National Toxicology Program

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

The Department of Health and Human Services has published new criteria for determining whether substances can be listed as "reasonably anticipated to be a human carcinogen." The new criteria allow the determination to be made not solely on rodent research data, but on a broader scientific base that includes the known chemical structure of the substance and its effects at the cellular level.

In the Biennial Report on Carcinogens, HHS' National Toxicology Program lists substances "known to be human carcinogens" as well as substances "reasonably anticipated to be human carcinogens." Since 1981, when the report was first published, the "reasonably anticipated" list has been based on experiments in which rats and mice have been exposed to the substances in question, as well as limited human data. The new criteria will allow the listing to be based on broader and more sophisticated criteria, HHS Secretary Donna E. Shalala said.

The new criteria were developed through a collaborative process involving cancer scientists as well as consumer and industry representatives.

"Science has come a long way since the first report was published in 1981," Secretary Shalala said. "We can get a better picture today of which substances are likely to cause cancer by broadening our study to look at such things as underlying mechanisms -- the actions of substances on living cells. These broadened criteria can improve the accuracy of our scientific judgments."

In addition to the new scientific criteria, the National Toxicology Program is also creating a new process that will accommodate continuing advances in the science, and that will provide a more structured approach for listing and de-listing of substances. While few immediate changes in the list are anticipated, the new criteria and listing process represent "better science and better responsiveness," said Kenneth Olden, director of the NTP and the National Institute of Environmental Health Sciences.

Under the new criteria, even though there may not be available direct evidence that a substance causes cancer in humans, or in traditional bioassays using rats and mice, the substance still couldbe listed as "reasonably anticipated to cause cancer in humans" if there is convincing information that it works in living cells in a similar manner as other known human carcinogens.

Conversely, if a traditional two-year study shows a substance to cause cancer in laboratory rodents, the substance would not be listed if there is compelling data showing that the action or mechanism by which the cancer in laboratory animals occurred does not exist in humans.

Most of the 180 substances listed in the Biennial Report are listed as "reasonably anticipated" to be a human carcinogen and are listed based on studies performed in laboratory animals and linked to an increased incidence of malignant tumors in two or more species, or in two or more studies -- or when there are particularly unusual cancers that do not normally occur in the animals studied.

The criteria have been revised to say, "Conclusions regarding carcinogenicity in humans or experimental animals are based on scientific judgment with consideration given to all relevant information. Relevant information includes, but is not limited to, dose response, route of exposure, chemical structure, metabolism, pharmacokinetics, sensitive sub-populations, genetic effects or other data relating to mechanism of action, or factors that may be unique to a given substance. For example, there may be substances for which there is evidence of carcinogenicity in laboratory animals, but there are compelling data indicating that the agent acts through mechanisms which do not operate in humans and would, therefore, not reasonably be anticipated to cause cancer in humans.

Kenneth Olden, Ph.D., who is director of both the NTP and NIEHS, said, "With the dramatic advances in risk assessment that have been made over the past seven or eight years, it makes good sense to consider all relevant scientific data on dose response, route of exposure, chemical structure, sensitive sub-populations, data relating to mechanisms of action, and to take advantage of recent research on the molecular mechanisms responsible for chemically mediated cancers." NIEHS is one of the 17 institutes of the National Institutes of Health but NTP reports directly to the Secretary of HHS and is overseen by a board representing the regulatory agencies that use NTP data.

The original criteria for listing a substance as a known human carcinogen remain unchanged: that "there is sufficient evidence of carcinogenicity from studies in humans which indicates a causal relationship between exposure to the agent substance or mixture and human cancer."

The criteria were reviewed last year in two public meetings by the NTP Board of Scientific Counselors, by the NTP Executive Committee and by the Public Health Service's Environmental Health Policy Committee. The criteria have broad support from scientists, consumers and industry.

The review process also resulted in an expanded formal review procedure for the inclusion -- or removal -- of substances in the report. Anyone can nominate a substance to be considered for listing or delisting. All petitions received will be reviewed by the expanded process. This will include open, public meetings of the National Toxicology Program Board of Scientific Counselors' subcommittees for the Biennial Report on Carcinogens.

The new criteria were published in today's Federal Register.

Note: HHS press releases are available on the World Wide Web at: http://www.dhhs.gov.