Spontaneous cardiomyopathy in young Sprague-Dawley rats: evaluation of biological and environmental variability.


:Cardiovascular safety signals in nonclinical studies remain among the main reasons for drug attrition during pharmaceutical research and development. Drug-induced changes can be functional and/or associated with morphological alterations in the normal heart histology. It is therefore crucial to understand the normal variations in histology to discriminate test article-related changes from background lesions. Rodent progressive cardiomyopathy is probably the most commonly encountered change in control animals of nonclinical toxicity studies. A multisite study mimicking standard short-term toxicity studies using young male Sprague-Dawley rats was performed to better characterize this finding. Using an enhanced sectioning method for this research study, it was observed that the incidence of background cardiomyopathy was 100%. The vast majority of the microscopic findings were inflammatory in nature, with associated necrotic changes (defined as necrosis/inflammatory cell infiltrate) and these changes were mainly located in the myocardium of the mid region of the ventricles (the left side being predominantly affected). The monitored environmental factors in this study (multiple facilities, study duration, handling) did not have an effect on the incidence or severity of the spontaneous cardiomyopathy. In addition, cardiac-specific serum troponin levels were measured and were within the published control range.


Toxicol Pathol


Toxicologic pathology


Chanut F,Kimbrough C,Hailey R,Berridge B,Hughes-Earle A,Davies R,Roland K,Stokes A,Casartelli A,York M,Jordan H,Crivellente F,Cristofori P,Thomas H,Klapwijk J,Adler R




Has Abstract


2013-01-01 00:00:00














  • Loss of Immunohistochemical Reactivity in Association With Handling-Induced Dark Neurons in Mouse Brains.

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    journal_title:Toxicologic pathology

    pub_type: 杂志文章


    authors: Soontornniyomkij V,Chang RC,Soontornniyomkij B,Schilling JM,Patel HH,Jeste DV

    更新日期:2020-04-01 00:00:00

  • Characterization of the promoting activity of thiobenzamide on liver carcinogenesis.

    abstract::To characterize the promoting activity of thiobenzamide (TB), a thiono-sulfur-containing xenobiotic, rats of both sexes were treated with the compound for 4 or 8 weeks after an initiating dose of diethyl-nitrosamine. The number, area (volume), and phenotypic complexity of the enzyme-altered hepatocyte foci were studie...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章


    authors: Malvaldi G,Chieli E,Saviozzi M

    更新日期:1986-01-01 00:00:00

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    abstract::In the context of human hematopathology, the terms myelodysplasia and Myelodysplastic Syndromes (MDS) are applied to disorders of hematopoiesis that are clonal, neoplastic, and, in most forms, manifested as ineffective hematopoiesis with characteristic morphologic abnormalities in multiple cell lines. Studies of human...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审


    authors: Blue JT

    更新日期:2003-01-01 00:00:00

  • Toxic effects of quinolone antibacterial agents on the musculoskeletal system in juvenile rats.

    abstract::Quinolone antibacterial agents have adverse effects on the musculoskeletal system in humans, consisting mainly of myalgia and arthralgia, and additionally of tendon disorders and rhabdomyolysis. The present study was conducted to examine the toxic effects of quinolones on the musculoskeletal system in juvenile rats us...

    journal_title:Toxicologic pathology

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    authors: Kashida Y,Kato M

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  • Statistical support of the proposed National Toxicology Program protocol.

    abstract::Statistical issues related to the design, analysis and interpretation of carcinogenicity studies are considered. A proposed modification of the "standard" National Cancer Institute (NCI) design of carcinogenicity studies in rodents is discussed. The primary objective was to obtain a design that maintained the power of...

    journal_title:Toxicologic pathology

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    authors: Haseman JK

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  • The future of preclinical animal models in pharmaceutical discovery and development: a need to bring in cerebro to the in vivo discussions.

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    journal_title:Toxicologic pathology

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    authors: Everitt JI

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    abstract::Pentostatin, an adenosine deaminase inhibitor, has been approved for the treatment of refractory hairy cell leukemia. In a preclinical toxicity study, Wistar rats were administered 0, 1, 10, 25, and 50 mg/kg (0, 6, 60, 150, and 300 mg/m2, respectively) pentostatin intravenously once a week for 26 wk (1.5-75-fold above...

    journal_title:Toxicologic pathology

    pub_type: 杂志文章


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    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审


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    authors: Levine GM,Brousseau P,O'Shaughnessy DJ,Losos GJ

    更新日期:1987-01-01 00:00:00

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    journal_title:Toxicologic pathology

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    authors: Nyska A,Haseman JK,Kohen R,Maronpot RR

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    pub_type: 杂志文章,评审


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    journal_title:Toxicologic pathology

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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章,评审


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    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审


    authors: Ewart-Toland A,Balmain A

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    journal_title:Toxicologic pathology

    pub_type: 杂志文章


    authors: Picut CA,Remick AK,de Rijk EP,Simons ML,Stump DG,Parker GA

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    journal_title:Toxicologic pathology

    pub_type: 杂志文章


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    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审


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    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审


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    journal_title:Toxicologic pathology

    pub_type: 杂志文章


    authors: Rahman N,Pervin M,Kuramochi M,Karim MR,Izawa T,Kuwamura M,Yamate J

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    journal_title:Toxicologic pathology

    pub_type: 杂志文章,评审


    authors: Johnson AN

    更新日期:1989-01-01 00:00:00