Analysis of thresholds for carcinogenicity

Abstract

Re-evaluations of large prominent studies, e.g. the ED01 study and N-nitrosodiethylamine, unequivocally have demonstrated that thresholds exist for carcinogenicity when the dose–response curves for animal studies done at high doses are calculated according to fundamental principles of chemistry. This requires dose to be on a logarithmic scale and percent tumors on a linear scale. Fifteen compounds approved by the Flavor and Extract Manufacturers Association (FEMA) expert panel as Generally Recognized As Safe (GRAS) have been reported to be carcinogenic in rodent studies. The thresholds for tumors of these flavors were at least several orders of magnitude greater than the estimated daily dose of these flavoring agents to individuals in the United States. Similarly, comparisons of thresholds of carcinogenicity of chemicals and drugs to which humans are exposed with their exposure levels suggest that experimental animals are more sensitive to carcinogenicity than humans. The animal studies should be viewed as providing evidence for the safety of these flavors and other compounds at current levels of human exposure.