Proceedings of the 2015 National Toxicology Program Satellite Symposium

Elmore, Susan A.; Farman, Cindy; Hailey, James R.; Kovi, Ramesh C.; Malarkey, David E.; Morrison, James P.; Neel, Jennifer A.; Porter, Brian F.; Szabo, Kathleen A.; Teixeira, Leandro; Quist, Erin M.

doi:10.1177/0192623316631844

Cited by 6 publications

(16 citation statements)

References 104 publications

(137 reference statements)

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“…Within the Toxicologic Pathology community, the diagnostic approach for PCM across studies is currently not consistent (Keenan et Al. 2010;Elmore et Al. 2016), and similarly pathologists' approaches varied for this mock study #1.…”

Section: Resultsmentioning

confidence: 99%

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2)

et al. 2017

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Spontaneous rodent progressive cardiomyopathy (PCM) in the Sprague Dawley rat may confound identification and/or interpretation of potential test article (TA)-related cardiotoxicity. Pathologists apply diagnostic term(s) and thresholds for diagnosing and assigning severity grades for PCM and/or PCM-like (PCM/like) lesions consistently within a study, which is necessary to identify and interpret TA-related findings. Due to differences in training and/or experiences, diagnostic terms and thresholds may vary between pathologists. Harmonized terminology and thresholds across studies will generate better historical control data, will likely enhance interpretation of study data, and may further enhance our understanding of the spontaneous change. An assessment of the diagnostic approaches of a group of 37 pathologists identified an approach that is relatively easily applied; and if adopted, it could enhance diagnostic consistency across studies. This approach uses the single "slash" term "necrosis/inflammatory cell infiltrate (NICI)" as the diagnosis for the spectrum of lesions seen in younger rats, uses no threshold for diagnosis (e.g., diagnose all lesions clearly identifiable as PCM/like), and uses aggregate lesion size of approximately ≥45% of the field of view (FOV) using a 10×/22 eyepiece and the 40× objective or approximately ≥100% of the FOV using the 60× objective as the criterion separating minimal from mild severities.

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Section: Resultsmentioning

confidence: 99%

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2)

et al. 2017

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“…Additional characterization of tumors classified as MR and granular cell tumors and their potential histogenic similarity with MCT would also be valuable. Morphologic similarities between astrocytoma, MCT and MR have been repeatedly well described (Maekawa and Mitsumori, 1990;Nagatani et al, 2009;Weber et al, 2011;Boorman et al, 2012;Kaufmann et al, 2012;Elmore et al, 2016). It would be useful to determine if MR is a variant of MCT, which could be combined with MCT for statistical analysis purposes, or if they originate from a different subset of histiocytic cells.…”

Section: Distinguishing Between Astrocytomas and Microglial Cell Tumomentioning

confidence: 96%

“…The concept of MCT in rats has been gaining traction in the toxicologic pathology community. While microglial cell tumors were not a recognized entity until the work by Nagatani et al published in 2009, the proceeding of the 2011 and 2015 NTP satellite symposium's "Patholo-gy Potpourri" sessions report that the percentage of participating pathologists shown mystery slides of rat brain tumors before having seen the results of IHC staining supporting a microglial origin were 22% (2011) and 33% (2015) (Boorman et al, 2012;Elmore et al, 2016). The percentages were up to 65% (2011) after revealing the IHC results.…”

Section: Distinguishing Between Astrocytomas and Microglial Cell Tumomentioning

confidence: 99%

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

2019

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Rodent in vivo carcinogenicity bioassays are required for human risk assessment and have been utilized in this capacity for decades. Accordingly, there is an abundance of data that could be accessed and analyzed to better understand the translatability of xenobiotic-induced rodent tumors to human risk assessment. In the past decade, various groups have published assessments of the value garnered by these lifetime rodent studies. Results and recommendations from the International Council for Harmonization Expert Working Group (ICH-S1 EWG) on the predictability of the current testing paradigm and proposal for an integrated approach to human carcinogenicity risk assessment are pending. Central nervous system (CNS) tumors in rats are rare and translatability to human remains unknown. This review focuses on microglial cell tumors (MCT) of the CNS in rats including its classification, nomenclature, incidence and translatability to human risk assessment. Based on emerging immunohistochemistry (IHC) characterization, glial tumors previously thought of astrocytic origin are more likely MCTs. These may be considered rodent specific and glucose dysregulation may be one component contributing to their formation. Based on review of the literature, MCTs are rarely diagnosed in humans, thus this tumor type may be rat-specific. We propose to include MCTs as a tumor type in revised International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) classification and all glial tumors to be classified as MCTs unless proven otherwise by IHC.

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“…* Figures (3D–3I) “Proceedings of the 2015 National Toxicology Program Satellite Symposium: Elmore et al , 2016). Toxicol Pathol 45:1 ,11–51.…”

Section: Figurementioning

confidence: 99%

Metastasis to the F344 Rat Pancreas from Lung Cancer Induced by 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)- 1-butanol, Constituents of Tobacco Products

et al. 2018

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Lung cancer is the most common cause of cancer-related deaths in humans worldwide. There is strong evidence that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and its metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) play an important role in carcinogenesis caused by tobacco products. NNK and racemic NNAL are reported to induce lung and pancreatic tumors in rats. The carcinogenicity in Fischer 344 rats of NNK, NNAL, and its enantiomers ( R)-NNAL and ( S)-NNAL has been studied recently, and all test compounds induced significant numbers of lung tumors. We report here the detailed histopathological and immunohistochemical characterization of these tumors and their aggressive nature as shown by their metastasis locally and to the pancreas. The spectrum of treatment-related histopathological findings comprised pulmonary alveolar/bronchiolar (A/B) epithelial hyperplasia, A/B adenomas, and A/B carcinomas. A/B carcinomas frequently exhibited local invasion/metastasis within the mediastinum and thoracic cavity and distant metastasis to the pancreas that was confirmed by immunohistochemistry using the lung-specific markers prosurfactant protein-C and club (Clara) cell-10. Our observation regarding metastasis to the pancreas was an important, and unexpected, finding in this study both for the experimental animal model and potential human relevance.

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Proceedings of the 2015 National Toxicology Program Satellite Symposium

Cited by 6 publications

References 104 publications

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2)

A Diagnostic Approach for Rodent Progressive Cardiomyopathy and Like Lesions in Toxicology Studies up to 28 Days in the Sprague Dawley Rat (Part 1 of 2)

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

Metastasis to the F344 Rat Pancreas from Lung Cancer Induced by 4-(Methylnitrosamino)- 1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)- 1-butanol, Constituents of Tobacco Products

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