A database of NTP short-term genetic toxicity test results and the results from carcinogenesis tests has been created. This database allows the evaluation of each short-term assay with respect to its ability to predict carcinogenesis or other short-term assay results. It also permits studies of the individual assays with respect to inter- and intra-laboratory reproducibility. Examination of test predictivity as a function of the potency of the short-term test (STT) and carcinogenicity test is continuing. The chemicals being evaluated comprise the 114-chemical dataset used previously to correlate qualitative STT results with carcinogenicity results. The short-term genetic toxicity results are being integrated with other toxicity and biochemical parameters of these chemicals in an attempt to improve the prediction of carcinogenicity and other toxic effects. A number of potency measures have been proposed for the Salmonella and carcinogenesis tests, but there are no commonly-accepted measures of potency for the other STTs, such as in vitro chromosome aberrations, in vitro SCE, or the mouse lymphoma test. The analyses of the potency measures for Salmonella are being redefined to fit the data from the mammalian cell assays, and will be used to evaluate the relationships of the in vivo tests with the carcinogenic potencies for the same chemicals. The database of Salmonella results was used to evaluate the ability of a number of procedures to predict mutagenicity. The predictivities for Salmonella mutagenicity of two computer-based structure- activity (SAR) systems, one empirical structure-activity system, and one physicochemical system, were determined for 100 chemicals. The chemical structures, or coded chemicals, were sent, without identifying them by name, to the participants. The study was designed to: measure the accuracy of the different test systems; identify the strengths and weaknesses of each system; and bring greater understanding to structure- activity predictions. The two computer-based SAR systems and empirical system gave equivalent predictivities (approx. 70-80%), while the physicochemical system was less effective (approx. 60%).

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021103-06
Application #
3841000
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code