NIEHS Fact Sheet #3 - NTP - 9/96

The National Toxicology Program

Not everything causes cancer. Not every chemical is a poison -- at least not in the amounts we are exposed to them. But of the thousands of chemicals that occur naturally or have been used in manufacturing, farming and our own homes and gardens, there are some bad actors.

It is the job of the National Toxicology Program, headquartered at the National Institute of Environmental Health Sciences, to find them.

NTP works to improve the data on which federal regulatory agencies make decisions -- and to improve the quality of risk assessment. NTP works with the regulatory agencies, and with industry, consumer groups and others to determine the most likely candidates for concern -- and to have them tested. Hundreds have been tested. (NTP and NIEHS conduct or support about a third of all toxicology studies worldwide.) Some substances, after testing, have been banned by government agencies or restricted by industry. For example:

• methylene chloride, used to decaffeinate coffee, has been replaced by a water process

• various food additives and dyes have been restricted or eliminated by the Food and Drug Administration following NTP tests showing adverse effects

• dichlorvos, used for flea collars and "no pest" strips, was found carcinogenic in animals in 1991, and was barred from these uses by the Environmental Protection Agency. A 1995 study (done elsewhere) confirmed the link between dichlorvos exposure and human cancer, in this case leukemia.

• benzene, a gasoline additive, is no longer used in consumer products, because of evidence it can cause cancer.

Substances that did not prove carcinogenic include such commonly used prescription drugs as penicillin and erythromycin. What a relief! In fact, when scientists at the National Toxicology Program tested compounds that were used in large quantities, less than 10 percent proved carcinogenic.

Substances tested by NTP, along with others on which NTP has gathered data, are listed -- when the evidence warrants -- in the Biennial Report on Carcinogens, which is submitted to Congress and made public by the Secretary of Health and Human Services.

NTP also generates and collects test results on problems other than cancer, such as genetic and reproductive toxicity, birth defects and impairment of the brain and nervous system.

Alternatives to animal tests: The current "gold standard" for testing a chemical to determine if it is carcinogenic is the two year bioassay in male and female rats and mice. While the testing itself takes two years, the planning of the tests and their evaluation and review take the process to about five years, at a cost of $2-4 million or more.

NTP and NIEHS hope to cut the costs, reduce the number of rodents used and shorten the time required for tests. It has explored alternative testing methods, such as tissue cultures, and sponsored meetings designed to lead to international agreement on validating and using other test methods.

One of the most promising alternatives are mice that have been genetically modified to react more quickly to carcinogens. Their use -- if shown to be as discriminating as current testing -- would reduce the numbers of rodents required, as well as reducing the money and time required for testing. Two lines of gene-modified, or transgenic, mice have been identified by NIEHS/NTP scientists as good candidates for a new, standard test. (The lines are the p53 deficient line developed at Baylor University and the Tg.AC line developed at Harvard.) Chemicals that have already been reviewed using the currently standard two-year biosassays are now being reviewed by NIEHS/NTP in transgenics to see if the results are the same and the information as complete.

Initial contacts have been made with representatives of chemical and drug industries and of Japanese and Dutch institutions with experience with transgenic mouse lines. NTP is encouraging a broad partnership that will work for a new, standard test.

The National Toxicology Program has the same director as NIEHS, Kenneth Olden, Ph.D., but he reports on NTP matters to the Secretary of Health and Human Services. That is because the National Toxicology Program has a broad charter to test on behalf of not only NIH and the NIEHS but the Food and Drug Administration, the Centers for Disease Control and Prevention's National Institute for Occupational Safety and Health, and the Agency for Toxic Substances and Disease Registry. Beyond the Department of Health and Human Services, the Occupational Safety and Health Administration, the Environmental Protection Agency and the Consumer Product Safety Commission have interests in the results -- and they also have representatives on the executive committee that provides oversight of the toxicology program. Besides these governmental organizations, consumer groups, businesses, unions and individuals can nominate substances to be tested.

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NIEHS Fact Sheet #3 - NTP - 9/96
NTP liaison office: 919/541-0530

 Additional Information:

• National Toxicology Program