Transition of Historical Control Data for High Incidence Tumors in F344 Rats

Kuroiwa, Yoshihiro; Andõ, Ryõ; Kasahara, Ken-ichiro; Nagatani, Mariko; Yamakawa, Seiki; Okazaki, Shuzo

doi:10.1293/tox.26.227

Cited by 13 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Even when considering endometrial proliferative lesions including precursor lesions of adenocarcinoma, acotiamide-HH-treated animals did not exhibit increased incidence of lesions. Numerous studies have reported the incidence of spontaneous neoplasms in F344 rats (Ando et al, 2008;Dinse et al, 2010;Haseman et al, 1998;Iwata et al, 1991;Kuroiwa et al, 2013;Maekawa et al, 1983;Maita et al, 1987;Takanobu et al, 2015). According to these studies, the incidence of EmA ranges from 0% to 22%.…”

Section: Discussionmentioning

confidence: 99%

Verification of a false positive in a two-year rat carcinogenicity study using dual control groups

et al. 2018

View full text Add to dashboard Cite

There is sometimes controversy over whether or not statistically significant responses produced in carcinogenicity studies have biologically significance. Ambiguous results from our previous two-year oral carcinogenicity study on acotiamide hydrochloride hydrate (acotiamide-HH), a prokinetic drug for functional dyspepsia, in rats made it unclear whether the drug may exhibit uterine carcinogenicity. To check this finding, we performed a second long-term carcinogenicity study using two identical control groups to more accurately evaluate uterine carcinogenesis by considering the incidence of spontaneous neoplasms. Female Fischer 344 rats were divided into three groups: the two control groups (control 1 and 2) were administered vehicle (0.5% w/v methylcellulose) and the acotiamide-HH-treated group was administered 2,000 mg/kg/day of acotiamide-HH by oral gavage for two years. Among all groups, the incidence of endometrial adenocarcinoma (EmA) was highest in the control 2 group, followed by the acotiamide-HH-treated group and the control 1 group. Moreover, acotiamide-HH did not affect the incidence of precursor lesions of EmA. In cases where an ambiguous difference is observed, the use of two control groups allows for a more informed interpretation of the findings in the drug-treated groups. The outcomes in this study strongly support the hypothesis that the increase in EmA in rats treated with acotiamide-HH in our previous study is unrelated to administration of the drug.

show abstract

Section: Discussionmentioning

confidence: 99%

Verification of a false positive in a two-year rat carcinogenicity study using dual control groups

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Lack of stability in controls may also reflect changes in study design-related parameters such as species/strain, eligibility criteria, route of administration, vehicle, reagents, chemical and equipment suppliers, feeding and housing practices, or may be the result of sampling error as when the measurements of interest have inherently high variance. Unexplained fluctuations in the frequency of spontaneous tumours in control rats have been reported in some research facilities (Ando et al, 2008;Kuroiwa et al, 2013). However, what little information is available suggests that, when laboratories are well managed, controls are repeatable.…”

Section: When Can Historical Controls Be Used?mentioning

confidence: 99%

Reducing sample size in experiments with animals: historical controls and related strategies

Kramer

Font

2015

Biol Rev

View full text Add to dashboard Cite

Reducing the number of animal subjects used in biomedical experiments is desirable for ethical and practical reasons. Previous reviews of the benefits of reducing sample sizes have focused on improving experimental designs and methods of statistical analysis, but reducing the size of control groups has been considered rarely. We discuss how the number of current control animals can be reduced, without loss of statistical power, by incorporating information from historical controls, i.e. subjects used as controls in similar previous experiments. Using example data from published reports, we describe how to incorporate information from historical controls under a range of assumptions that might be made in biomedical experiments. Assuming more similarities between historical and current controls yields higher savings and allows the use of smaller current control groups. We conducted simulations, based on typical designs and sample sizes, to quantify how different assumptions about historical controls affect the power of statistical tests. We show that, under our simulation conditions, the number of current control subjects can be reduced by more than half by including historical controls in the analyses. In other experimental scenarios, control groups may be unnecessary. Paying attention to both the function and to the statistical requirements of control groups would result in reducing the total number of animals used in experiments, saving time, effort and money, and bringing research with animals within ethically acceptable bounds.

show abstract

“…While the incidence of most tumour types shows little variability with time, remaining essentially unchanged over the past 20 years, a time-related drift in the incidence of some tumours such as pituitary and mammary tumours is well documented for some strains (e.g. Carlus et al, 2013;Kuroiwa et al, 2013;Ando et al, 2008;Baldrick, 2005;Brix et al, 2005;Tennekes et al, 2004;Keenan et al, 2002;Eiben and Bomhard, 1999;Haseman et al, 1998). In general, such genetic drift is more common with outbred Wistar and Sprague-Dawley rats.…”

Section: Impact Of the Paper Published In Plos One (Mesnage Et Al 2mentioning

confidence: 99%

“…Prejean et al, 1973;Durbin et al, 1966). The difference in the incidence of such lesions between strains, their contributing factors and their trends have been studied extensively and are well documented in the literature (e.g., Carlus et al, 2013;Kuroiwa et al, 2013;Ando et al, 2008;Baldrick, 2005;Brix et al, 2005;Tennekes et al, 2004;Keenan et al, 2002;Eiben and Bomhard, 1999;Haseman et al, 1998). The overall consensus is that different genetic predispositions underlie the development of these lesions for each strain.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Review of results published by Mesnage et al. (2015) in PLoS ONE and the laboratory findings communicated by Dr Samsel to Farm Wars

2015

EFSA Journal

View full text Add to dashboard Cite

In a paper published in PLoS One and entitled 'Laboratory rodent diets contain toxic levels of environmental contaminants: Implications for regulatory tests ', Mesnage et al. (2015) analysed commercial laboratory rodent diets for environmental contaminants and genetically modified organisms (GMOs). In samples from 13 different commercial rodent diets obtained from five continents, the authors of the study report the presence of pesticides, heavy metals, polychlorinated dibenzo-p-dioxins and dibenzofurans, and GMOs. The paper by Mesnage et al. (2015) provides a useful addition to the already existing knowledge in the field. However, there are several limitations with the methodological approach used by the authors, including insufficient information about the test material and methodology used, incomplete reporting of the data, and inappropriate interpretation of legislation and results. The vast majority of pesticides were absent (below the limit of detection), and where detected, the levels of pesticides, heavy metals and dioxins were only just above the limit of detection in the feed samples but below regulatory levels for feed and foodstuffs. Only in a limited number of feed diets did the authors report levels of lead that exceeded the maximum levels specified by legislation for foodstuffs. The application of the ADI concept to claim the existence of a health risk in rodents or to demonstrate background levels of diseases or disorders in rodents has no scientific justification. In an interview conducted with Dr Samsel, the farmwars.info website reports on the presence of glyphosate in three different rodent diets. The information reported on the website is not supported by sufficient detail or a reference to permit a full scientific review. In conclusion, no new scientific elements were provided that would impact on the validity of regulatory feeding tests in the EU.

show abstract

Transition of Historical Control Data for High Incidence Tumors in F344 Rats

Cited by 13 publications

References 10 publications

Verification of a false positive in a two-year rat carcinogenicity study using dual control groups

Verification of a false positive in a two-year rat carcinogenicity study using dual control groups

Reducing sample size in experiments with animals: historical controls and related strategies

Review of results published by Mesnage et al. (2015) in PLoS ONE and the laboratory findings communicated by Dr Samsel to Farm Wars

Contact Info

Product

Resources

About