The importance of ranking possible carcinogenic hazards using HERP.

Content Provider	Semantic Scholar
Author	Gold, Lois Swirskey Bernstein, Leslie Ames, Bruce N.
Copyright Year	1990
Abstract	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 carcinogenic 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 overestimated. 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 evidence is produced about the mechanisms of carcinogenesis, 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 mechanism, shape of the dose response, and mutagenicity. About half of the chemicals tested for carcinogenicity in rats and mice are positive, and this proportion is similar for naturally occurring and synthetic chemi-
Starting Page	398
Ending Page	401
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://toxnet.nlm.nih.gov/cpdb/pdfs/RiskAnalysis1990.pdf
PubMed reference number	2287789v1
Volume Number	10
Issue Number	4
Journal	Risk analysis : an official publication of the Society for Risk Analysis
Language	English
Access Restriction	Open
Subject Keyword	Adverse reaction to drug Carcinogenesis Carcinogenicity Tests Carcinogens Cell Proliferation Estimated Evaluation procedure HEY2 wt Allele Malignant Neoplasms Rodent cancer risk
Content Type	Text
Resource Type	Article