Evidence map›Paper›PMID 34850242›Full record

ArticleToxicological sciences : an official journal of the Society of Toxicology2022

The Effects of Benoxacor on the Liver and Gut Microbiome of C57BL/6 Mice.

Derek Simonsen, Nicole Cady, Chunyun Zhang, Rachel L Shrode, Michael L McCormick, Douglas R Spitz, Michael S Chimenti, Kai Wang, Ashutosh Mangalam, Hans-Joachim Lehmler

Abstract read
In one paragraph

Article in Toxicological sciences : an official journal of the Society of Toxicology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

4 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. A systematic review of herbicide safener toxicity.Critical reviews in toxicology · 2024
    Pooled it
  2. Review
  3. Article
  4. 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

10 authors.

Derek SimonsenDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa 52242, USA.
Nicole CadyDepartment of Pathology, The University of Iowa, Iowa City, Iowa 52242, USA.
Chunyun ZhangDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa 52242, USA.
Rachel L ShrodeDepartment of Informatics, The University of Iowa, Iowa City, Iowa 52242, USA.
Michael L McCormickFree Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa 52242, USA.
Douglas R SpitzFree Radical and Radiation Biology Program, Department of Radiation Oncology, The University of Iowa, Iowa City, Iowa 52242, USA.ORCID 0000-0002-1254-8765
Michael S ChimentiIowa Institute of Human Genetics, Carver College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA.
Kai WangDepartment of Biostatistics, The University of Iowa, Iowa City, Iowa 52242, USA.
Ashutosh MangalamDepartment of Pathology, The University of Iowa, Iowa City, Iowa 52242, USA.
Hans-Joachim LehmlerDepartment of Occupational and Environmental Health, The University of Iowa, Iowa City, Iowa 52242, USA.ORCID 0000-0001-9163-927X

Funding

Viral VectorP30CA086862 · NCI · UNIVERSITY OF IOWA · PI Christopher K Laubenthal · 2000 to 2026
$70.0M
Pulmonary Toxicology Facility CoreP30ES005605 · NIEHS · UNIVERSITY OF IOWA · PI Jong Sung Kim · 1990 to 2026
$40.5M
Project 3: MRI Imaging of Redox Active Fe Predicts GBM Responses to Pharmacological AscorbateP01CA217797 · NCI · UNIVERSITY OF IOWA · PI BUETTNER, GARRY R · 2018 to 2022
$9.6M
Multiplexed UPLC-MS/MS System for Advanced Target MetabolomicsS10OD021562 · OD · UNIVERSITY OF WASHINGTON · PI RAFTERY, DANIEL · 2016 to 2016
$596k
NCI NIH HHS P01 CA217797NCI NIH HHS P30 CA086862NIEHS NIH HHS P30 ES005605NIH HHS S10 OD021562NIOSH CDC HHS T42 OH008491
6 · The paper itself

Abstract

The toxicity of many "inert" ingredients of pesticide formulations, such as safeners, is poorly characterized, despite evidence that humans may be exposed to these chemicals. Analysis of ToxCast data for dichloroacetamide safeners with the ToxPi tool identified benoxacor as the safener with the highest potential for toxicity, especially liver toxicity. Benoxacor was subsequently administered to mice via oral gavage for 3 days at concentrations of 0, 0.5, 5, and 50 mg/kg bodyweight (b.w.). Bodyweight-adjusted liver and testes weights were significantly increased in the 50 mg/kg b.w. group. There were no overt pathologies in either the liver or the intestine. 16S rRNA analysis of the cecal microbiome revealed no effects of benoxacor on α- or β-diversity; however, changes were observed in the abundance of certain bacteria. RNAseq analysis identified 163 hepatic genes affected by benoxacor exposure. Benoxacor exposure expressed a gene regulation profile similar to dichloroacetic acid and the fungicide sedaxane. Metabolomic analysis identified 9 serum and 15 liver metabolites that were affected by benoxacor exposure, changes that were not significant after correcting for multiple comparisons. The activity of antioxidant enzymes was not altered by benoxacor exposure. In vitro metabolism studies with liver microsomes and cytosol from male mice demonstrated that benoxacor is enantioselectively metabolized by cytochrome P450 enzymes, carboxylesterases, and glutathione S-transferases. These findings suggest that the minor toxic effects of benoxacor may be due to its rapid metabolism to toxic metabolites, such as dichloroacetic acid. This result challenges the assumption that inert ingredients of pesticide formulations are safe.

Indexed as

Gastrointestinal MicrobiomeHerbicidesAnimalsLiverMaleMiceMice, Inbred C57BLOxazinesRNA, Ribosomal, 16SbenoxacorHerbicidesOxazinesRNA, Ribosomal, 16Sagrochemicalsbiotransformationchiraldose responseenvironmentalenvironmental chemicalsexposure

Identifiers

PMID34850242
PMCPMC9019840

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.