SPONTANEOUS NEOPLASM INCIDENCES IN FISCHER-344 RATS AND B6C3F(1) MICEIN 2-YEAR CARCINOGENICITY STUDIES - A NATIONAL-TOXICOLOGY-PROGRAM UPDATE

Spontaneous neoplasm rates were determined for control Fischer 344 (F3 44) rats and B6C3F(1) mice from 2-yr rodent carcinogenicity studies ca rried out by the National Toxicology Program (NTP). The most frequentl y occurring neoplasms in untreated male F344 rats were testicular aden oma (89.1%), mononuclear cell leukemia (50.5%), adrenal gland pheochro mocytoma (31.9%), and pituitary gland neoplasms (30.4%). For untreated female F344 rats, the most frequently occurring neoplasms were pituit ary gland neoplasms (54.2%); mammary gland fibroadenoma (41.2%), and m ononuclear cell leukemia (28.1%). The: most frequently occurring neopl asms in untreated male B6C3F, mice were liver adenoma/carcinoma (42.2% ), lung adenoma/carcinoma (20.5%), and malignant lymphoma (8.3%). For untreated female B6C3F, mice, the most frequently occurring neoplasms were liver adenoma/carcinoma (23.6%), malignant lymphoma (20.9%), and pituitary gland adenoma/carcinoma (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 tum ors 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 sho wed the opposite trend (60.7% vs 30.4%). The most likely explanation f or this difference is related to the individual housing of chamber con trols and the group housing of feeding study controls. Differences in diagnostic criteria may influence reported tumor rates. To ensure cons istency and comparability of tumor diagnosis from study to study, the NTP uses rigorous histopathology quality assurance and peer review pro cedures. Biological factors such as body weight may also affect tumor incidence. For example, increased body weights are associated with inc reased incidences of certain site-specific neoplasms, especially pitui tary gland and mammary gland neoplasms in rats and liver tumors in mic e. The presence of Helicobacter hepaticus has been associated with an increased incidence of liver neoplasms in male B6C3F, mice. Other fact ors that may produce differences in control tumor rates from study to study include diet, environmental factors, genetic drift, study durati on, and survival differences. The NTP database provides historical con trol data that may be useful in 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.