April 6, 2001
PLANNED NATIONAL TOXICOLOGY PROGRAM STUDIES ON HEXAVALENT CHROMIUM
National Toxicology Program (NTP)
The Department of Health and Human Services established the NTP in 1978 and charged the NTP with coordinating toxicological testing programs within the Public Health Service of the Department; strengthening the science base in toxicology; developing and validating improved testing methods; and providing information about potentially toxic chemicals to health regulatory and research agencies, scientific and medical communities, and the public. In its 23 years, the NTP has become the world's leader in designing, conducting, and interpreting toxicology studies. The NTP is an interagency program whose mission is to evaluate agents of public health concern by developing and applying the tools of modern toxicology and molecular biology. In carrying out its mission, the NTP has several goals to:
· provide evaluations of substances of public health concern,
· develop and validate improved (sensitive, specific, rapid) testing methods,
· develop approaches and generate data to strengthen the science base for risk assessment, and
· communicate with all stakeholders including government, industry, academia, the environmental community, and the public.
NTP Toxicology and Carcinogenesis Studies
The NTP carries out studies to characterize and evaluate the toxicologic potential, including carcinogenic activity, of substances of public health concern. Substances selected for NTP toxicology and carcinogenesis studies are chosen mainly on the basis of human exposure, potential for toxicity, and availability of data. These bioassays are generally conducted through repeated administration of the substance to groups of laboratory animals (usually rats and mice of both sexes) for up to two years. The results from these bioassays are peer-reviewed by the NTP Board of Scientific Counselors Technical Reports Subcommittee, an external scientific panel, and published as NTP Technical Reports; they may also be published in peer-reviewed scientific journals. The NTP has performed over 500 rodent carcinogenesis bioassays.
Examples of Recent NTP Rodent Carcinogenicity Studies Include:
Naphthalene (Technical Report No. 500)
Naphthalene has many important chemical manufacturing uses and is also used in mothballs and bathroom deodorizers. The NTP two-year bioassay found clear
evidence of carcinogenic activity of naphthalene based on an increased incidence of tumors in the nose of male and female rats. The rats in this study were exposed by inhalation, just as most people are, in doses comparable to some human workplace exposures. Previous NTP inhalation studies were also positive. This chemical was nominated to the NTP by the National Institute for Occupational Safety and Health and the Occupational Safety and Health Adminstration and should have direct bearing on safety levels to be established by these agencies.
p,p’-Dichlorodiphenyl Sulfone (Technical Report No. 501)
p,p’-Dichlorodiphenyl sulfone is used as a starting material in the production of polysulfones and polyethersulfones, as a component in reactive textile dyes, and is also a by-product of pesticide production. The NTP two-year bioassay found no evidence of carcinogenic activity of p,p’-dichlorodiphenyl sulfone in male and female rats and in male and female mice. This chemical has been found in humans and in fish; the results of the NTP studies lessen the concern over human exposure to this chemical.
NTP Study on Hexavalent Chromium
While the toxicity and carcinogenicity of hexavalent chromium compounds have been recognized for some time, adequate long-term oral toxicity studies are largely unavailable and there remain gaps in our collective knowledge regarding the potential health risks. In October 2000, California State Senator Schiff, seeking definitive data on whether hexavalent chromium is carcinogenic to humans who consume contaminated drinking water, nominated carcinogenicity testing of hexavalent chromium to the NTP. The NTP immediately began to evaluate the literature and determine the need for further studies. In February of this year, senior officials at the California Environmental Protection Agency and the California Health and Human Services also nominated hexavalent chromium administered in drinking water to the NTP for carcinogenicity studies. In March 2001, members of the California Congressional Delegation (including newly elected Congressman Schiff), also nominated hexavalent chromium administered in drinking water to the NTP for carcinogenicity testing. Based on the urgency of these requests from California and the need to address these public health concerns, NTP plans studies on hexavalent chromium. The NTP will begin designing long-term (2-year) rodent toxicology and carcinogenicity studies of a representative hexavalent chromium compound administered in drinking water, and immediately initiate shorter-term toxicity studies to aid in designing and interpreting the long-term studies. Other auxiliary studies aimed at improving our understanding of the bioavailability, distribution, and mechanisms of toxicity of hexavalent chromium in the context of the long-term studies will also be considered.
The NTP has a formal multi-step process for reviewing all nominations that are submitted to the Program before nominated substances are selected and studies are designed and implemented. This multi-step process provides the NTP with appropriate direction and guidance and ensures that relevant scientific and public concerns are addressed when considering substances for study. Of paramount consideration in this review process and in the NTP's decision making is the public health significance of any requested studies, the availability of adequate existing toxicological data, and the extent of human exposure. The review process for hexavalent chromium has a few more steps, and the NTP will seek broader input into the nomination and design phase of these studies over the next few months. This input will be valuable as the NTP moves forward with the long-term cancer studies.
National Institute of Environmental Health Sciences (NIEHS)
The NIEHS is the lead agency for the NTP and Dr. Kenneth Olden, Director, NIEHS, also serves as the NTP Director. The NIEHS is one of the National Institutes of Health and its primary mission is to reduce the burden of human illness and dysfunction from environmental exposures. Human health and human disease result from the interaction of our environmental exposures and our individual susceptibilities over time. The NIEHS achieves its mission through multidisciplinary biomedical research programs conducted in its own laboratories and supported in laboratories around the country, prevention and intervention efforts, and communication strategies that encompass training, education, technology transfer, and community outreach.
For questions or comments please contact:
Dr. Christopher Portier, Acting Associate Director
National Toxicology Program
Phone: 919-541-0530