Early Onset of Spontaneous Renal Preneoplastic and Neoplastic Lesions in Young Conventional Rats in Toxicity Studies

Lanzoni, Anna; Piaia, Alessandro; Everitt, Jeffrey I.; Faustinelli, Ivo; Defazio, Rossella; Cavaliere, Luca; Cristofori, Patrizia

doi:10.1080/01926230701383202

Cited by 11 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In young adult rats (studies up to 26 weeks), the data on tumor incidences are limited. However, there are several case reports or organ-related summaries published (e.g., Chang et al 2008; Crabbs et al 2013; Matsushima et al 2010; Reindel et al 1996; Shiraki et al 2012; Tsunenari, Yamate, and Sakuma 1997), and summary data are available in the literature (e.g., Ikezaki, Takagi, and Tamura 2011; Lanzoni et al 2007; Son et al 2010). Tumors may be encountered in animals as young as 9 weeks.…”

Section: Discussionmentioning

confidence: 99%

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Weber¹

2017

Toxicol Pathol

View full text Add to dashboard Cite

A substantial quantity of data on Sprague-Dawley (SD) and Hannover Wistar rats strains have been published concerning their source, diet, and housing conditions, as well as the incidences of nonneoplastic lesions and neoplasms observed in different laboratories. Differences between the commonly used rat strains provided by different breeders (i.e., CD (SD) vs. Harlan Sprague-Dawley strain or Crl: WI(Han) vs. Wistar Hannover (Han)-derived strain, continued breeding by RCC Ltd., Switzerland, thereafter continued breeding by Harlan) may include, but are not limited to, body weight, incidence, and onset of major nonneoplastic lesions and neoplasms, and these can impact the development of a nonclinical safety program. Fisher 344 (F344) and SD rat strains generally have the highest tumor incidences, exceeding that in Wistar rats. Certain tumors are more commonly observed in one strain, and for some, the difference in incidence may be so significant that the tumor may even be considered characteristic for a specific strain (e.g., thymoma in Wistar and amphophilic renal adenoma in SD).

show abstract

Section: Discussionmentioning

confidence: 99%

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Weber¹

2017

Toxicol Pathol

View full text Add to dashboard Cite

show abstract

“…All macroscopic and microscopic findings (including a renal carcinoma in one mid dose female) were ruled incidental and unrelated to treatment. Renal tubular tumors have been observed sporadically in Sprague-Dawley rats of similar age [11] , [15] .…”

Section: Discussionmentioning

confidence: 99%

Safety studies conducted on pecan shell fiber, a food ingredient produced from ground pecan shells

Dolan¹,

Matulka²,

Worn³

et al. 2016

Toxicology Reports

View full text Add to dashboard Cite

Use of pecan shell fiber in human food is presently limited, but could increase pending demonstration of safety. In a 91-day rat study, pecan shell fiber was administered at dietary concentrations of 0 (control), 50 000, 100 000 or 150 000 ppm. There was no effect of the ingredient on body weight of males or females or food consumption of females. Statistically significant increases in food consumption were observed throughout the study in 100 000 and 150 000 ppm males, resulting in intermittent decreases in food efficiency (150 000 ppm males only) that were not biologically relevant. All animals survived and no adverse clinical signs or functional changes were attributable to the test material. There were no toxicologically relevant changes in hematology, clinical chemistry or urinalysis parameters or organ weights in rats ingesting pecan shell fiber. Any macroscopic or microscopic findings were incidental, of normal variation and/or of minimal magnitude for test substance association. Pecan shell fiber was non-mutagenic in a bacterial reverse mutation test and non-clastogenic in a mouse peripheral blood micronucleus test. Based on these results, pecan shell fiber has an oral subchronic (13-week) no observable adverse effect level (NOAEL) of 150 000 ppm in rats and is not genotoxic at the doses analyzed.

show abstract

“…In the case of AV tumors, very little information is available regarding their occurrence in SD rats. Lanzoni et al (2007) conducted a survey in young ( 18 weeks of age) SD rats from toxicity studies of shorter duration, reporting an overall incidence of 0.66% for preneoplastic and neoplastic lesions in the kidney; however, this study did not recognize AV tumors as a distinct entity and included foci of atypical hyperplasia. Females were affected more commonly than males (0.97% and 0.44%, respectively).…”

Section: Discussionmentioning

confidence: 99%

Occurrence of Spontaneous Amphophilic-Vacuolar Renal Tubule Tumors in Sprague-Dawley Rats from Subchronic Toxicity Studies

Crabbs

Frame

Laast³

et al. 2012

Toxicol Pathol

View full text Add to dashboard Cite

The low background incidence of tumors in rodents from subchronic toxicity studies makes it difficult to assess their relevance, especially when present only in treated animals. This report investigates the occurrence of renal tubule tumors (RTTs), specifically the amphophilic-vacuolar (AV) phenotypic variant, in young Sprague-Dawley (SD) rats from a survey of laboratories conducting subchronic toxicity studies spanning a period of 10 years (2002-2012). This survey establishes a general profile of tumor occurrence; it does not estimate overall incidence or prevalence. AV tumors are spontaneous, nontreatment-related tumors of familial origin, and morphologically distinct from conventional RTTs induced by exposure to renal carcinogens. They are composed of distinct lobules of large, round to polyhedral cells with vacuolated amphophilic to eosinophilic cytoplasm and prominent nucleoli. Data from five collaborating laboratories, representing 37 qualifying studies, are presented. In total, 58 renal tubule neoplasms were recorded in this data set. The AV tumor variant was reported more commonly than the conventional RTT (n = 45 and 13, respectively), and it was recorded in both experimental (n = 32) and control (n = 13) groups. AV tumors occurred more often in females (n = 34) than in males (n = 11); conventional RTTs were recorded more often in males (n = 9) than in females (n = 4). AV tumors often occurred in more than one rat within the same study (up to 7) and were documented to occur in rats as young as 7 to 10 weeks of age. Results from this survey indicate that AV tumors are being reported more commonly in recent years; the majority (n = 33) were reported in studies commencing since 2009. In conclusion, this study reaffirms that AV tumors are spontaneous, nontreatment-related lesions, and suggests that they may be more common than conventional RTTs in young SD rats. The authors propose that AV tumors be recorded separately from conventional RTTs in order to clearly distinguish these two renal tubule neoplasms from one another and allow for appropriate interpretation of a compound's potential carcinogenic effect in the kidney.

show abstract

Early Onset of Spontaneous Renal Preneoplastic and Neoplastic Lesions in Young Conventional Rats in Toxicity Studies

Cited by 11 publications

References 17 publications

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Differences in Types and Incidence of Neoplasms in Wistar Han and Sprague-Dawley Rats

Safety studies conducted on pecan shell fiber, a food ingredient produced from ground pecan shells

Occurrence of Spontaneous Amphophilic-Vacuolar Renal Tubule Tumors in Sprague-Dawley Rats from Subchronic Toxicity Studies

Contact Info

Product

Resources

About