Natural and synthetic chemicals in the diet: A critical analysis of possible cancer hazards

Abstract

Current regulatory policy to reduce human cancer risks is based on the idea that chemicals which induce tumors in rodent cancer bioassays are potential human carcinogens. The chemicals selected for testing in rodents, however, are primarily synthetic. The enormous background of human exposures to natural chemicals has not been systematically examined. This has led to an imbalance in both data and perception about possible carcinogenic hazards to humans from chemical exposures. The regulatory process does not take into account: 1) that natural chemicals make up the vast bulk of chemicals to which humans are exposed; 2) that the toxicology of synthetic and natural toxins is not fundamentally different; 3) that about half of the chemicals tested, whether natural or synthetic, are carcinogens when tested using current experimental protocols; 4) that testing for carcinogenicity at near-toxic doses in rodents does not provide enough information to predict the excess number of human cancers that might occur at low-dose exposures; 5) that testing at the maximum tolerated dose (MTD) frequently can cause chronic cell killing and consequent cell replacement (a risk factor for cancer that can be limited to high doses), and that ignoring this effect in risk assessment can greatly exaggerate risks. This chapter examines critically the assumptions, methodology, results, and implications of regulatory cancer risk assessments of synthetic chemicals and compares synthetic chemicals to naturally-occurring chemicals in food. Our analyses are based on results in our Carcinogenic Potency Database (CPDB), which provide the necessary data to examine the published literature of chronic animal cancer tests; the CPDB includes results of 5620 experiments on 1372 chemicals. Specifically, the following are addressed: (1) Human exposure to synthetic chemicals compared to the broader and greater exposure to natural chemicals in the diet. (2) Cancer risk assessment methodology, including the use of animal data from highdose bioassays in which half the chemicals tested are carcinogenic. (3) Increased cell division as an important hypothesis for the high positivity rate in rodent bioassays, and the implications for risk assessment. (4) A broad perspective on possible cancer hazards from a variety of exposures to rodent carcinogens including natural dietary chemicals and synthetic chemicals, by ranking on the HERP index. HERP indicates what percentage of the rodent carcinogenic potency (TD50 in mg/kg/day) a human receives from an average daily lifetime exposure (mg/kg/day). We report 72 HERP values, ranging across 10 orders of magnitude. Results indicate that some historically high exposures in the workplace and some pharmaceuticals rank high in possible carcinogenic hazard, and that there is an enormous background of naturally-occurring rodent carcinogens in average consumption of common foods that casts doubt on the relative importance of low-dose exposures to residues of synthetic chemicals such as pesticides. (5) Identification and ranking of possible toxic hazards from exposures in the U.S. diet to naturally-occurring chemicals that have not been tested for carcinogenicity, using the HERT index. HERT is the ratio of Human Exposure/Rodent Toxicity in mg/kg/day expressed as a percentage, and rodent LD50 values are the measure of toxicity. This approach to prioritizing untested chemicals makes assessment of human exposure levels critical at the outset. We report 121 HERT values, ranging across 6 orders of magnitude.