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Ethylene oxide dosimetry in the mouse
C D Brown1, B Asgharian, M J Turner
1Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709, USA.
Toxicology and Applied Pharmacology
|March 14, 1998
Summary
Ethylene oxide (EO) exposure shows linear blood concentrations up to 200 ppm in mice, becoming nonlinear at higher levels. Glutathione depletion likely causes this saturation, impacting dose-response models.
Area of Science:
- Toxicology
- Environmental Health
- Biochemistry
Background:
- Ethylene oxide (EO) is a mutagenic carcinogen with significant human exposure risks.
- Rodent models are crucial for understanding EO exposure-dose relationships and human risk assessment.
Purpose of the Study:
- To investigate the dosimetry of ethylene oxide in male B6C3F1 mice.
- To determine the relationship between EO exposure concentration and blood EO levels.
- To assess the role of glutathione (GSH) depletion in EO metabolism.
Main Methods:
- Direct measurement of blood EO concentrations during 4-h nose-only inhalation.
- Exposure concentrations ranged from 0 to 400 ppm.
- Measurement of GSH levels in liver, lung, kidney, and testis.
Main Results:
- Blood EO concentrations increased linearly up to 200 ppm.
- Sublinear blood dosimetry was observed above 200 ppm.
- Tissue GSH levels, particularly in liver and lung, were significantly reduced at 100 ppm EO and above.
Conclusions:
- GSH depletion is likely responsible for the nonlinear dosimetry of EO in mice.
- Findings support dose-rate effects in mice exposed to EO.
- This study refines EO exposure-dose models for improved human risk assessment.