Evaluating the credibility of histopathology data in environmental endocrine toxicity studies

Abstract

Agencies responsible for environmental protection are tasked with developing regulatory guidance that is based on the best available scientific evidence. Histopathology is a common endpoint in toxicologic bioassays; however, because of the subjective nature of this endpoint, and the advanced level of specialized training required for its effective utilization, the reliability of histopathology data can be inconsistent. Consequently, mechanisms for evaluating such data on a case-by-case basis are needed. The purposes of the present review are to describe a methodology that can be used to evaluate the credibility of histopathology findings and to discuss the results of such assessments as applied to real-world data collected from the scientific literature. A key outcome of these efforts was the finding that only 54% of the studies examined contained histopathology data that were considered to be either highly credible or credible, whereas data in 46% of those studies were of equivocal, dubious, or no credibility. In addition, the results indicated that the quality of the data examined tended to decline during the past 15 yr. The ultimate goals of the present review are to draw attention to reliability issues that can affect histopathology results, provide recommendations to improve the quality of this endpoint, and suggest an approach for the expeditious and judicious use of histopathology data in the weight-of-evidence determinations required for hazard and

Use of Severity Grades to Characterize Histopathologic Changes

“…Communication of grading criteria is also important when comparing critical findings of studies with the same compound in different test systems or species and across doses and exposure durations. Without suitably defined grading criteria for critical/key findings, reviewers may simply have to rely on a subjective understanding of grading descriptors, which may in some cases result in inconsistent and/or incorrect interpretations and lead to additional peer review by an independent pathology working group (PWG; Mann and Hardisty 2014; Wolf and Maack 2017; Wolf et al 2014).…”

Identification of genes required for eye development by high-throughput screening of mouse knockouts

“…Physiologic data were supported by histopathology, which continues to be the definitive assay in medicine for making most diagnoses 73,74 . For pipeline histopathologic evaluation, eyes were either enucleated or fixed in situ.…”

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

“…Similarly, funding agencies need to pay more attention to the intended use of histopathology in grant applications and insist on provision of appropriate expertise with an appropriate budget. Increased stringency surrounding the processes of funding and publishing studies might represent more effort for researchers, reviewers, and journal editors, but will reduce the instances of flawed histopathology we see in many journals today 73 .…”