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

Toxicological sciences : an official journal of the Society of Toxicology·2026
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Related Experiment Video

Updated: Jul 16, 2026

Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter
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Investigation of Ethylene Oxide Genotoxicity Dose-Response to Inform Cancer Risk Assessment.

B Bhaskar Gollapudi1, James E Bus2, Phillip Cassidy3

  • 1Consulting Toxicologist, Midland, Michigan, USA.

Environmental and Molecular Mutagenesis
|July 15, 2026
PubMed
Summary

Ethylene oxide (EtO) is a weak genotoxicant, with genetic damage observed mainly at high concentrations. This supports a linear dose-response model for EtO carcinogenicity, crucial for accurate cancer risk assessment.

Keywords:
B6C3F1 miceerythrocytesinhalationmicronucleuspig‐a mutation

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Published on: March 24, 2020

Area of Science:

  • Toxicology
  • Genetics
  • Risk Assessment

Background:

  • Ethylene oxide (EtO) is an alkylating agent linked to carcinogenicity in rodents and humans.
  • Its mode of action for cancer is postulated to be DNA reactivity.
  • Understanding EtO's genotoxic dose-response is key for cancer risk assessment.

Purpose of the Study:

  • To investigate the dose-response relationship for ethylene oxide-induced genetic damage.
  • To assess the biological plausibility of a linear dose-response model for EtO carcinogenicity.

Main Methods:

  • Male and female B6C3F1 mice were exposed to varying concentrations of EtO via inhalation for 28 days.
  • Mutagenicity was assessed using the Pig-a gene mutation assay in reticulocytes and red blood cells.
  • Cytogenetic damage was evaluated using the erythrocyte micronucleus test.

Main Results:

  • Ethylene oxide demonstrated weak genotoxicity, with significant increases in Pig-a and micronucleus frequencies observed primarily at 200 ppm.
  • The dose-response for genetic damage showed a 'hockey-stick' shape.
  • A conservative interpretation suggests a linear response across the exposure range.

Conclusions:

  • A single, shallow linear slope dose-response model is biologically plausible for EtO carcinogenicity.
  • This model is consistent with a mutagenic mode of action for ethylene oxide.
  • Findings support refining cancer risk assessment for ethylene oxide exposure.