Tumor site concordance and genetic toxicology test correlations in NTP 2-year feed studies

Abstract

This study presents an analysis of species, sex concordance in tumorigenicity among National Toxicology Program (NTP) chemicals tested for carcinogenicity by feed. It includes mutagenicity and other genetic toxicology test results, as well as Log P values. A total of 213 chemicals were tested in 212 2-year studies by exposing F334/N rats and B6C3F1 mice in their feed. Twenty-two of the 213 chemicals tested were clearly neoplastic in male and female rats and mice. Thirteen of these 22 chemicals were positive in at least one Ames test representing a prediction accuracy of 59.1%. Seventy-six of 213 chemicals tested were not neoplastic in either rodent species. Of the 22 ubiquitously neoplastic chemicals, 14 were concordant for developing tumors at the same anatomical site both across species and across sex within species. Of the 22 ubiquitously neoplastic chemicals, none were concordant for developing tumors at the same anatomical site across species, but not across sex within species. The neoplastic response to chemicals administered in feed displays more concordance within either male or female rats, or male and female mice, than between male rats and male mice, or female rats and female mice. In the NTP feed studies, negative Ames test results are more predictive of neoplastic responses than positive Ames test results. Log P values for the chemicals that produced tumors in male and female rats and mice were compared to chemicals that did not produce tumors. A statistical comparison between these Log P values showed no relationship between Log P values and neoplasticity.