Two-day inhalation toxicity study of methyl iodide in the rat.

The effects of inhaled methyl iodide (MeI) on clinical pathology parameters, glutathione (GSH) tissue levels, serum thyroid hormone and inorganic iodide concentrations, S-methylcysteine hemoglobin concentrations, and liver UDP-glucuronyltransferase activity were studied in the rat. Male rats were exposed by whole-body inhalation to 0, 25, or 100 ppm MeI, 6 h/day for up to 2 days. Serum cholesterol concentrations (both high-density lipoprotein [HDL] and low-density lipoprotein [LDL] fractions) were increased and triglycerides were decreased at both exposure levels. Serum thyroid-stimulating hormone (TSH) concentrations were increased at 25 and 100 ppm, and serum triiodothyronine (T(3)) and thyroxine (T(4)) concentrations were decreased at 100 ppm. There was no change in either reverse triiodothyronine (rT(3)) or UDP-glucuronyltransferase activity at either exposure level. A dose- and time-dependent reduction in GSH levels in blood, kidney, liver, and nasal tissue was observed, with the greatest reduction in nasal tissue (olfactory and respiratory epithelium). MeI exposure also resulted in a substantial dose- and time-dependent increase in both serum inorganic iodide and red blood cell S-methylcysteine hemoglobin adducts. These results indicate that following inhalation exposure, MeI is rapidly metabolized in blood and tissue of rats, resulting in methylation products and release of inorganic iodide.

Evaluation of respiratory parameters in rats and rabbits exposed to methyl iodide.

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.