Regulatory agencies such as the Environmental Protection Agency, Food and Drug Administration, and Occupational Safety and Health Administration usually first determine whether a carcinogen exhibits linear or threshold-like dose-response behavior. Although government scientists conduct rigorous scientific reviews to evaluate everything known about a cancer-causing substance, frequently not enough information is available to distinguish between these two kinds of dose responses. In the absence of compelling evidence for a threshold-like mechanism, to protect the public health agencies assume a linear dose response. This means that any exposure, no matter how small, would carry some risk.

For carcinogens that exhibit threshold-like dose responses, other factors such as age, sex, genetic makeup, and diet are taken into consideration. When setting acceptable exposure levels of pesticides for example, the potentially greater health effects on children of pesticide residues on food are taken into consideration. Moreover, if the cancer testing is done in rats and mice, scientists consider the possibility that people are more sensitive than are rats or mice to the cancer-causing effects of a particular chemical. These factors can result in setting acceptable levels of exposure as much as 1,000 times below the level that causes a substantial increase in cancer in rodents. This approach provides a safety margin such that the acceptable level of exposure set by a regulatory agency will indeed protect the public health.

Another factor adds to the difficulty of regulating exposure to environmental chemicals: many substances that might cause cancer in people might also provide benefits to people.

Pharmaceuticals are the best example of routine benefit/risk analyses. With cancer chemotherapy drugs, we know they may be effective in treating or preventing cancer, but they also might increase the risk of second cancers developing years after the treatment. Yet cancer is often immediately life-threatening; thus the benefits usually outweigh the risks. Tamoxifen is effective in preventing the recurrence of breast cancer in many women, but also increases the risk of uterine cancer, blood clots, and strokes. The U.S. Food and Drug Administration, the National Cancer Institute, and the World Health Organization rigorously analyze the benefits and risks. They all concluded that the benefits of tamoxifen for women who have had breast cancer or for a relatively small number of women at high risk of developing breast cancer strongly outweigh the serious risks associated with the drug.

Pesticides are another example. Pesticides use has increased crop yields and has significantly benefited agricultural production. Yet concern remains over potential health effects of pesticide residues on foods consumed by humans. These potential risks are reduced by setting maximum residue levels on fruits, vegetables, and other produce and by using noncarcinogenic pesticides.

Public health officials are in the best position to identify accurately carcinogens when evidence is available from all levels—human, animal, and laboratory—but this is seldom the case. Officials often have to exercise scientific judgment and make decisions in the face of uncertainty. In these circumstances, public health agencies operate under the principle that public health protection is paramount. Decisions are debated in open public forums involving scientists from diverse disciplines and interested members of industry, environmental groups, and the public.

Public health agencies communicate this uncertainty by placing the substances in categories depending on the strength of the evidence. The categories used by the U.S. Department of Health and Human Services’ (DHHS) Report on Carcinogens are “known to be” and “reasonably anticipated to be” human carcinogens.

In the face of uncertainty, public health agencies operate under the principle that protection of public health is paramount. This means that acceptable levels of exposure are set as much as 1,000 times below the level that causes a substantial increase of cancer in laboratory animals.

Key Points

• One of the first considerations by regulatory agencies is to determine whether a carcinogen exhibits linear or threshold-like dose-response behavior.
• In the case of carcinogens exhibiting threshold-like dose responses, other factors such as age, sex, genetic makeup, and diet are taken into consideration.
• Another factor adding to the difficulty of regulating exposure to environmental chemicals is that many substances that might cause cancer in people might also have some benefits for people.
  • With cancer chemotherapy drugs, we know that while they might be effective in treating or preventing cancer, they also might increase the risk of second cancers developing years after the treatment.
  • Pesticides use has increased crop yields and has significantly benefited agricultural production. Yet concern remains over potential health effects of pesticide residues on foods consumed by humans.
• Public health officials are in the best position to identify carcinogens accurately when evidence is available from all levels—human, animal, and laboratory—but this is seldom the case. Officials often have to exercise scientific judgment and make decisions in the face of uncertainty.
• Given such uncertainty, public health agencies operate on the principle that protection of public health is paramount.
  • This means that acceptable levels of exposure are set as much as 1,000 times below the level that causes a substantial increase of cancer in laboratory animals.