Mega‐experiments to Identify and Assess Diffuse Carcinogenic Risks

Abstract

Diffuse carcinogenic risks, that is, those of low potency involving large areas of population and sometimes all mankind, pose a serious public health problem. Controlling these risks might help to reduce the incidence of, and mortality from, cancer. Because of their low expected carcinogenic potential, these risks are difficult to expose or assess. Epidemiologic investigation is of limited use in this field and yields its data too late to be useful. Experimental studies offer the only possible approach for assessing such risks. To increase experimental sensitivity and consistency of results, mega-experiments must be designed. That is, experiments that use a large number of animals with a well-known basic tumorigram, that extend the exposure and the biophase for as long as possible, that carefully observe the effects, and that are performed with suitable standardized methods. In the last 15 years the Ramazzini Foundation, in its Cancer Research Center at Bentivoglio, has conducted or planned five mega-experiments. Initial results indicate the great potential of these methods for identifying and assessing diffuse risks.

Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice

“…As already reported [Soffritti et al, 1999;Haseman et al, 2001;Huff et al, 2008;Soffritti et al, 2008], in longterm carcinogenicity bioassays the number of animals per sex/group and life span observation are critical points for identification and assessment of diffuse carcinogenic risks, defined as the exposure to a single or multiple agents or to mixtures that are expected to have limited carcinogenic potential because of the agent type (weak carcinogen) and/or dose/concentration (low), but that involve large group of the population (as is the case with APM). Concerning the prolonged (over 110 weeks of age) or lifespan duration of the experiment, we must consider that neoplastic response depends not only on the chemical-physical characteristics of the agent and its toxicological properties, the mode of exposure, and the type of animals, but also, to a greater extent, on the latency of the tumor which varies and may be very long.…”

Results of Long‐Term Carcinogenicity Bioassays on Coca‐Cola Administered to Sprague‐Dawley Rats

“…3,4 Long-term carcinogenicity bioassays on rodents, which reproduce exposure situations experienced by humans as much as possible, is in our opinion, a good approach to study the influence of dietary products on the incidence of spontaneous tumors in a controlled environment. 5,6 In an attempt to evaluate the interaction between one such product and tumor incidence in rodents, an experimental carcinogenicity bioassay was performed at the Cesare Maltoni Cancer Research Center (CMCRC) of the European Ramazzini Foundation (ERF). The product tested is a beverage mixture which is both caloric and widely consumed in most of the world-Coca-Cola.…”

First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats

“…For these reasons, and in light of the ever-increasing diffusion of APM in the diet of industrialized countries (particularly in products consumed by young children and pregnant women), we considered it important to perform a mega-experiment following today’s internationally recognized good laboratory practices for carcinogenicity bioassays and, more specifically, the life-span carcinogenicity bioassay design followed for many years at the CMCRC and described in previous publications (Soffritti et al 1999, 2002c). …”