Quantitative Systems Toxicology (DILIsym) Modeling of the Acetaminophen (Paracetamol) Mode of Action (MOA) Pathway for Hepatotoxicity Supports That Acetaminophen is Not a Carcinogenic hHazard in Humans

Authors: Howell BA, Yang K, Gebremichael Y, Eichenbaum G
Conference: AAPS
Keywords: acetaminophen, carcinogenicity, DILIsym, hepatotoxicity, liver injury, OEHHA, Office of Environment Health Hazard Assessment, QST modeling
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Purpose

  • Acetaminophen has a long history of safe use at therapeutic doses, but can cause liver injury at very high doses
  • The California Office of Environment Health Hazard Assessment (OEHHA) recently called for a scientific review of the carcinogenicity hazard potential of acetaminophen
  • This Quantitative Systems Toxicology work supported this review as part of a broader scientific weight-of-evidence assessment of the carcinogenicity hazard potential of acetaminophen

By Brett A. Howell, Kyunghee Yang, Yeshi Gebremichael, Gary Eichenbaum

2020 AAPS Annual Meeting PharmSci 360, Oct. 26- Nov. 5, 2020