Tumor site concordance and genetic toxicology test correlations in NTP 2-year gavage, drinking water, dermal, and intraperitoneal injection studies

Abstract

The National Toxicology Program has conducted 594, 2-year studies exposing various strains of rats and mice via different routes of exposure. In the current study, we analyze the results from 108 chemicals tested in 106, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via gavage. An additional 18, 2-year gavage studies have been conducted in Osborne–Mendel rats and B6C3F1 mice on 19 different chemicals. We analyze the results from 23 chemicals tested in 21, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via drinking water; 18 chemicals tested in 18, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via dermal application; and 11 chemicals tested in 11, 2-year studies conducted by exposing F334/N rats and B6C3F1 mice via intraperitoneal injection. The results from these 174 studies are analyzed and discussed separately. The neoplasticity of each chemical was analyzed for tumor incidence by species–sex category, tumor site concordance across species, and tumor site concordance across sex within species. When available the Ames Salmonella mutagenicity assay results, and any results from a test for genotoxicity other than the Ames test, were correlated with the neoplasticity results. Tumor site concordance across sex within species is generally higher than tumor site concordance across species. In addition, the high degree of variability of Ames test results suggests that historical Ames test data are less reliable than recent results conducted under good laboratory practices and employing Organization for Economic Cooperation and Development protocols relevant to the physicochemical characteristics of the test chemical.