Best Practices Guideline: Toxicologic Histopathology

Crissman, James W.; Goodman, Dawn G.; Hildebrandt, Paul K.; Maronpot, Robert R.; Prater, Donald; Riley, Julia H.; Seaman, William; Thake, Daryl C.

doi:10.1080/01926230490268756

Cited by 322 publications

(286 citation statements)

References 15 publications

(11 reference statements)

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“…The histopathologic reading was performed by two board-certified veterinary histopathologists (J.W., F.S.) in a blinded manner according to the best practice guidelines of the Society of Toxicologic Pathology (20). In general, structure and classification of the histopathology evaluation followed the logical framework described elsewhere (21,22).…”

Section: Macroscopic Skin Findings and Histologymentioning

confidence: 99%

Gadolinium‐based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Sieber

Lengsfeld

Walter

et al. 2008

Magnetic Resonance Imaging

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Purpose:To investigate the role of excess ligand present in gadolinium (Gd) -based contrast agents in the development of nephrogenic systemic fibrosis (NSF). Using a dosing regimen to simulate the exposure seen in patients with severe renal impairment, we investigated the effect of excess ligand on Gd-deposition and the depletion of endogenous ions. Materials and Methods:Gadodiamide and gadoversetamide were formulated with 0%, 5%, and 10% excess ligand. Forty-two, healthy, male Hannover Wistar rats received daily intravenous injections of each formulation over a period of 20 days. At the end of the study, histopathological analysis of the skin was performed and the concentrations of Gd, Zn, and Cu were measured in several tissues. The levels of Zn in the urine were also measured. Results:The most severe skin lesions were observed after injection of formulations containing 0% free ligand and in those animals with the highest Gd concentrations in the skin. There were no significant reductions in the levels of Zn or Cu observed in the skin; however, the levels of Zn in the urine were elevated following administration of formulations with the highest amount of excess ligand. Conclusion:Our findings suggest that there is an inverse correlation between the amount of excess ligand present in Gd-containing contrast agents and the amount of Gd in the tissue, and further underline the importance of the inherent stability of these agents in the development of NSF.

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Section: Macroscopic Skin Findings and Histologymentioning

confidence: 99%

Gadolinium‐based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Sieber

Lengsfeld

Walter

et al. 2008

Magnetic Resonance Imaging

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“…In other words, the study pathologist should be acquainted in advance with knowledge of the dose level and group assignment for each animal as well as other anatomic pathology data (macroscopic findings and organ weights) and, ideally, in-life data and summaries (e.g., clinical observations and clinical pathology data) which help in their assessment (Crissman et al 2004). The rationale for this recommendation is that foreknowledge substantially increases the sensitivity for detecting subtle lesions in neural tissues; this logic is no different from that used when designing the assessment for any other organ or system.…”

Section: Approach To Neuropathology Assessmentmentioning

confidence: 99%

STP Position Paper

Garman²,

et al. 2013

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The Society of Toxicologic Pathology charged a Nervous System Sampling Working Group with devising recommended practices to routinely screen the central nervous system (CNS) and peripheral nervous system (PNS) in Good Laboratory Practice-type nonclinical general toxicity studies. Brains should be weighed and trimmed similarly for all animals in a study. Certain structures should be sampled regularly: caudate/putamen, cerebellum, cerebral cortex, choroid plexus, eye (with optic nerve), hippocampus, hypothalamus, medulla oblongata, midbrain, nerve, olfactory bulb (rodents only), pons, spinal cord, and thalamus. Brain regions may be sampled bilaterally in rodents using 6 to 7 coronal sections, and unilaterally in nonrodents with 6 to 7 coronal hemisections. Spinal cord and nerves should be examined in transverse and longitudinal (or oblique) orientations. Most Working Group members considered immersion fixation in formalin (for CNS or PNS) or a solution containing acetic acid (for eye), paraffin embedding, and initial evaluation limited to hematoxylin and eosin (H&E)-stained sections to be acceptable for routine microscopic evaluation during general toxicity studies; other neurohistological methods may be undertaken if needed to better characterize H&E findings. Initial microscopic analyses should be qualitative and done with foreknowledge of treatments and doses (i.e., ''unblinded''). The pathology report should clearly communicate structures that were assessed and methodological details. Since neuropathologic assessment is only one aspect of general toxicity studies, institutions should retain flexibility in customizing their sampling, processing, analytical, and reporting procedures as long as major neural targets are evaluated systematically.

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“…Recently, a set of Best Practices for the conduct of histopathology review within nonclinical safety studies was endorsed by the STP (Crissman et al 2004). Key elements of these Best Practices indicate that the study pathologist should be informed as follows: (1) have knowledge of the treatment group from which the sample was obtained; and (2) have complete knowledge of all available study-related data that are associated with the animal from which the tissue was obtained.…”

mentioning

confidence: 99%

“…Research pathologists, and especially the Society of Toxicologic Pathology (STP), have closely examined regulatory study histopathology practices (Crissman et al 2004;Wandall, Hansson and Ruden 2007). Recently, a set of Best Practices for the conduct of histopathology review within nonclinical safety studies was endorsed by the STP (Crissman et al 2004).…”

mentioning

confidence: 99%

“…Although the final document will not be available until later, we wished to present our preliminary opinion based on the aforementioned Best Practices (Crissman et al 2004). The present authors recognize that histopathology is a special discipline in which considerations for best practices may differ from those of other disciplines used in biomarker evaluation.…”

mentioning

confidence: 99%

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