Effects of Treatment-Induced Mortality and Tumor-Induced Mortality on Tests for Carcinogenicity in Small Samples

Bailer, A. John; Portier, Christopher J.

doi:10.2307/2531856

Cited by 280 publications

(303 citation statements)

References 11 publications

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“…Tests of pairwise comparisons of the neoplastic and non-neoplastic lesions for each exposed group with the controls was conducted using the Poly-k test (24,29,30). A kvalue of 3 was used in these analyses (30).…”

Section: Resultsmentioning

confidence: 99%

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Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

Howard

Eppley

Stack

et al. 2001

Environ Health Perspect

131

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Fumonisin B1 (FB1) is a mycotoxin isolated from Fusarium fungi that contaminate crops worldwide. A previous study demonstrated that FB1 promoted preneoplastic foci in initiated rats and induced hepatocellular carcinomas in BD IX rats at 50 parts per million (ppm), but fundamental dose-response data were not available to assist in setting regulatory guidelines for this mycotoxin. To provide this information, female and male F344/N/Nctr BR rats and B6C3F1 Nctr BR mice were fed for two years a powdered NIH-31 diet containing the following concentrations of FB1: female rats, 0, 5, 15, 50, and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not tumorigenic in female F344 rats with doses as high as 100 ppm. Including FB1 in the diets of male rats induced renal tubule adenomas and carcinomas in 0/48, 0/40, 9/48, and 15/48 rats at 0, 5, 15, 50, and 150 ppm, respectively. Including up to 150 ppm FB1 in the diet of male mice did not affect tumor incidence. Hepatocellular adenomas and carcinomas were induced by FB1 in the female mice, occurring in 5/47, 3/48, 1/48, 19/47, and 39/45 female mice that consumed diets containing 0, 5, 15, 50, and 80 ppm FB1, respectively. This study demonstrates that FB1 is a rodent carcinogen that induces renal tubule tumors in male F344 rats and hepatic tumors in female B6C3F1 mice.

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Section: Resultsmentioning

confidence: 99%

“…A kvalue of 3 was used in these analyses (30). The analysis includes a risk-weight adjustment on animals that died before completion of the study and reports an adjusted rate of lesion incidence.…”

Section: Resultsmentioning

confidence: 99%

Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

Howard

Eppley

Stack

et al. 2001

Environ Health Perspect

131

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show abstract

“…differential mortality). Bailer and Portier (1988) addressed the survival issue by defining a modified sample size , where δ cij is a weight for animal j in group i. Clearly an animal that developed a tumor was at risk of tumor onset and thus receives a weight of 1.…”

Section: Introductionmentioning

confidence: 99%

Incorporating Historical Control Data When Comparing Tumor Incidence Rates

Peddada

Dinse

Kissling

2007

Journal of the American Statistical Association

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Animal carcinogenicity studies, such as those conducted by the U.S. National Toxicology Program (NTP), focus on detecting trends in tumor rates across dose groups. Over time, the NTP has compiled vast amounts of data on tumors in control animals. Currently, this information is used informally, without the benefit of statistical tests for carcinogenicity that directly incorporate historical data on control animals. This article proposes a survival-adjusted test for detecting doserelated trends in tumor incidence rates, which incorporates data on historical control rates and formally accounts for variation in these rates among studies. An extensive simulation, based on a wide range of realistic situations, demonstrates that the proposed test performs well in comparison to the current NTP test, which does not incorporate historical control data. In particular, our test can aid in interpreting the occurrence of a few tumors in treated animals that are rarely seen in controls. One such example, which motivates our work, concerns the analysis of histiocytic sarcoma in the NTP's 2-year cancer bioassay of benzophenone. Whereas the occurrence of three histiocytic sarcomas in female rats was not significant according to the current NTP testing procedure (P = 0.074), it was highly significant (P = 0.004) when control data from six recent historical studies were included and our test was applied to the combined data.

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“…The tumor data were analyzed for dose response relationship and pairwise comparisons of vehicle control group with each of the treated groups were performed using the Poly-k method described in the paper of Bailer and Portier (1988) and Bieler and Williams (1993). One critical point for Poly-k test is the choice of the appropriate value of k. For long term 104 week standard rat and mouse studies, a value of k=3 is suggested in the literature.…”

Section: Tumor Data Analysismentioning

confidence: 99%

Sodium-Glucose Cotransporter 2 Inhibitors: The New Option for Diabetes Mellitus Management

Powell¹,

Miller²,

Taylor³

2015

Southern Medical Journal

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Effects of Treatment-Induced Mortality and Tumor-Induced Mortality on Tests for Carcinogenicity in Small Samples

Cited by 280 publications

References 11 publications

Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

Incorporating Historical Control Data When Comparing Tumor Incidence Rates

Sodium-Glucose Cotransporter 2 Inhibitors: The New Option for Diabetes Mellitus Management

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