Evidence map›Paper›PMID 29113941›Full record

ReviewRegulatory toxicology and pharmacology : RTP2018

Human relevance of rodent liver tumors: Key insights from a Toxicology Forum workshop on nongenotoxic modes of action.

Susan P Felter, Jennifer E Foreman, Alan Boobis, J Christopher Corton, Adriana M Doi, Lynn Flowers, Jay Goodman, Lynne T Haber, Abigail Jacobs, James E Klaunig and 3 more

Open access · hybridAbstract readReview
In one paragraph

Review in Regulatory toxicology and pharmacology : RTP, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Integration of mechanistic and repeat dose toxicity data in the derivation of an oral reference dose for HFPO-DA.Toxicological sciences : an official journal of the Society of Toxicology · 2026
    Review
  6. Article
  7. Article
  8. Review
  9. Dose-response modeling of effects in mice after exposure to a polyfluoroalkyl substance (Nafion byproduct 2).Toxicological sciences : an official journal of the Society of Toxicology · 2025
    Article
  10. Article
  11. Article
  12. Environmental consequences of interacting effects of changes in stratospheric ozone, ultraviolet radiation, and climate: UNEP Environmental Effects Assessment Panel, Update 2024.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2025
    Article
  13. Review
  14. The MAK collection for occupational health and safety · 2024
    Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Computational toxicology (Amsterdam, Netherlands) · 2021
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 11 institutions in 3 countries.

Susan P FelterProcter and Gamble, Central Product Safety, Mason, OH, United States. Electronic address: Felter.sp@pg.com.
Jennifer E ForemanExxonMobil Biomedical Sciences, Inc., Annandale, NJ, United States.
Alan BoobisDepartment of Medicine, Imperial College London, London, UK.
J Christopher CortonNational Health and Environmental Effects Research Lab, US EPA, Durham, NC, United States.
Adriana M DoiBASF Corporation, Research Triangle Park, NC, United States.
Lynn FlowersOffice of Science Policy, US EPA, Washington DC, United States.
Jay GoodmanMichigan State University, Dept. Pharmacology and Toxicology, East Lansing, MI, United States.
Lynne T HaberRisk Science Center, Dept. of Environmental Health, University of Cincinnati, Cincinnati, OH, United States.
Abigail JacobsCenter for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States.
James E KlaunigIndiana University, Bloomington, IN, United States.
Angela M LynchToxPlus Consulting, LLC, Haymarket, VA, United States.
Jonathan MoggsNovartis Institutes for BioMedical Research, Preclinical Safety, Translational Medicine, Basel, Switzerland.
Arun PandiriNational Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, United States.
Environmental Protection Agency · USBASF (United States) · USExxonMobil (United States) · USImperial College London · GBIndiana University Bloomington · USMichigan State University · USNational Institute of Environmental Health Sciences · USNovartis (Switzerland) · CHProcter & Gamble (United States) · USUnited States Food and Drug Administration · USUniversity of Cincinnati · US

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

The Toxicology Forum sponsored a workshop in October 2016, on the human relevance of rodent liver tumors occurring via nongenotoxic modes of action (MOAs). The workshop focused on two nuclear receptor-mediated MOAs (Constitutive Androstane Receptor (CAR) and Peroxisome Proliferator Activated Receptor-alpha (PPARα), and on cytotoxicity. The goal of the meeting was to review the state of the science to (1) identify areas of consensus and differences, data gaps and research needs; (2) identify reasons for inconsistencies in current regulatory positions; and (3) consider what data are needed to demonstrate a specific MOA, and when additional research is needed to rule out alternative possibilities. Implications for quantitative risk assessment approaches were discussed, as were implications of not considering MOA and dose in hazard characterization and labeling schemes. Most, but not all, participants considered the CAR and PPARα MOAs as not relevant to humans based on quantitative and qualitative differences. In contrast, cytotoxicity is clearly relevant to humans, but a threshold applies. Questions remain for all three MOAs concerning what data are necessary to determine the MOA and to what extent it is necessary to exclude other MOAs.

Indexed as

AnimalsConstitutive Androstane ReceptorHumansLiverLiver NeoplasmsPPAR alphaReceptors, Cytoplasmic and NuclearRisk AssessmentRodentiaConstitutive Androstane ReceptorPPAR alphaReceptors, Cytoplasmic and NuclearConstitutive Androstane ReceptorMode of actionNongenotoxicPeroxisome proliferator-activated receptor alpha (PPARα)Rodent liver tumors

Identifiers

PMID29113941
PMCPMC11350555
OpenAlexW2765816881

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.