• PRODUCTS
    • Assay Kit Platform & Formats
    • All Receptor Assays
    • Environmental Monitoring Assays
    • Growth Factor Assays
    • Ortholog Receptor Assays
    • Toxicology Assays
      • In Vitro Hepatotoxicity Assay Kit
      • Gene Expression Profiling Assay Kit
      • P-gp/MDR1 Drug Interaction Assay Kit
    • INDIGlo Luciferase Detection Reagent
    • Live Cell Multiplex
  • SERVICES
    • Reporter Assay Services
    • Nuclear Hormone Receptor Profiling
    • Environmental Monitoring Services
    • Gene Expression Profiling Services
    • In Vitro Hepatotoxicity Screening Services
    • Custom Assay Development
  • APPLICATIONS
    • Drug Discovery
    • Discovery Toxicology
    • Disease States
      • Overview
      • Anemia & Kidney Disease
      • Autoimmune Disease & Inflammation
      • Cancer
      • Cardiovascular Disease
      • Diabetes
      • Endocrinology
      • NAFLD/NASH
      • Obesity
    • Environmental Monitoring Applications
  • RESOURCES
    • Nuclear Receptor Overview
    • Webinars and Publications
      • New Research Publications
      • Webinars from INDIGO
      • Scientific Whitepapers from INDIGO
      • Scientific Posters from INDIGO
      • BLOG
    • Product Literature
      • INDIGO Technical Manuals
      • Product SDS
      • upcyte® Hepatocytes
    • FAQ
  • ABOUT
    • About INDIGO
    • Why INDIGO
    • Key Personnel
      • Board of Directors & Advisors
      • Management
    • Employment
    • INDIGO Press Releases
    • INDIGO in the News
  • CONTACT
    • Contact INDIGO
    • Request a Quote
    • Ordering & Distributors
Search site...

± α β γ δ Δ ε ζ κ ω ö ® ™ µ

  • PRODUCTS
    • Assay Kit Platform & Formats
    • All Receptor Assays
    • Environmental Monitoring Assays
    • Growth Factor Assays
    • Ortholog Receptor Assays
    • Toxicology Assays
      • In Vitro Hepatotoxicity Assay Kit
      • Gene Expression Profiling Assay Kit
      • P-gp/MDR1 Drug Interaction Assay Kit
    • INDIGlo Luciferase Detection Reagent
    • Live Cell Multiplex
  • SERVICES
    • Reporter Assay Services
    • Nuclear Hormone Receptor Profiling
    • Environmental Monitoring Services
    • Gene Expression Profiling Services
    • In Vitro Hepatotoxicity Screening Services
    • Custom Assay Development
  • APPLICATIONS
    • Drug Discovery
    • Discovery Toxicology
    • Disease States
      • Overview
      • Anemia & Kidney Disease
      • Autoimmune Disease & Inflammation
      • Cancer
      • Cardiovascular Disease
      • Diabetes
      • Endocrinology
      • NAFLD/NASH
      • Obesity
    • Environmental Monitoring Applications
  • RESOURCES
    • Nuclear Receptor Overview
    • Webinars and Publications
      • New Research Publications
      • Webinars from INDIGO
      • Scientific Whitepapers from INDIGO
      • Scientific Posters from INDIGO
      • BLOG
    • Product Literature
      • INDIGO Technical Manuals
      • Product SDS
      • upcyte® Hepatocytes
    • FAQ
  • ABOUT
    • About INDIGO
    • Why INDIGO
    • Key Personnel
      • Board of Directors & Advisors
      • Management
    • Employment
    • INDIGO Press Releases
    • INDIGO in the News
  • CONTACT
    • Contact INDIGO
    • Request a Quote
    • Ordering & Distributors

Assessment of the mode of action underlying development of liver lesions in mice following oral exposure to HFPO-DA and relevance to humans

Print Friendly, PDF & Email

ABSTRACT

HFPO-DA (ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoate) is a short-chain polyfluorinated alkyl substance (PFAS) used in the manufacture of some types of fluorinated polymers. Like many PFAS, toxicity studies with HFPO-DA indicate the liver is the primary target of toxicity in rodents following oral exposure. Due to the structural diversity of PFAS, the mode of action (MOA) can differ between PFAS for the same target tissue. There is significant evidence for involvement of peroxisome proliferator-activated receptor alpha (PPARα) activation based on molecular and histopathological responses in the liver following HFPO-DA exposure, but other MOAs have also been hypothesized based on limited evidence. The MOA underlying the liver effects in mice exposed to HFPO-DA was assessed in the context of the Key Events (KEs) outlined in the MOA framework for PPARα activator-induced rodent hepatocarcinogenesis. The first three KEs (i.e., PPARα activation, alteration of cell growth pathways, and perturbation of cell growth/survival) are supported by several lines of evidence from both in vitro and in vivo data available for HFPO-DA. In contrast, alternate MOAs, including cytotoxicity, PPARγ and mitochondrial dysfunction are generally not supported by the scientific literature. HFPO-DA-mediated liver effects in mice are not expected in humans as only KE 1, PPARα activation, is shared across species. PPARα-mediated gene expression in humans produces only a subset (i.e., lipid modulating effects) of the responses observed in rodents. As such, the adverse effects observed in rodent livers should not be used as the basis of toxicity values for HFPO-DA for purposes of human health risk assessment.

To read the article click HERE.

Date of publication: 11 January 2023; Toxicological Sciences

Author information:  Melissa M Heintz (1), Laurie C Haws (2), James E Klaunig (3), John M Cullen (4), Chad M Thompson (5)

(1) ToxStrategies, LLC, Asheville, North Carolina, USA.
(2) ToxStrategies, LLC, Austin, Texas, USA.
(3) Indiana University, School of Public Health, Bloomington, IN, USA.
(4) North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA.
(5) ToxStrategies, LLC, Katy, Texas, USA.

Search site...
Click to Insert Symbols in Search

α β γ δ Δ ε ζ κ ® ™ µ

Request a Quote

Want More Information?

Resource Quick Links

  • Technical Manuals & Product Listing
  • Safety Data Sheets
  • Sample Study Report
  • Study Work Order Form

3006 Research Drive, Suite A1, State College, PA, USA 16801

+1 (814) 234-1919

  • Terms Conditions
  • Privacy Policy
  • Product Policies
  • Limited Use Disclosure

© 2022 INDIGO Biosciences, Inc. All Rights Reserved