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Histopathology of acute toxic responses in selected tissues from rats exposed by inhalation to methyl bromide
M E Hurtt1, K T Morgan, P K Working
1Department of Genetic Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Abstract:
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.
Insights
Acute inhalation of methyl bromide (MeBr) in Fischer 344 rats caused dose-dependent histological changes in adrenal glands, cerebellum, and nasal passages. Methyl bromide shares target organs with methyl chloride, suggesting similar toxicity mechanisms.
Area of Science:
- Toxicology
- Histopathology
- Inhalation Exposure
Background:
- Methyl bromide (MeBr) is a fumigant with known toxicity.
- Previous studies indicate methyl chloride (MeCl) affects similar organs.
- Understanding MeBr's specific histological effects is crucial for risk assessment.
Purpose of the Study:
- To characterize histological changes in Fischer 344 rats after acute methyl bromide inhalation.
- To compare the target organs of MeBr with those of MeCl.
Main Methods:
- Male Fischer 344 rats were exposed to varying concentrations of MeBr (0-325 ppm) for 6 hours/day over 5 days.
- Tissues were collected via perfusion fixation and examined using light microscopy.
- Clinical signs and dose-dependent histological alterations were documented.
Main Results:
- Dose-dependent vacuolar degeneration observed in adrenal zona fasciculata, cerebellar granule cells, and nasal olfactory sensory cells (except at 90 ppm).
- Hepatocellular degeneration occurred at 250 and 325 ppm.
- Cerebral cortical degeneration and minor testicular changes were noted only at 325 ppm; no kidney or epididymis changes were observed.
Conclusions:
- Methyl bromide induces significant, dose-dependent histological damage in specific rat tissues, including the adrenal glands, cerebellum, and nasal passages.
- The observed target organs overlap with those affected by methyl chloride, suggesting potential similarities in toxicological mechanisms.
- Differences in cellular responses may offer avenues for further research into the mechanisms of action for both MeBr and MeCl.