Histopathology of acute toxic responses in selected tissues from rats exposed by inhalation to methyl bromide.

To determine and characterize the histological changes induced in selected tissues from the Fischer 344 rat by acute inhalation exposure to methyl bromide (MeBr), groups of 10 male rats (11-13 weeks old) were exposed to 0, 90, 175, 250, or 325 ppm MeBr 6 hr/day for 5 days. Animals were anesthetized with phenobarbital then perfusion-fixed 1-2 hr after the last exposure or in extremis (325 ppm, 4 days) with Karnovsky's fixative and selected tissues were processed for light microscopy. With the exception of the nasal passages, tissues were selected on the basis of previous studies with methyl chloride (MeCl). The nose was examined as part of ongoing research of nasal toxicity in this laboratory. The principal clinical signs, confined to the 250 and 325 ppm groups, were diarrhea, hemoglobinuria, and, in a few cases, gait disturbances and convulsions. A dose-dependent vacuolar degeneration of the zona fasciculata of the adrenal glands, cerebellar granule cell degeneration, and nasal olfactory sensory cell degeneration were seen in all concentration groups except at 90 ppm. Cerebral cortical degeneration and minor alterations in testicular histology were seen only in the 325 ppm group. Hepatocellular degeneration was confined to the 250 and 325 ppm groups. No changes were seen in the kidneys or epididymides. This study demonstrates that MeBr has similar target organs to MeCl suggesting that similar mechanisms of toxicity may be operational. However, important differences in the nature of cellular responses to these chemicals may facilitate studies on their mechanisms of actions.