A brief review of modern toxicologic pathology in regulatory and explanatory toxicity studies of chemicals

Abstract

Macroscopic and histologic evaluation of animal studies for general toxicity and carcinogenicity are cornerstones of the risk assessment of new chemical entities. Standard toxicopathologic evaluation is mainly based on the study of paraffin sections stained with hematoxylin and eosin. There are, however, a number of new approaches and techniques which have improved the objectivity of evaluation and the accuracy of cell identification, and provided deeper insight into the molecular biological mechanisms of toxicity and carcinogenicity. Such approaches include the standardization of the nomenclature, the creation of data banks for morphological alterations, the use of computers to register pathological findings in toxicity studies and to statistically evaluate incidences, and the use of morphometry. Other modern techniques are immunohistochemistry, in situ hybridization, and the assessment of cell kinetics.

Toxicologic Pathology in the 21st Century

“…The use of biomarkers, measured with different methods, is well established in toxicology and toxicologic pathology. Examples include In life observations such as safety pharmacology parameters, clinical chemistry parameters, or increasingly used imaging methods (Ying and Monticello 2006; Xie et al 2012) Macroscopic and organ weight data (Cohen 2010) Histopathological findings such as aberrant colon crypts, peroxisome proliferation, chronic irritation, or basophilic liver foci (Ettlin et al 2010a, 2010b) Molecular investigations including immunohistochemistry, in situ hybridization, or flow cytometry (Ettlin et al 1991; Gillett and Chan 1999) In vivo and in vitro genotoxicity testing (Mahadevan et al 2011) Biomarkers have many advantages and may be used as surrogate markers for the ultimate effect of interest (Collings and Vaidya 2008). They need to be validated for their relevance and reliability for early detection of toxic effects.…”

“…Molecular investigations including immunohistochemistry, in situ hybridization, or flow cytometry (Ettlin et al 1991; Gillett and Chan 1999)…”