Genetic activity profiles--application in assessing potential carcinogenicity of complex environmental mixtures

Abstract

Some knowledge of the potential genetic activity of a complex environmental mixture may be gained from an assessment of the genetic activity of its component chemicals. The expanded genetic activity profile (GAP) data-base provides a computer-generated graphic representation of genetic bioassay data as a function of dose of the substance tested. In addition, the atmospheric chemical compound (ACC) data-base contains information on chemical structures, properties, detection methods and sources of chemicals found in ambient air. Using the combined data-bases, information on the quantity of an individual chemical present within a mixture or fraction of a mixture may be related to the quantity (lowest effective dose; LED) of the chemical required to demonstrate a positive response in one or more genetic bioassays. Alternatively, quantitative information on the carcinogenic potency of each individual compound (TD50 value) may be related to the quantity present in the mixture or mixture fraction and used to calculate the percent human exposure dose/rodent potency dose (HERP) for the chemical. Using an additivity assumption, a conservative estimate of potential carcinogenic hazard for the mixture may be calculated based on the HERP indices for its chemical components. This conceptual approach is limited by the relatively small number of chemicals identified in complex mixtures for which genetic toxicology and animal cancer data exist.