Evidence map›Paper›PMID 42384196›Full record

ArticleArchives of toxicology2026

Molecular dosimetry of hemoglobin adducts in mice exposed to ethylene oxide.

Chih-Wei Liu, Jiahao Feng, Jingya Peng, Haoduo Zhao, Xueying Wang, B Bhaskar Gollapudi, Abby A Li, James S Bus, Christopher Kirman, Kun Lu

Abstract read
PubMed Publisher
In one paragraph

Article in Archives of toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Chih-Wei Liu *Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jiahao Feng *Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Jingya PengDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Haoduo ZhaoDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Xueying WangDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
B Bhaskar GollapudiToxicology Consultant, Midland, MI, USA.
Abby A LiExponent, Inc. Health Sciences, Menlo Park, CA, USA.
James S BusExponent, Inc. Health Sciences, Menlo Park, CA, USA.
Christopher KirmanSciPinion, Bozeman, MT, USA.
Kun LuDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. kunlu@unc.edu.ORCID http://orcid.org/0000-0002-8125-2394

Funding

UNC Center for Environmental Health and Susceptibility P30-ES779010126UNC Superfund Research Program P42ES031007
6 · The paper itself

Abstract

Ethylene oxide (EtO) is a widely used industrial compound with known carcinogenic potential in humans. Due to its high reactivity and short biological half-life, occupational exposure assessments (> 1 ppm) rely on the detection of stable biomarkers, such as N-(2-hydroxyethyl)-L-valine (HE-V), formed as hemoglobin adducts in blood. Existing analytical methods for HE-V detection often require large volumes of blood and purified hemoglobin due to limited sensitivity, restricting their application in characterizing the dose-response relationship between EtO exposure and HE-V accumulation-particularly at low environmental exposure levels relevant to assessing potential general population health risks. In this study, we aimed to characterize the molecular dosimetry of HE-V formation in B6C3F1 mice exposed by whole body inhalation to a broad range of concentrations of EtO: 0, 0.05, 0.1, 0.5, 1, 50, 100, and 200 ppm, 7 days/week for 4 weeks. To achieve this, we developed a sensitive LC-MS-based workflow for HE-V quantification, incorporating hemoglobin purification, HE-V release plus enrichment, and targeted mass spectrometric detection from as little as 10 μL of blood and 50 μg of extracted hemoglobin. A clear, dose-dependent increase in HE-V levels was observed following EtO exposure, with statistically significant elevations detected even at 0.05 ppm compared to endogenous background levels. At lower concentrations (0.5 to 1 ppm), HE-V levels increased linearly with dose, while higher concentrations (50 to 200 ppm) exhibited an upward-bending (increasing slope) dose response. No sex-specific differences were observed. Taken together, these findings indicate EtO exhibits linear systemic toxicokinetics at lower exposures that transition to nonlinear toxicokinetics in the range of higher exposures (likely due to saturation of glutathione-mediated detoxification), thus providing new quantitative insights to support improved risk assessments and toxicological evaluations of EtO exposure.

Indexed as

Dose–response relationshipEthylene oxideHemoglobin adductMass spectrometryN-(2-hydroxyethyl)-L-valine

Identifiers

PMID42384196

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.