ABSTRACT
Definitive epidemiological observations and investigations are the surest way to relate a specific etiologic agent-chemical, physical, or biological-causally with human neoplasms, but epidemiological studies are still relatively insensitive for identifying causative factors in human cancer. Such studies can only identify factors that are different between two populations and that are sufficiently important to play a determining role under the conditions of exposure. Furthermore, on the basis of epidemiological studies, it is extremely difficult to determine whether a specific chemical is or is not carcinogenic to the human because of the extended lag period between exposure and clinical occurrence of a neoplasm, the high background incidence of many cancers in the general population, the relatively imprecise knowledge of the nature of the exposure in most instances, and a number of other confounding variables. Only under exceptional circumstances such as the induction of rare and infrequent neoplasms-e.g., vinyl chloride and angiosarcoma (Dannaher et al., 1981)—is it possible to identify an agent as carcinogenic solely by epidemiological studies when the incidence of cancer induced by that agent is less than 50% more than the occurrence of the resulting cancer in the general human population. Therefore, a “negative” result of an epidemiological investigation must be considered as inconclusive for determining whether or not a relatively weak carcinogenic agent has a role in the etiology of human neoplasia. How, then, is it possible to identify actual and potential carcinogenic agents in our environment by methods other than epidemiological studies? This question has been answered in part by relating the results of additional studies, usually carried out with experimental animals, to the problem of the etiology of human cancer and the risks of environmental agents to populations and/or specific individuals. It is from such studies that government agencies make decisions that ultimately regulate the production and use of-and accordingly the exposures of populations to-agents determined to be actually or potentially carcinogenic for the human.
