Key Characteristics of Human Hepatotoxicants as a Basis for Identification and Characterization of the Causes of Liver Toxicity

Details

• Journal Article:
  Hepatology
• Personal Author:
  Rusyn, Ivan ; Arzuaga, Xabier ; Cattley, Russell C. ; Corton, J. Christopher ; Ferguson, Stephen S. ; Godoy, Patricio ; Guyton, Kathryn Z. ; Kaplowitz, Neil ; Khetani, Salman R. ; Roberts, Ruth A. ; Roth, Robert A. ; Smith, Martyn T.
• Description:
  Hazard identification regarding adverse effects on the liver is a critical step in safety evaluations of drugs and other chemicals. Current testing paradigms for hepatotoxicity rely heavily on preclinical studies in animals and human data (epidemiology and clinical trials). Mechanistic understanding of the molecular and cellular pathways that may cause or exacerbate hepatotoxicity is well advanced and holds promise for identification of hepatotoxicants. One of the challenges in translating mechanistic evidence into robust decisions about potential hepatotoxicity is the lack of a systematic approach to integrate these data to help identify liver toxicity hazards. Recently, marked improvements were achieved in the practice of hazard identification of carcinogens, female and male reproductive toxicants, and endocrine disrupting chemicals using the key characteristics approach. Here, we describe the methods by which key characteristics of human hepatotoxicants were identified and provide examples for how they could be used to systematically identify, organize, and use mechanistic data when identifying hepatotoxicants. [Description provided by NIOSH]
• Subjects:
  Animals Hazardous Substances Hepatotoxicity Liver Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Hazard identification; Hazard labels; Hepatotoxins; Liver damage; Molecular biology; Toxic effects; Exposure limits; Cellular function; Cell signaling; Hazardous drugs; Chemical hazards
• Source:
  Hepatology 2021 Dec; 74(6):3486-3496
• ISSN:
  0270-9139
• Pubmed ID:
  34105804
• Pubmed Central ID:
  PMC8901129
• Document Type:
  Text
• Funding:
  P42 ES004705/ES/NIEHS NIH HHSUnited States/ ; P42 ES027704/ES/NIEHS NIH HHSUnited States/ ; T42 OH008429/OH/NIOSH CDC HHSUnited States/ ; Z99 ES999999/ImNIH/Intramural NIH HHSUnited States/
• Genre:
  Journal Article
• Place as Subject:
  Alabama ; California ; District of Columbia ; Illinois ; Michigan ; North Carolina ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 5 ; OSHA Region 6 ; OSHA Region 9 ; Texas
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  19 pdf pages
• Volume:
  74
• Issue:
  6
• NIOSHTIC Number:
  nn:20065606
• Contact Point Address:
  Ivan Rusyn, M.D., Ph.D., Department Veterinary Integrative Biosciences, 4458 TAMU, Texas A&M University, College Station, TX 77845
• Email:
  irusyn@tamu.edu
• Federal Fiscal Year:
  2022
• Performing Organization:
  University of California, Berkeley
• Peer Reviewed:
  True
• Collection(s):
  National Institute for Occupational Safety and Health CDC Public Access
• Main Document Checksum:
  urn:sha-512:c2d453ffce68faf4adf30c9dd2a4a5fbb09441fce63b5a24ccedb002eddd49a087a620673dd08e680a9d1186f891061fcf462817a85ef44b537a2d29ed5081f9
• Download URL:
  https://stacks.cdc.gov/view/cdc/115436/cdc_115436_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]