Causes of Death in Rodent Toxicity and Carcinogenicity Studies

Ettlin, Robert A.; Stirnimann, Peter; Prentice, David E.

doi:10.1177/019262339402200210

Cited by 38 publications

(30 citation statements)

References 13 publications

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“…Although the fatal neoplastic lesions were distributed in this study as described in previous reports of carcinogenicity studies using Sprague-Dawley derived rats [2,6], the incidence of fatal neoplasms was relatively low in this study, probably because there were more cases of chronic progressive nephropathy causing earlier death. The tumor incidences in males and females of both groups in this study were comparable with those reported by Muraoka et al [10], but much higher than in Prejean et al [12] who reported incidences of 34% and 58% in males and females, respectively.…”

Section: Discussionmentioning

confidence: 44%

Spontaneous Neoplastic Lesions in Aged Sprague-Dawley Rats.

et al. 2001

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Neoplastic lesions were observed in untreated aged Sprague Dawley (SD) rats throughout their lifespan starting at 5 weeks. Their mean survival times were 89 to 105 weeks of age. The total tumor incidences were 70 to 76.7% and 87 to 95.8% in males and females, respectively. The common neoplasmas were pituitary adenoma and adrenal pheochromocytoma in both sexes, testicular Leydig cell tumor in males and mammary gland tumors, thyroidal C-cell adenoma and uterine stromal polyp in females.

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Section: Discussionmentioning

confidence: 44%

Spontaneous Neoplastic Lesions in Aged Sprague-Dawley Rats.

et al. 2001

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“…The 3 most common contributing causes of death in F344 rats are leukemia, pituitary gland tumors, and (for male rats) nephropathy (5,6). Rats fed the NTP-2000 had slightly decreased incidences of leukemia (feeding studies only), significantly decreased incidences of pituitary gland tumors, and perhaps most importantly, striking decreases in the incidence and severity of nephropathy (especially for males).…”

Section: Tumor Incidence Datamentioning

confidence: 99%

Effect of Diet and Animal Care/Housing Protocols on Body Weight, Survival, Tumor Incidences, and Nephropathy Severity of F344 Rats in Chronic Studies

et al. 2003

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Diet is an important environmental factor affecting body weight, survival, and age-related diseases of rodents. The NIH-07 open formula diet was the diet used in the National Toxicology Program's (NTPs) rodent carcinogenicity studies from 1980 to 1994. In 1994 the NTP began using a new diet designated the NTP-2000 diet. This paper compares body weight, survival, tumor incidence, and nephropathy severity in untreated control groups of Fischer 344 (F344) rats fed the NTP-2000 or NIH-07 diets, using data from 22 separate 2-year feed and inhalation studies. The feed studies were conducted in 3 different facilities, and all the inhalation studies were conducted in a single facility. During feed studies, rats were group housed in polycarbonate cages and fed diets in powder (mash) form, while in inhalation studies, rats were housed individually in wire mesh cages, and fed diets in pelleted form. Survival was significantly ( p < 0.05) higher in groups fed NTP-2000 diet compared to the corresponding groups fed NIH-07 diet, irrespective of sex or housing conditions. Use of the NTP-2000 diet was also associated with a decreased incidence of pituitary gland tumors in both sexes and decreased incidences of adrenal pheochromocytoma and preputial gland tumors in males. The incidence and severity of nephropathy was also decreased in animals receiving the NTP-2000 diet, especially males. The decreased nephropathy severity and the decreased incidence of pituitary gland tumors are likely the major factors contributing to the improved survival of rats receiving the NTP-2000 diet relative to those given the NIH-07 diet. These data also support earlier findings that decreased incidences of adrenal pheochromocytoma are associated with reduced nephropathy severity in male F344 rats. Throughout the two-year study female rats receiving the NTP-2000 diet were significantly ( p < 0.05) lighter than those receiving the NIH-07 diet. However, it is uncertain if this difference can be attributed to the NTP-2000 diet, since implementation of this diet by the NTP approximately coincided with changes in the F344 rat production colony that resulted in somewhat lighter animals being provided to the NTP. Controls from inhalation studies and feed studies differed significantly ( p < 0.01) in the incidence of a variety of tumors, irrespective of diet. This suggests that differences in animal care and housing protocols may impact tumor incidence in F344 rats, most notably pituitary gland and testis tumors.

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“…Factors influencing spontaneous tumor incidence are reviewed by several authors (Everett, 1984;Hardisty, 1985;Gopinath, 1994). However, most of this is lifetime data (Maita et al, 1988;Ettlin et al, 1994); therefore it was considered useful to obtain data on tumor occurrence in animals dying during their first year of life, since tumors observed in treated animals prior to completion of a study may pose problems in interpretation. This report is intended to establish a general profile of tumor occurrence in CD-1 mice and SD rats during the first 50 weeks of chronic toxicity/carcinogenicity studies.…”

Section: Introductionmentioning

confidence: 99%

Early Occurrence of Spontaneous Tumors in CD-1 Mice and Sprague—Dawley Rats

Son¹,

Gopinath²

2004

Toxicol Pathol

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It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young control CD-1 mice and Sprague-Dawley rats. Data from 20 rat and 20 mouse carcinogenicity studies conducted between 1990 and 2002 at Huntingdon Life Sciences, UK, were collected and evaluated. The route of administration was either dietary or oral gavage, and the analysis was confined to sporadic deaths (decedents) in control groups occurring during the first 50 weeks of study. In addition, tumor occurrence between 50-80 weeks were compared. In mice, the most common tumor was lymphoma, followed by bronchiolo-alveolar adenoma. In rats, the most common tumor was adenoma of the pituitary gland, followed by mammary fibroadenoma, and adenocarcinoma. When studies of up to 50 weeks, between 50 and 80 weeks, and at 2-year termination were compared, there was no great difference in tumor occurrence except in male rats, in which the most common tumor up to 50 weeks on study was lymphoma, whereas the most common tumor between 50-80 weeks and at 2 years was pituitary adenoma.

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Causes of Death in Rodent Toxicity and Carcinogenicity Studies

Cited by 38 publications

References 13 publications

Spontaneous Neoplastic Lesions in Aged Sprague-Dawley Rats.

Spontaneous Neoplastic Lesions in Aged Sprague-Dawley Rats.

Effect of Diet and Animal Care/Housing Protocols on Body Weight, Survival, Tumor Incidences, and Nephropathy Severity of F344 Rats in Chronic Studies

Early Occurrence of Spontaneous Tumors in CD-1 Mice and Sprague—Dawley Rats

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