Growth, Body Weight, Survival, and Tumor Trends in F344/N Rats during an Eleven-Year Period

Abstract

Time trends for growth, body weight, survival and tumor prevalences in 144 diet control groups with a total of 5,184 male F344/N rats and 146 diet control groups with a total of 5,289 female rats ofNCI-NTP 2-yr chemical carcinogenicity studies started during an ll-yr period (1971 to 1981) in 11 toxicology testing laboratories were evaluated. Male and female rats in more recent studies grew faster and attained a higher body weight than rats from earlier studies. Survival of males showed a significantly decreasing trend over time, which may have been related to diseases associated with increasing body weight, prevalence ofleukemia and changes in criteria for euthanasia of moribund animals. The time trend for survival of females was not significant. There were highly significant(p < 0.001) positive time trends for prevalences ofleukemia, anterior pituitary tumors and thyroid C-cell tumors in both sexes, adrenal pheochromocytomas in males and mammary tumors and endometrial stromal polyps in females. The prevalence of mammary tumors in females and pituitary tumors in males had a highly significant (p < 0.01) positive association with body weight. Histological reevaluation of tumor prevalences in approximately 250 rats of each sex at each of 4 different time periods indicated that changes in diagnostic criteria may have contributed to but could not totally explain the increased prevalence ofleukemia. Changes in diagnostic criteria and the amount of tissue examined may have contributed to the increased prevalence of anterior pituitary tumors in both sexes and adrenal pheochromocytomas in males. Interlaboratory variability and changes in diet may also have contributed to the time-related trends.

RITA—Registry of Industrial Toxicology Animal data: The application of historical control data for Leydig cell tumors in rats

“…This is a well-known trend and has been described by many authors (e.g. Rao et al 1990). This trend is considered to be the main factor responsible for the reduction of LC adenoma incidences during the observation period in animals from breeders G and I.…”

Whodunnit?

“…But he did not mention some work that had already been done using isogenic strains. The problem in carcinogenicity screening tests of increasing tumour rates (in the anterior pituitary gland, for example) and decreasing survival, accompanied by an increase in body weight, was actually first reported in an isogenic strain, the F-344 rat 4 .…”

Historical Control Data of Organ Weight and Gross Findings in F344/DuCrj Rats and B6C3F<SUB>1</SUB> Mice

“…Although there are numerous reports on naturally occurring microscopic lesions [1,3,[5][6][7][8][9][10][11][12][13][14][15][16], there is a paucity of information on gross necro -psy findings in these strains of rodents . The purpose of this investigation was to establish a historical control data base of the organ weight and naturally occurring gross morphologic alterations which were observed in toxicological studies with F344 rats and B6C3F1 mice.…”