MétaCan
Menu
Back to cohort

IWGT report on quantitative approaches to genotoxicity risk assessment II. Use of point-of-departure (PoD) metrics in defining acceptable exposure limits and assessing human risk

2014· article· en· W2102357766 on OpenAlexaff
James T. MacGregor, Roland Frötschl, Paul A. White, Kenny S. Crump, David A. Eastmond, Shoji Fukushima, Melanie Guérard, Makoto Hayashi, Lya G. Soeteman‐Hernández, George E. Johnson, Toshio Kasamatsu, Dan D. Levy, Takeshi Morita, Lutz Müller, Rita Schoeny, Maik J. Schuler, Véronique Thybaud

Bibliographic record

VenueMutation Research/Genetic Toxicology and Environmental Mutagenesis · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCarcinogens and Genotoxicity Assessment
Canadian institutionsHealth Canada
FundersNational Centre for the Replacement, Refinement and Reduction of Animals in ResearchSwansea UniversityBundesinstitut für Arzneimittel und Medizinprodukte
KeywordsGenotoxicityRisk assessmentToxicologyEndpoint DeterminationBiologyComputational biologyMedicineBioinformaticsComputer scienceClinical trialToxicity

Abstract

fetched live from OpenAlex

This is the second of two reports from the International Workshops on Genotoxicity Testing (IWGT) Working Group on Quantitative Approaches to Genetic Toxicology Risk Assessment (the QWG). The first report summarized the discussions and recommendations of the QWG related to the need for quantitative dose-response analysis of genetic toxicology data, the existence and appropriate evaluation of threshold responses, and methods to analyze exposure-response relationships and derive points of departure (PoDs) from which acceptable exposure levels could be determined. This report summarizes the QWG discussions and recommendations regarding appropriate approaches to evaluate exposure-related risks of genotoxic damage, including extrapolation below identified PoDs and across test systems and species. Recommendations include the selection of appropriate genetic endpoints and target tissues, uncertainty factors and extrapolation methods to be considered, the importance and use of information on mode of action, toxicokinetics, metabolism, and exposure biomarkers when using quantitative exposure-response data to determine acceptable exposure levels in human populations or to assess the risk associated with known or anticipated exposures. The empirical relationship between genetic damage (mutation and chromosomal aberration) and cancer in animal models was also examined. It was concluded that there is a general correlation between cancer induction and mutagenic and/or clastogenic damage for agents thought to act via a genotoxic mechanism, but that the correlation is limited due to an inadequate number of cases in which mutation and cancer can be compared at a sufficient number of doses in the same target tissues of the same species and strain exposed under directly comparable routes and experimental protocols.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.037
metaresearch head score (Gemma)0.027
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: none
Teacher disagreement score0.037
Threshold uncertainty score0.193

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0370.027
Meta-epidemiology (narrow)0.0040.002
Meta-epidemiology (broad)0.0020.004
Bibliometrics0.0080.005
Science and technology studies0.0010.003
Scholarly communication0.0070.004
Open science0.0060.006
Research integrity0.0050.005
Insufficient payload (model declined to judge)0.0090.008

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.100
GPT teacher head0.342
Teacher spread0.242 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designTheoretical or conceptual
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations127
Published2014
Admission routes1
Has abstractyes

Explore more

Same venueMutation Research/Genetic Toxicology and Environmental MutagenesisSame topicCarcinogens and Genotoxicity AssessmentFrench-language works237,207