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Four widely used in vitro assays for genetic toxicity were evaluated for their ability to predict the carcinogenicity of selected chemicals in rodents. These assays were mutagenesis in Salmonella and mouse lymphoma cells and chromosome aberrations and sister chromatid exchanges in Chinese hamster ovary cells. Seventy-three chemicals recently tested in 2-year carcinogenicity studies conducted by the National Cancer Institute and the National Toxicology Program were used in this evaluation. Test results from the four in vitro assays did not show significant differences in individual concordance with the rodent carcinogenicity results; the concordance of each assay was approximately 60 percent. Within the limits of this study there was no evidence of complementarity among the four assays, and no battery of tests constructed from these assays improved substantially on the overall performance of the Salmonella assay. The in vitro assays which represented a range of three cell types and four end points did show substantial agreement among themselves, indicating that chemicals positive in one in vitro assay tended to be positive in the other in vitro assays.

ABSTRAC~Spontaneous neoplasm rates were determined for control Fischer 344 (F344) rats and B6C3Fl mice from 2-yr rodent carcinogenicity studies carried out by the National Toxicology Program (NTP). The most frequently occurring neoplasms in untreated male F344 rats were testicular adenoma (89. I 56). mononuclear cell leukemia (50.5%), adrenal gland pheochromocytoma (3 1.9%). and pituitary gland neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring neoplasms were pituitary gland neoplasms (54.2%). mammary gland fibrondenoma (41.2%). and mononuclear cell leukemia (28.1 8). The most frequently occurring neoplasms in untreated male B6C3Fl mice were liver adenomdcarcinoma (42.2%). lung adenomdcarcinoma (20.5%), and malignant lymphoma (8.3%). For untreated female B6C3F, mice, the most frequently occurring neoplasms were liver adcnomdcarcinomn (23.68). malignant lymphoma (20.9%). and pituitary gland adenomdcarcinoma (14.8%). The tumor rates observed in feeding study (untreated) and inhalation study (chamber) control rats were generally similar. The major exceptions were pituitary gland tumors and testicular adenoma in male F344 rats. The overall incidence of testicular adenoma was much lower in chamber controls (69.4%) than in feeding study controls (89.1%). whereas pituitary gland neoplasms showed the opposite trend (60.7% vs 30.4%). The most likely explanation for this difference is related to the individual housing of chamber controls and the group housing of feeding study controls. Differences in diagnostic criteria may influence reported tumor rates. To ensure consistency and comparability of tumor diagnosis from study to study, the NTP uses rigorous histopathology quality assurance and peer review procedures. Biological factors such as body weight may also affect tumor incidence. For example, increased body weights are associated with increased incidences of certain site-specific neoplasms, espccially pituitary gland and mammary gland neoplasms in rats and liver tumors in mice. The presence of Helicobacter hepporicrrs has been associated with an increased incidence of liver neoplasms in male B6C3FI mice. Other factors that may produce differences in control tumor rates from study to study include diet, environmental factors. genetic drift. study duration. and survival differences. The NTP database provides historical control data that may b e useful j n the evaluation of possible chemically related changes in tumor incidence. However, it is essential that the study being evaluated be comparable to those in the NTP database with respect to those factors that are known to influence tumor occurrence.

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