Activity profiles of carcinogenicity data: Application in hazard identification and risk assessment

Abstract

Animal cancer data play a primary role in human risk assessment due to the limited epidemiological data. The current database of test results from the NCI/NTP rodent bioassays provide valuable information concerning the carcinogenic potential of hundreds of environmental agents. An approach is presented to reduce and graphically display these data as activity profiles to allow visualization and assessment of tumor response trends across multiple parameters, e.g. species, sex, target site, and route of exposure. Spreadsheet graphics are used to construct the profiles organized on the multiple parameters of carcinogenicity in a format that enables comparative analysis among chemicals. Several example applications are described to illustrate the value of activity profiles in hazard identification and risk assessment. The NCI/NTP data used in developing this concept are from the Carcinogen Potency Database (CPDB) compiled by Gold et al. (Environ. Health Perspect. 103 (Suppl. 8) (1995) 3–122). Computer links to the underlying details in the CPDB are maintained such that specific histopathologies at individual tumor sites, duration of the study, dose–response data, and notes related to diet, survival, treatments, and the authors evaluation are available to aid in the assessment process. The profiles display carcinogen potency based on the tumorigenic dose rate 50 (TD 50), i.e. the chronic dose rate that would induce tumors in half of the test animals at the end of their standard lifespan adjusting for spontaneous tumors. The TD 50 values provide an index for establishing a relative potency ranking of the chemicals for any specific parameter, such as species or target site. An example ranking of hepatocarcinogens is presented to illustrate relative potencies for chemical analogs. The rank order indicates that the degree and type of halogenation of alkanes has a direct bearing on the carcinogenic potency of these compounds.