The Importance of Ranking Possible Carcinogenic Hazards Using HERP 1

Testing chemicals 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. It is better to admit this than to provide the public with worst-case scenarios or to pretend that QRA is scientifically justifiable. The HEW index uses the same animal results and similar statistical methods as the usual low-dose linear estimation of risk; however, our purpose is to compare possible carcino- genic hazards from a variety of naturally occuring and synthetic chemicals, not to perform risk assessments. Our ranking is based on a simple measure that indicates what percentage of a standardized rodent tumorigenic dose a human gets from a given exposure. Recently, we have discussed advances in understanding the role of cell proliferation in the mechanisms of carcinogenesis, which suggest that estimates of risk to humans from low doses of rodent carcinogens have been markedly overesti- mated. The high doses administered in animal cancer tests are postulated to induce chronic cell proliferation, which itself is mutagenic in several ways.('J) Since cell prolifcration due to toxicity is not observed at low doses, the cancer risk at low doses is likely to be much lower than previously thought, particularly for nongenotoxic compounds. As more theory is developed and more evi- dence is produced about the mechanisms of carcinogen- esis, the ranking of hazards by the simple HERP index can be improved (as can risk assessment) by taking into account information on a given chemical about mecha- nism, shape of the dose response, and mutagenicity.