Registration Dossier
Registration Dossier
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EC number: 200-819-5 | CAS number: 74-88-4
Endpoint summary
Administrative data
Link to relevant study record(s)
Description of key information
Key value for chemical safety assessment
Additional information
The absorption, distribution metabolism and excretion of [14C] iodomethane has been studied following oral administration at 1.0-1.7 and 21-35 mg/kg and inhalation exposure at 21-25 and 209-250 ppm for 6 hours in male and female rats and Iodomethane was completely absorbed in both sexes following exposure by either route and metabolism and excretion were rapid. The major metabolite was carbon dioxide accounting for approximately 40-74% of the dose but significant amounts of S-methyl glutathione and N-(methylthioacetyl)glycine were also formed and eliminated in urine. A number of other metabolites, formed by further metabolism of S-methyl glutathione and N-(methylthioacetyl)glycine, were also present in urine but only as small percentages of the dose. Metabolism and excretion were unaffected by the route of exposure or the dose over the range used. Radioactivity from [14C] iodomethane was detected in tissues and blood at all times after exposure, but as radioactivity entered the one carbon pool it was incorporated into endogenous metabolites and residues would be expected.
The importance of glutathione in the metabolism of iodomethane was confirmed in an additional study in which male rats were exposed to 0, 25 and 100 ppm iodomethane by inhalation for 6 hours per day for 2 days. Dose and time dependent reductions in glutathione concentrations were found in olfactory and respiratory tissue and to a lesser extent in blood, liver and kidney. S-methyl cysteine adducts were also detected in haemoglobin showing that iodomethane had also methylated thiol groups in globin. Serum iodide concentrations were also elevated and were at maximum at the end of both exposure periods which is consistent with a rapid rate of metabolism of iodomethane.
Limited data suggest that the metabolism of iodomethane is qualitatively similar in rabbits and rats. Maternal and foetal iodide concentrations were also elevated in rabbits exposed to 20 and 25 ppm iodomethane. The increase occurred rapidly and increased with the duration of exposure. Iodide concentrations in the serum of the foetuses was higher than in the does but the concentration of S-methyl cysteine adducts in haemoglobin was comparable. The glutathione concentration was decreased in maternal liver and in foetal blood but the concentration in foetal liver was unaffected by exposure. These decreases in glutathione suggest that in pregnant rabbits iodomethane is metabolised in the maternal liver and perhaps maternal and foetal blood.
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