Practical approaches for evaluating adrenal toxicity in nonclinical safety assessment

• Inomata Akira

  Tsukuba Drug Safety, Global Drug Safety, Biopharmaceutical Assessments Core Function Unit, Eisai Co., Ltd., 5-1-3 Tokodai, Tsukuba, Ibaraki 300-2635, Japan

• Sasano Hironobu

  Department of Pathology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan

Bibliographic Information

Other Title

• Concise Review : Practical approaches for evaluating adrenal toxicity in nonclinical safety assessment

Abstract

The adrenal gland has characteristic morphological and biochemical features that render it particularly susceptible to the actions of xenobiotics. As is the case with other endocrine organs, the adrenal gland is under the control of upstream organs (hypothalamic-pituitary system) in vivo, often making it difficult to elucidate the mode of toxicity of a test article. It is very important, especially for pharmaceuticals, to determine whether a test article-related change is caused by a direct effect or other associated factors. In addition, antemortem data, including clinical signs, body weight, food consumption and clinical pathology, and postmortem data, including gross pathology, organ weight and histopathologic examination of the adrenal glands and other related organs, should be carefully monitored and evaluated. During evaluation, the following should also be taken into account: (1) species, sex and age of animals used, (2) metabolic activation by a cytochrome P450 enzyme(s) and (3) physicochemical properties and the metabolic pathway of the test article. In this review, we describe the following crucial points for toxicologic pathologists to consider when evaluating adrenal toxicity: functional anatomy, blood supply, hormone production in each compartment, steroid biosynthesis, potential medulla-cortex interaction, and species and gender differences in anatomical features and other features of the adrenal gland which could affect vulnerability to toxic effects. Finally practical approaches for evaluating adrenal toxicity in nonclinical safety studies are discussed.

Journal

• Journal of Toxicologic Pathology

  Journal of Toxicologic Pathology 28 (3), 125-132, 2015

  JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY

Keywords

• adrenal cortex
• adrenal medulla
• nonclinical toxicity
• species differences
• steroidogenesis

Details

• CRID: 1390282679392077696
• NII Article ID: 130005090419
• NII Book ID: AN10232280
• DOI: 10.1293/tox.2015-0025
• ISSN: 1881915X
• ISSN: 09149198
• NDL BIB ID: 026690641
• Web Site: http://id.ndl.go.jp/bib/026690641
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026690641
• Web Site: https://www.jstage.jst.go.jp/article/tox/28/3/28_2015-0025/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016141755
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed