and Duke University Medical Center for collaboration in clinical research and training. Recently NIEHS and the universities instated a training program for physicians and nurses in environmental clinical sciences. The program will provide a two- to three-year program in environmental medicine, the study of diseases and other conditions related to exposure to physical and chemical agents.
Duke and UNC will coordinate the training as a single program under an advisory board of members representing all three institutions. Trainees will be based at either university, depending upon the trainee's primary clinical interests and preference. To avoid duplication, certain training elements may be offered at only one medical center. At the outset, two physicians and one nurse will be accepted as trainees at each university. Split or paired fellowships are possible for those who wish less than a full-time commitment.
During the first year, trainees will take graduate courses on topics such as research design, epidemiology, statistics, pharmacology, toxicology, occupational health, and ethics. They will spend at least one year, usually the second in a two-year program, at a branch or laboratory of NIEHS working with an experienced investigator who will serve as a scientific mentor, along with clinical investigators at Duke and UNC. A trainee's program for a third year will be extended to allow a second year in the laboratory, if needed, at the request of the trainee with the approval of the principal investigator, mentor, and training advisory board.
Those selected for the program must be U.S. citizens. Physicians must have at least one year post-medical training, be licensed or eligible for licensure in North Carolina, with board eligibility strongly recommended. Because there is no single medical discipline that covers all aspects of basic and clinical environmental health science, physicians may be chosen from any medical discipline. Nurses must have a bachelor's or master's degree, be eligible for licensure in North Carolina, and have at least one year of clinical experience.
Interested physicians should contact either Eugene P. Orringer, UNC Hospital School of Medicine, (919) 966-1435, FAX (919) 966-1576; or Edward L.C. Pritchett, Duke University Medical Center, (919) 684-6720, FAX (919) 681-7918.
Interested nurses should contact either: Carol F. Baker, Nursing Education and Research, UNC Hospital School of Medicine, (919) 966-1435, FAX (919) 966-1576; or Barbara Turner, School of Nursing, Duke University Medical Center, (919) 684-3786, FAX (919) 681-8899.
NTP Liasion Office
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Sandra Lange. New director of NTP liaison office will work to strengthen communication and collaboration. |
Sandra Lange has been named director of the newly established NTP Liaison Office. "The establishment of the NTP Liaison Office is a further effort to strengthen our communication and working relationships with state and local governments; with other agencies within the federal government, industry, labor, academia, and all segments of the public," said Kenneth Olden, NIEHS director. Lange accepted the directorship of the new office after serving as director of the NIEHS Office of Communications. Lange is a member of the NIEHS Executive Committee and will work within the office of George Lucier, acting director of the Environmental Toxicology Program.
Founded in 1978, the National Toxicology Program coordinates toxicology studies and methods research, development, and validation within the Department of Health and Human Services, under the Assistant Secretary of Health. In 1978, the NTP built upon the Bioassay Program of the National Cancer Institute and has continuously broadened the scope of toxicological studies to include multiple toxicological disease endpoints in addition to tumors. NTP encompasses of the National Institutes of Health's NIEHS and the National Cancer Institute, the Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health, and the Food and Drug Administration's National Center for Toxicological Research.
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At the helm. (left to right) Deputy Program Director John Bucher and Acting Director George Lucier of the Environmental Toxicology Program are guiding the NTP in new directions. |
NTP has published a series of technical reports, which summarize two-year, both gender, two-species (rats and mice) studies of more than 400 chemicals. NTP staff has published extensively in scientific journals reporting toxicological studies and methods development and validation.
The purpose of the new NTP Liaison office is to increase public awareness of NTP's research, new directions, and priorities, and broaden both working relationships and dialogue with the many constituencies with interests related to the NTP. An early priority will be increasing input to the NTP nomination and selection process. NTP seeks nominations of high-priority chemicals or other environmental agents of public health concern, as well as nominations of chemical issues in need of further study. Inquiries relating to the NTP may be made to Sandra Lange, National Toxicology Program Liasion Office, PO Box 12233, MD A2-01, Research Triangle Park, NC 27709, (919) 541-0530, FAX (919) 541-0295.
Olden Announces Initiatives
Kenneth Olden, NIEHS director, has identified 35 priority areas as NIEHS initiatives. These initiatives will receive the attention of senior management at NIEHS. The initiatives are programs that NIEHS has undertaken over the past two years that are targeted for special monitoring and development. Each initiative has been assigned to one or more members of the NIEHS executive committee or other members of senior staff for day-to-day management and long-term planning. The assigned persons will present goals and objectives, both short and long term, and parameters that will be used to monitor their particular programs.
Olden emphasized that these 35 initiatives in no way diminish the institute's commitments to other areas of research. Rather, the initiatives have been identified to give special focus in priority areas where it is thought that expanded, coordinated efforts will be effective.
The NIEHS initiatives will be highlighted in summaries in NIEHS News in coming issues of EHP, beginning this issue with an article on mechanistic toxicology and risk assessment in the National Toxicology Program. A list of all 35 initiatives, which include agricultural chemicals, global climate change, women's health, and lead and other metals, will be published in a future issue of EHP.
NIEHS/NTP Initiatives
National Toxicology Program and Risk Assessment
The National Toxicology Program has broad responsibilities for expanding the toxicological database on the impact of chemical interactions with biological systems, providing data that strengthen the scientific foundation for regulatory decisions, developing and validating alternative test systems, and communicating strategies and findings to the scientific community, regulatory agencies, and the public. NTP strategies and approaches are evolving in a number of ways to meet these responsibilities and to take advantage of the emerging opportunities presented by the tools of molecular biology.
The overall objective of NTP initiatives is to protect public health by more efficiently testing chemicals for toxic effects using a broad array of test systems and by generating data that can make risk assessments more reliable. Current risk assessment approaches frequently use default assumptions which reflect an inadequate scientific foundation for assessing risk.and create an unacceptable amount of uncertainty. This uncertainty can lead to both over- and under-regulation. The costs of regulatory decisions are enormous in terms of industry compliance, health costs, and litigation, yet relatively little money is spent to develop strategies for reducing uncertainties in risk assessment.
Traditional toxicity tests such as the two-year chronic bioassay to detect carcinogens have been the basis for most regulatory decisions regarding the safety of environmental chemicals. However, only a limited number of the thousands of chemicals present in the environment, for which we have little or no toxicological data, can be studied by these conventional approaches. Increased application of knowledge of the mechanisms of toxicity can help in several ways.
First, hazard identification, which is currently done using animal bioassays to determine whether an environmental agent has the potential to produce an adverse health effect, can be streamlined by appropriate use of mechanistic information. The emerging tools of molecular biology, which can characterize interactions of chemicals with critical target genes, offer tractable approaches for developing more accurate and inexpensive methods to perform this step. Examples include methods for detecting receptor-mediated toxicants, use of transgenic animals, and other alternative/complementary in vivo tests to the rodent bioassay. Promising mechanistic and predictive methods to identify environmental health risks must be developed, validated, and accepted for regulation. These approaches could dramatically increase the number of environmental agents evaluated for toxicity. Although mechanistic approaches should be more frequently incorporated into toxicity testing, the chronic bioassay in rodents must be used in many cases, especially those where mechanistic data are not available and when validating new methods. A variety of sources will be used for this approach, including grants, contracts, interagency agreements, and intramural research.
Second, assessment of the difficult and controversial issue of dose-response relationships must be refined. Data from experimental animals are usually obtained with relatively high doses of chemicals because of limitations in resources and attempts to reduce the number of animals used. This practice requires the extrapolation of health effects to exposure levels in humans much lower than those for which experimental data are available. Depending on the method of extrapolation used, risk estimates may vary by several orders of magnitude. Although regulatory decisions on potentially hazardous environmental agents should not be delayed, rather than use default assumptions, biologically based models need to be applied when appropriate. These models should be based on quantification of critical molecular lesions over a wide dose range. The relevance of a model can best be determined when mechanistic data are available that permit rational comparisons between observed effects in experimental animals and expected effects in humans.When using mechanistic approaches in bioassays, dose selection must be developed to maximize the potential for deriving dose-response relationships. Effective use of biologically based models on a wide scale will require an intense effort to refine and develop methods for translating complex biological data into mathematical terms suitable for risk assessments. These approaches need to be reviewed and accepted by both the scientific and regulatory communities.
More research on comparative mechanisms of toxicity should focus on both rodent and nonmammalian test systems and be directed at the development of more rapid and less expensive tests. Mathematical risk assessment models are often criticized for inadequate linkage to real biological systems. Improvements in model development will require use of the emerging computational graphics technologies and evaluation of models by multidisciplinary groups composed of biologists, mathematicians, epidemiologists, and regulatory officials.
Third, although a great deal of data may be available for occupational exposures to toxic chemicals, information on human exposure to these same chemicals in the general environment is often inadequate and must be improved. Increasing knowledge of the mechanisms responsible for environmentally induced disease, coupled with the development of sensitive and specific tests to monitor the presence of a chemical in the body or an early biological effect of that chemical, offer opportunities to monitor low-level human exposures. Validated exposure markers should be applied to determine the human burden of chemicals and their possible health consequences. In addition, the development of new tests needs to be encouraged, as well approaches to validate these promising new tests.
Continued research to enhance our knowledge of gene-environment interactions is needed. Humans vary widely in their response to pharmaceuticals, lifestyle factors, and environmental agents. For example, some people who smoke cigarettes get cancer but many don't, and some people have adverse effects from drug therapies whereas others don't. The biological bases for these variations in response are now being discovered. Of particular importance are inherited genes that predispose an individual to an adverse health outcome when exposed to certain classes of chemicals. It is now possible, in some cases, to test individuals or populations for "at-risk genes" and determine the range of expected variation in response. When this information is available, it should be used in risk assessments rather than default methodologies. In some cases, the range of responses will be much greater than the default 10-fold ranges.
The major purpose of toxicity testing and risk assessment should be prevention of adverse effects by establishing scientifically valid safe exposure levels. NIEHS and NTP are attempting to integrate mechanistic data, human data, toxicity test data, and biomathematics to strengthen the scientific foundation on which risk assessments are based. Effective and timely communication with regulatory agencies, the scientific, environmental, and industrial communities, and the public is an integral part of this effort. For information, contact George W. Lucier, acting director, ETP, (919) 541-3802, FAX (919) 541-3647. |
ERRATA
In the NIEHS News section of the January 1994 issue of EHP, an announcement appeared describing NIEHS efforts to establish a toll-free environmental health clearinghouse. Assistance in identifying appropriate sources of information was requested; however, an incorrect address was provided. Please address information to Finis Cavender, Information Ventures Inc., 100 Capitola Drive, Suite 108, Durham, NC 27713, (919) 361-0570, FAX (919) 361-9408.
Last Update: July 30, 1998 |
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