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Published on: July 10, 2018
Evaluation of respiratory parameters in rats and rabbits exposed to methyl iodide
Michael P DeLorme1, Mathew W Himmelstein, Raymond A Kemper
1DuPont Haskell Global Centres for Health and Environmental Sciences, Newark, Delaware 19714-0050, USA.
Abstract:
Laboratory animals exposed to methyl iodide (MeI) have previously demonstrated lesions of the olfactory epithelium that were associated with local metabolism in the nasal tissues. Interactions of MeI in the nasal passage may, therefore, alter systemic toxicokinetics. The current study used unrestrained plethysmographs to determine the MeI effect on the breathing frequency and minute volume (MV) in rats and rabbits. Groups of 4 rats each were exposed to 0, 25, or 100 ppm and groups of 4 rabbits each were exposed to 0 and 20 ppm MeI for 6 h. Breathing frequency and MV were measured and recorded during the exposure. Blood samples were collected for inorganic serum iodide and the globin adduct S-methylcysteine (SMC) as biomarkers of systemic kinetics immediately following exposure. No significant reductions in breathing frequency were observed for either rats or rabbits. Significant changes in minute volume were demonstrated by both rats and rabbits; however, the changes observed in rats were not concentration dependent. The MeI-induced changes in MV resulted in significant differences in the total volume of test substance atmosphere inhaled over the 6-h period. Rats demonstrated a concentration-dependent increase in both inorganic serum iodide and SMC. Rabbits exposed to 20 ppm MeI demonstrated a significant increase of inorganic serum iodide; SMC was also increased but was not statistically significant. The results of this study are consistent with previous kinetic studies with MeI, and the data presented here can be integrated into a computational fluid dynamics physiologically based pharmacokinetic model for both rats and rabbits.
Insights
Methyl iodide (MeI) inhalation alters breathing patterns in rats and rabbits, affecting total inhaled dose. Biomarkers indicate systemic absorption and metabolism following MeI exposure.
Area of Science:
- Toxicology
- Pharmacokinetics
- Respiratory Physiology
Background:
- Nasal lesions from methyl iodide (MeI) exposure suggest local metabolism impacts systemic toxicokinetics.
- Understanding MeI's respiratory effects is crucial for assessing its overall toxicity.
Purpose of the Study:
- To investigate the effects of methyl iodide (MeI) on respiratory parameters (breathing frequency, minute volume) in rats and rabbits.
- To measure systemic biomarkers of MeI exposure, including inorganic serum iodide and S-methylcysteine (SMC).
Main Methods:
- Rats and rabbits were exposed to varying concentrations of MeI (0-100 ppm) for 6 hours in unrestrained plethysmographs.
- Breathing frequency and minute volume were continuously monitored.
- Blood samples were analyzed for inorganic iodide and SMC levels post-exposure.
Main Results:
- No significant changes in breathing frequency were observed in either species.
- Minute volume significantly changed in both rats and rabbits, influencing total inhaled MeI dose.
- Rats showed a concentration-dependent increase in serum iodide and SMC; rabbits showed increased iodide but not statistically significant SMC.
Conclusions:
- Methyl iodide exposure alters respiratory minute volume, impacting inhaled dose and systemic kinetics.
- Biomarkers confirm systemic absorption of MeI in both species.
- Data supports integration into physiologically based pharmacokinetic models for MeI.
