Incidence of Spontaneous Central Nervous System Tumors in CD-1 Mice and Sprague-Dawley, Han-Wistar, and Wistar Rats Used in Carcinogenicity Studies

Abstract

The incidence and range of spontaneous central nervous system tumors were determined in control Charles River rodents (Sprague-Dawley, HanWistar, Wistar rats, and CD-1 mice) from regulatory carcinogenicity studies carried out over the period 2002 to 2013 and were compared with the previously published data. In both species, the brain was notably more affected than the spinal cord. Incidences were comparable overall between rat strains (2.33%, 2.54%, and 2.89% in Wistar, Sprague-Dawley, and Han-Wistar strains, respectively) and were low in CD-1 mice (0.42% in 104-week studies and 0.2% in 80-week studies). Predominant tumor types were granular cell tumors in Wistar and Han-Wistar rats and malignant astrocytoma in Sprague-Dawley rats. Male rats were more frequently affected than females, but no sex predilection was apparent in CD-1 mice. Occasional earlyonset tumors were diagnosed in rats from study week 23 onward. It is hoped that these results will provide the pathologist and the toxicologist with an up-to-date database of background neoplastic findings in widely used rodent strains.

Central nervous system tumors in 2-year rat carcinogenicity studies: perspectives on human risk assessment

“…Tumors of the CNS are rare in species commonly used in non-clinical safety testing, including rodent species used for long term assessment of carcinogenicity (Fraser, 1971;Solleveld et al, 1990;Weber et al, 2011;Kaufmann et al, 2012;Bertrand et al, 2014). In these species, CNS tumors are relatively more common in rats than mice, with incidences that vary according to gender, species, breeding lineages and era (Ward and Rice, 1982;Maekawa and Mitsumori, 1990;Bertrand et al, 2014). Time period-associated changes refer primarily to genetic drifting of bred rodents as well as the impact of a Society of Toxicologic Pathology (STP) position paper published in 2013, which recommended expanding the sectioning of the rodent brain from three to seven levels (Bolon et al, 2013).…”

“…A more extensive sampling of the brain is likely to increase the detection of small size tumors. Bertrand et al offer a relatively recent and robust break down of CNS tumor incidences by species, strain, gender and location (brain, spinal cord), with tumor types broken down into benign and malignant; and low or high grade (Bertrand et al, 2014).…”

“…If such data are available but do not support the final interpretation of the study, the data cannot be ignored and should be presented as part of the scientific discussion. If, however these preferred sources of historical data are not available, then published literature for same species and strain are most relevant and can be found in relatively recent publications (Krinke et al, 2000;Weber et al, 2011;Bertrand et al, 2014).…”

“…Until recently, astrocytoma has been the most com-mon CNS tumor diagnosed in Sprague Dawley rats, and by far the most common glial cell tumor in Sprague Dawley and Wistar Han rats (Bertrand et al, 2014). As previously mentioned, they are occasionally diagnosed as glioma, although recent literature clearly recommends differentiation based on cell type as defined by specific morphologic criteria (Weber et al, 2011;Kaufmann et al, 2012;Bertrand et al, 2014).…”

“…Until recently, astrocytoma has been the most com-mon CNS tumor diagnosed in Sprague Dawley rats, and by far the most common glial cell tumor in Sprague Dawley and Wistar Han rats (Bertrand et al, 2014). As previously mentioned, they are occasionally diagnosed as glioma, although recent literature clearly recommends differentiation based on cell type as defined by specific morphologic criteria (Weber et al, 2011;Kaufmann et al, 2012;Bertrand et al, 2014). Notably, spontaneous CNS tumors in rats classified as astrocytomas are invariably negative to glial fibrillary acidic protein (GFAP) staining, a well-established marker of astrocytes, although GFAP positive reactive (non-neoplastic) astrocytes are commonly observed in these tumors, particularly at the periphery and around blood vessels.…”