Pathology Requirements for Two-year Rodent Studies II. Alternative Approaches

Abstract

The preceeding paper described the origin and evolution of the pathology portion of carcinogen bioassays conducted under the direction of the National Cancer Institute (NCi) and subsequently by the National Toxicology Program (NTP). Review of 277 studies conducted under the NCI/NTP protocol suggested that the present number of tissues/organ5 was in excess to what is needed to detect if a given chemical induces cancer in rats and/or mice. In addition, the ability of the previous protocol to detect and define non-neoplastic chemically related lesions may be inadequate. This paper describes alternative pathology protocols and proposes one that will answer the question of a given chemicals' carcinogenic potential while at the same time give superior information on nonneoplastic chemical related pathology. In addition this protocol will reduce the volume of histopathology required in most studies by over 50%.

Pathobiology of Aging Mice and GEM

“…38,192 However, comprehensive pathology protocols that evaluate 40 or more tissues on 10 to 20 slides rapidly become a major expense. Abbreviated protocols that emphasize confirmed or expected target tissues have been explored as cost-saving alternatives 152 and may be statistically justifiable in certain situations. At a minimum, * References 42, 131, 176, 192, 211, 225, 235.…”

Pathology and Tissue Sampling Protocols for Rodent Carcinogenicity Studies: Time for Revision

“…In the field of pharmaceuticals, the International Conference on Harmonization (ICH) has made great strides in harmonizing the guidelines for carcinogenicity testing between the United States, Japan, and the European Union (25) (21,22).…”

The 26-Week Tg.Rash2 Mice Carcinogenicity Studies

“…The value of examining the full tissue list in lower dose groups has been discussed before for 2-year rodent and nonrodent studies, and alternative tissue lists have been proposed for 2-year rodent studies (McConnell 1983; Weddle, Mahrt, and Schmidt 2012). However, the very high incidence of spontaneous tumors in 2-year rodent models can certainly pose problems in developing and adopting a select tissue list with lesser number of tissues than that for control and high-dose groups.…”

“…This tissue list is the same as the one used by the International Life Science Institute Health and Environmental Science Institute’s (ILSI HESI) research program to characterize the transgenic mouse models for carcinogenicity assessment (Robinson and MacDonald 2001). With minor variations, this full tissue list is similar to the ones recommended by the National Toxicology Program and the Society of Toxicologic Pathology and is commonly used in the U.S. and EU carcinogenicity studies (McConnell 1983; Bregman et al 2003; Hayes et al 2011). The value of examining this full tissue list in lower dose groups has been discussed before for 2-year rodent studies (McConnell 1983) and for nonrodent toxicity studies (Weddle, Mahrt, and Schmidt 2012).…”

“…With minor variations, this full tissue list is similar to the ones recommended by the National Toxicology Program and the Society of Toxicologic Pathology and is commonly used in the U.S. and EU carcinogenicity studies (McConnell 1983; Bregman et al 2003; Hayes et al 2011). The value of examining this full tissue list in lower dose groups has been discussed before for 2-year rodent studies (McConnell 1983) and for nonrodent toxicity studies (Weddle, Mahrt, and Schmidt 2012). Based on the retrospective analysis of our extensive database of Tg.rasH2 mouse studies conducted at our facility, we propose that a full tissue list be examined as usual in the control and high-dose groups but only select tissues be examined in low- and mid-dose groups.…”