Does Nitrite Cause Cancer? Concerns About Validity of FDA-Sponsored Study Delay Answer
HRD-80-46: Published: Jan 31, 1980. Publicly Released: Jan 31, 1980.
- Full Report:
A recent study conducted for the Food and Drug Administration (FDA) indicated that nitrite may cause cancer. Legislation provides that any substance determined to cause cancer in humans or animals may not be used as a food additive. This same legislation also states that a substantial unresolved question about the safety of a food additive is also a basis for its removal from use. For several years, nitrite has been used to preserve, color and flavor meat, poultry, and fish. It also protects against the formation of botulism toxin. FDA and the Department of Agriculture (USDA) are faced with a regulatory dilemma in that the use of nitrate protects consumers against one serious problem, and may cause another. Because nitrite is widely used, is important, and lacks an acceptable chemical substitute, FDA, with USDA concurrence, planned to phase out its use over several years. However, the Department of Justice determined that no authority exists for such a phase out and that removal of a cancer-causing substance may not be delayed.
Questions have been raised about the validity of the nitrite study. Site visits to the researcher's laboratory were to be used to assess contractor performance, but this was not done until a critical phase of the study was nearly completed. When progress reports, the primary tool for monitoring the study, were submitted late or not at all, agency officials did not follow up with the researcher and did not make a prompt written evaluation of the reports received. FDA review of long-term study results did not include a reexamination of animal tissue slides which, along with notes from the physical examination of the animal, are the basis for pathology diagnoses used to assess the cancer-causing potential of a substance. Because the contract for this study did not specify the types of data FDA would need to evaluate study results, some data were submitted late or not recorded. FDA does not have guidelines for design data recording and reporting, and statistical evaluation for long-term toxicity studies such as this one. Statistical procedures used in evaluating test data were criticized by reviewers. Many deviations from acceptable laboratory procedures were revealed in a FDA inspection of the nitrite researcher's laboratory.
Recommendation for Executive Action
Comments: Please call 202/512-6100 for additional information.
Recommendation: The Secretary of Health, Education, and Welfare should direct the FDA Commissioner to: establish guidelines on when site visits are appropriate during long-term toxicity studies; develop a system for ensuring the accuracy of pathological diagnoses for FDA-sponsored studies on which regulatory action is contemplated and consider the need for verifying tissue slide diagnoses as part of that process; and develop guidelines for design and data collection and reporting of long-term toxicity studies and establish standards and methods for statistically evaluating such studies.