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Record W4406715359 · doi:10.1016/j.fct.2025.115277

A proposed screening strategy for evaluating the genotoxicity potential of botanicals and botanical extracts

2025· review· en· W4406715359 on OpenAlexaff
Kristine L. Witt, Jan van Benthem, Tetyana Kobets, Guosheng Chen, O Kelber, Julie Krzykwa, James T. MacGregor, Nan Mei, Constance A. Mitchell, Ivonne M.C.M. Rietjens, Zehra Sarigol-Kilic, Stephanie L. Smith‐Roe, Helga Stopper, Yax Thakkar, Errol Zeiger, Stefan Pfuhler

Bibliographic record

VenueFood and Chemical Toxicology · 2025
Typereview
Languageen
FieldPharmacology, Toxicology and Pharmaceutics
TopicDrug-Induced Hepatotoxicity and Protection
Canadian institutionsHealth Canada
FundersNational Institute of Environmental Health SciencesU.S. Food and Drug AdministrationU.S. Department of Health and Human ServicesNational Institutes of HealthEuropean Food Safety AuthorityHealth and Environmental Sciences Institute
KeywordsGenotoxicityCAS Registry NumberTraditional medicineChemistryPharmacologyComputational biologyToxicologyBiologyMedicineToxicityOrganic chemistry

Abstract

fetched live from OpenAlex

Botanicals have long been used to promote health and treat diseases, but the safety of many currently marketed botanicals has not been adequately evaluated. Given the chemical complexity of botanicals, which often contain numerous unknown constituents, and their widespread use, comprehensive toxicity assessments are needed. The Botanical Safety Consortium was established to address this challenge. This international group of experts in toxicology, chemistry, bioinformatics, and pharmacognosy is developing a toolkit of assays to generate reliable toxicological profiles for botanicals. Genotoxicity assessment is especially critical, because, unlike other toxicities, genotoxicity is not adequately identified by adverse event and history-of-use reports, and genotoxicity is directly linked to health consequences such as cancer and birth defects. The Consortium's Genotoxicity Technical Working Group is exploring a genotoxicity testing strategy based on the use of in silico modeling and the bacterial reverse mutation and in vitro micronucleus assays and including several options for additional tests to further characterize genotoxicity and mode of action when indicated. The effectiveness of this testing strategy is being evaluated using 13 well-characterized botanicals with existing toxicological data as case studies. A brief overview of each of these 13 botanicals is provided. The final strategy for developing comprehensive genotoxicity profiles of botanicals will incorporate published genotoxicity data, chemical composition information, in silico and in vitro test data, and human exposure data, reducing the need for animal testing.

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)0.002
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.004
Threshold uncertainty score0.015

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.001
Meta-epidemiology (narrow)0.0020.001
Meta-epidemiology (broad)0.0010.002
Bibliometrics0.0020.001
Science and technology studies0.0010.001
Scholarly communication0.0020.001
Open science0.0020.001
Research integrity0.0020.001
Insufficient payload (model declined to judge)0.0040.004

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 head0.313
GPT teacher head0.510
Teacher spread0.197 · 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 designNot applicable
Domainnot available
GenreReview

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

Citations9
Published2025
Admission routes1
Has abstractyes

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