Olfactory toxicity of methyl iodide in the rat

Abstract

The monohalomethanes (methyl iodide, methyl bromide and methyl chloride) are widely used industrial methylating agents with pronounced acute and chronic toxicity in both experimental animals and man. Recently inhalation exposure of rats to methyl bromide has been shown to result in severe olfactory toxicity. This study examined the effects on the rat nasal cavity of inhalation of methyl iodide (100 ppm for 0.5-6 h), and demonstrated that methyl iodide is a more potent olfactory toxin than methyl bromide. Within the nasal cavity the olfactory epithelium was the principle target tissue, and it was only at high doses (600 ppm.h) that limited damage to transitional epithelium occurred. The squamous and respiratory epithelia were consistently unaffected. Within olfactory epithelium the sustentacular cells were the primary cellular target and damage to sensory cells appeared to be a secondary event. Methyl iodide induced olfactory damage was reversible, and 2 weeks after exposure almost complete repair had taken place.

Heat shock protein 70 in the rat nasal cavity: localisation and response to hyperthermia

“…A wide variety of compounds cause toxicity within the nasal cavity, including environmental pollutants (Turk et al 1987;Johnson et al 1990;Bascom et al 1995), industrial chemicals (Gaskell et al 1988;Keenan et al 1990;Reed et al 1995;Morgan 1997), herbicides (Brandt et al 1990; Morgan et al 1997), wood dust (Feron et al 2001) and drugs (Johansson 1981;Hart et al 1995). Thus, the nasal passages are now routinely investigated during toxicity studies, and there is a need for robust in vitro model systems for screening for nasal toxins.…”

Three-Dimensional Mapping of the Lesions Induced by β-β'-Iminodiproprionitrile, Methyl Iodide and Methyl Methacrylate in the Rat Nasal Cavity

“…Exposure levels that caused moderate, well-defined degeneration within the nasal cavity were required, and were chosen based on preliminary dose-ranging studies. Both the nature and the severity of the nasal lesions in rats exposed to MeI or MMA were as described by Reed et al (32) and Hext et al (14,15), respectively (Figures 1, 3, and 4). Similarly, the morphological changes reported in this study following administration of IDPN are identical to those described by Genter et al (12) (Figure 2).…”

“…The aim of this work was not to uncover new aspects regarding the toxicity of the 3 chosen compounds, but to map in more detail, and in 3D, the distribution of nasal lesions that have already been documented in the literature (12,14,15,32). Exposure levels that caused moderate, well-defined degeneration within the nasal cavity were required, and were chosen based on preliminary dose-ranging studies.…”

“…For the purposes of this study moderate nasal toxicity that would result in a relatively focal lesion was required, and these dose levels were chosen based on the literature (12,14,32) and preliminary dose-ranging studies. Rats were administered a single IP injection of β-β -iminodipropionitrile (IDPN, 150 mg/ml/kg in saline, n = 3) or saline alone (1 ml/kg, n = 3) and killed 24 hours after dosing.…”

“…Other animals were exposed by nose-only inhalation to either 400 ppm methyl methacrylate (MMA) for 4 hours, 100 ppm methyl iodide (MeI) for 2 hours, or clean, dry air for 6 hours (n = 3 for each exposure group), and sacrificed 24 hours after the end of the exposures. The test atmospheres were generated by evaporating the compounds inside a condenser and diluting the resultant vapours with clean dry air to obtain the target concentration (14,32). Test atmospheres were sampled regularly during the exposure period using a gas-tight syringe, and analysed on a gas chromatograph (Hewlett Packard, HP5890 Series II) fitted with a 25 m × 530 µm CPSIL5CB (Chrompak) column and a flame ionisation detector.…”