A new methyl bromide gas generator for inhalation toxicity studies.

A simple generator for methyl bromide gas has been newly developed by us. For inhalation toxicity studies, until now, there have been few generators capable of producing a constant and stable concentration of methyl bromide gas easily because of its high volatility. The principle of this new generator is based on gas-liquid equilibrium. The gas is generated from the surface of liquid methyl bromide in an evaporator made of a Teflon tube. The generator can produce up to 10,000 ppm of methyl bromide gas in a 0.1 m3 exposure chamber, and the concentration of this generated gas is able to be kept within +/- 0.8% over a long period of time. The generator has proved to be useful for investigating the effects of methyl bromide on health in inhalation toxicity studies.

[Neurotoxicity of methyl bromide--neuropathologic evaluation--preliminary study].

Methyl bromide exposure produces disorders of the central and peripheral nervous system. In the literature, there are many neuropathologic studies on the nervous system, especially on the central nervous system, of experimental animals intoxicated with methyl bromide presented. However, in our opinion, a variety of lesions of the nervous system described in the human methyl bromide intoxication have not been well reproduced in the experimental animals. In this study, male Wistar rats were subjected to a 6-hour exposure a day to methyl bromide at a concentration of 500 or 290 ppm 3 days a week for 3 to 8 weeks. The systematic neuropathologic studies of their central and peripheral nervous systems were carried out to reproduce the nervous system lesions in the human methyl bromide intoxication hitherto not produced in the experimental animals. Among the rats exposed to methyl bromide at a concentration of 500 ppm for 10 to 18 days, the axonal degeneration of myelinated fibers at the cervical level of the fasciculus gracilis, which probably corresponds to the degeneration of the spinal posterior column in humans, and the necrosis of the caudate-putamen and atrophy of neurons and pallor of the neuropile in caudate-putamen, thalamus and cingulate cortex, which probably correspond to the degenerative findings of the cerebrum in humans, were found. The rats exposed to methyl bromide at a concentration of 290 ppm for 8 weeks (24 days) did not show any noticeable abnormalities histologically.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of creatine kinase activity in rat brain by methyl bromide gas.

Rats were exposed to 290 or 495 ppm methyl bromide gas for 6 h/day, 3 times/wk for 4 to 8 wk. Creatine kinase (CK), aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) activities and bromide ion concentrations were measured in eight regions of the brain. Methyl bromide gas inhibited CK activities in all regions of the brain, though the inhibition tended to be smallest in the cerebellum (hemisphere and vermis) and largest in the brainstem (hypothalamus, midbrain, and medulla oblongata). The dose of methyl bromide to inhibit CK activities was lower than that to damage the central nervous system histologically. No inhibition of ASAT or LDH activities was seen except for a slight inhibition of these in striatum. Inhibition of CK activities did not increase clearly on increasing dose (290 to 495 ppm) or on prolonging exposure period (4 to 8 wk). Although 50% recovery of CK activities and the half-life of bromide ion agreed well in the medulla oblongata, changes in CK activities and bromide ion concentrations did not correlate otherwise. Thus, inhibition of CK activities in brain appears to be a sensitive indicator of methyl bromide intoxication, and may be related to genesis of its neurotoxicity. The inhibition seems to be caused by methyl bromide itself rather than by bromide ion. When effects on enzyme activities in brain homogenate were examined in vitro by bubbling with methyl bromide gas, CK inhibition was seen within 15 s of exposure. Dithiothreitol suppressed the CK inhibition, whereas N-acetylcysteine did not. These observations suggest that methyl bromide may attack sites in the CK molecule different from those attacked by ethylene oxide or acrylamide.

[A case of bronchiolitis obliterans organizing pneumonia: diagnostic utility of bronchoalveolar lavage and CT scan].

A 54-year-old female was admitted to our hospital because of abnormal shadows on chest X-ray at annual checkup. She complained of dyspnea on exertion. Chest X-ray findings showed an increase in density at the bilateral lower lung fields and unclearness of the silhouette of the heart and the diaphragm. CT scan findings revealed irregular opacities of various density with many small cystic changes and air bronchograms and air bronchiolograms. The pulmonary function test showed restrictive ventilatory disturbance and reduced diffusing capacity. BALF findings revealed an increase in the total cell count, an increase in the percentage of lymphocytes and a decrease in the OKT4+/OKT8+ ratio. TBLB specimen showed infiltration of mononuclear cells in alveolar septa and organizing exudate in alveolar ducts. These findings suggested a diagnosis of BOOP rather than IPF, and an open lung biopsy was performed. Open lung biopsy specimen showed obstructive bronchiolitis with polypoid granulation tissue and thickening of alveolar septa with infiltration of mononuclear cells, and she was diagnosed as having BOOP. She responded well to corticosteroid and is free from any abnormalities on chest X-ray, CT scan and pulmonary function test at present. Analysis of BALF and CT scan findings are useful for the differential diagnosis of BOOP and IPF.