Evidence map›Paper›PMID 38157272›Full record

ArticleEnvironmental health perspectives2023

Quantitative Integration of Mode of Action Information in Dose-Response Modeling and POD Estimation for Nonmutagenic Carcinogens: A Case Study of TCDD.

Qiran Chen, Yun Zhou, Chao Ji, James E Klaunig, Kan Shao

Open access · diamondAbstract read
In one paragraph

Article in Environmental health perspectives, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

1 citing paper in PubMed, 5 citations in OpenAlex.

  1. Invited Perspective: Reference Values à la Mode of Action.Environmental health perspectives · 2023
    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

5 authors at 2 institutions in 1 country.

Qiran ChenDepartment of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, Florida, USA.
Yun ZhouDepartment of Environmental and Occupational Health, School of Public Health-Bloomington, Indiana University, Bloomington, Indiana, USA.
Chao JiDepartment of Environmental and Occupational Health, School of Public Health-Bloomington, Indiana University, Bloomington, Indiana, USA.
James E KlaunigDepartment of Environmental and Occupational Health, School of Public Health-Bloomington, Indiana University, Bloomington, Indiana, USA.
Kan ShaoDepartment of Environmental and Occupational Health, School of Public Health-Bloomington, Indiana University, Bloomington, Indiana, USA.ORCID 0000-0002-5512-2377
Indiana University Bloomington · USUniversity of Florida · US

Funding

Quantitative dose-response characterization for liver carcinogenicity with non-mutagenic modes of actionK25ES030402 · NIEHS · TRUSTEES OF INDIANA UNIVERSITY · PI SHAO, KAN · 2020 to 2024
$764k
NIEHS NIH HHS K25 ES030402
6 · The paper itself

Abstract

backgroundTraditional dose-response assessment applies different low-dose extrapolation methods for cancer and noncancer effects and assumes that all carcinogens are mutagenic unless strong evidence suggests otherwise. Additionally, primarily focusing on one critical effect, dose-response modeling utilizes limited mode of action (MOA) data to inform low-dose risk.

objectiveWe aimed to build a dose-response modeling framework that continuously extends the curve into the low-dose region via a quantitative integration of MOA information and to estimate MOA-based points of departure (PODs) for nonmutagenic carcinogens.

methods2,3,7,8-Tetrachlorodibenzo-

resultsWe identified and extracted six KQEs and corresponding essential events composing the MOA of TCDD-induced liver tumors. With the essential doses estimated from the BMD method using various settings, three link functions were applied to model the pathway dose-response relationship. Given a toxicologically plausible definition of adversity, an MOA-based POD was derived from the pathway dose-response curve. The estimated MOA-based PODs were generally comparable with traditional PODs and can be further used to calculate reference doses (RfDs).

conclusionsThe proposed framework quantitatively integrated mechanistic information in the modeling process and provided a promising strategy to harmonize cancer and noncancer dose-response assessment through pathway dose-response modeling. However, the framework can also be limited by data availability and the understanding of the underlying mechanism. https://doi.org/10.1289/EHP12677.

Indexed as

Liver NeoplasmsPolychlorinated DibenzodioxinsCarcinogensDose-Response Relationship, DrugHumansRisk AssessmentCarcinogensPolychlorinated Dibenzodioxins

Identifiers

PMID38157272
PMCPMC10756338
OpenAlexW4390414924

What OpenQuestion holds

Textmetadata
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.