Methyl isocyanate eight-day vapor inhalation study with Fischer 344 rats.

Abstract

Groups of ten male and ten female Fischer 344 rats were exposed by inhalation3.1, 0.6, 0.15, or 0.0 (control) ppm of methyl isocyanate (MIC) vapor 6 hr per day for 8 days (two 4-day sessions separated by a 2-day rest). Evaluation of toxic effects included body weight, food consumption, organ weights, and selected hematologic, ophthalmic, neurologic, gross anatomic, and histologic examinations. There were no deaths during the study. Rats of the 3.1 ppm exposure group had decreased body weights, food consumption, and blood oxygen saturation (males only). An increase in hemoglobin concentration (males only) and in lung weights (absolute and as a percentage of body weight) were also observed in the 3.1 ppm rats. Ophthalmic or neurofunctional behavior evaluations were negative for all MIC exposure groups.Only 3.1 ppm of MIC vapor resulted in lesions in the respiratory tract, 0.6 or 0.15 ppm did not. The types of lesions observed were inflammation and squamous metaplasia in the nasal cavity, trachea, and bronchi; inflammation of the bronchioles and alveoli; and submucosal fibroplasia of the bronchioles. No significant lesions were observed in tissues other than those of the respiratory tract in all MIC exposure groups. The results of this study indicate the current 0.02 ppm threshold limit value for MIC is not too high regarding toxicity.

Biological effects of short-term, high-concentration exposure to methyl isocyanate. V. Morphologic evaluation of rat and guinea pig lungs.

“…Therefore, the intraluminal airway fibrosis described in rats and mice earlier (1)(2)(3)(4) and in other studies (12) was not observed. We can speculate that, had animals been allowed to survive, reparative processes would have occurred, some of which would have produced fibrosis.…”

“…We have shown previously that MIC vapor exposure to rats, mice, and guinea pigs in a single 6-hr exposure (1,2), as well as repeated 6-hr exposures of rats (3,4), resulted in marked epithelial necrosis in the upper respiratory tract, including the nasal passages, larynx, and trachea. Even higher exposure concentrations, albeit for shorter periods, would be expected to result in exfoliation or sloughing of epithelium from these areas, leading to further blockage of the airways as a result of aspiration.…”

“…These studies, designed to complement the studies being conducted by NTP of NIEHS (see papers in this issue), concentrated on short exposure to high vapor concentrations of MIC in the two species which had proven most sensitive in previous studies, and in which qualitative morphologic differences had been found, namely, the rat and guinea pig (1,2). Much of our previous work indicated that the principal region affected following either single or repeated 6-hr the mucosa of the upper respiratory tract, as well as the conducting airways of the lung (1)(2)(3)(4). Consequently, we elected to focus attention on the morphologic changes induced by MIC on the conducting airways of the lung, as well as on the pulmonary parenchyma, or gas exchange regions.…”

Biological Effects of Short-Term, High-Concentration Exposure to Methyl Isocyanate. I. Study Objectives and Inhalation Exposure Design

“…A discussion of the results of these MIC studies have been included in this issue of Environmental Health Perspectives (7)(8)(9). There was good agreement between the results of the studies performed in the 1960s and the studies conducted in the 1980s (4).…”

Eighty-five day postexposure follow-up study in Fischer 344 rats after repeated exposures to methyl isocyanate vapor.

“…MIC vapor was determined to be a potent irritant, resulting in extensive damage to the respiratory mucosa in Fischer 344 rats, B6C3F1 mice, and Hartley guinea pigs (2,3). Subsequently, a repeated exposure study was conducted in which groups of male and female F344 rats were exposed to 3.1, 0.6, 0.15, or 0.0 (control) ppm of MIC vapor 6 hr per day for two 4-day periods separated by a 2-day rest (4,5). Only the 3.1 ppm exposure regimen resulted in biologically significant changes, and these were confined to the respiratory tract.…”