Key Characteristics of Human Hepatotoxicants as a Basis for Identification and Characterization of the Causes of Liver Toxicity.
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
05
05
2021
received:
22
03
2021
accepted:
07
06
2021
pubmed:
10
6
2021
medline:
20
1
2022
entrez:
9
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34105804
doi: 10.1002/hep.31999
pmc: PMC8901129
mid: NIHMS1779672
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3486-3496Subventions
Organisme : NIEHS NIH HHS
ID : P42 ES004705
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES027704
Pays : United States
Organisme : NIOSH CDC HHS
ID : T42 OH008429
Pays : United States
Organisme : Intramural NIH HHS
ID : Z99 ES999999
Pays : United States
Informations de copyright
© 2021 by the American Association for the Study of Liver Diseases.
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