Hurtt M E, Morgan K T, Working P K
Department of Genetic Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709.
Fundam Appl Toxicol. 1987 Aug;9(2):352-65. doi: 10.1016/0272-0590(87)90057-1.
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.
为了确定并描述急性吸入溴甲烷（MeBr）对Fischer 344大鼠选定组织诱导产生的组织学变化，将10只雄性大鼠（11 - 13周龄）分为几组，每天6小时、连续5天暴露于0、90、175、250或325 ppm的MeBr环境中。动物用苯巴比妥麻醉，在最后一次暴露后1 - 2小时或濒死时（325 ppm，4天）用卡诺夫斯基固定液进行灌注固定，然后对选定组织进行光学显微镜检查。除鼻道外，其他组织的选择基于先前对氯甲烷（MeCl）的研究。作为本实验室正在进行的鼻毒性研究的一部分，对鼻子进行了检查。主要临床症状仅限于250 ppm和325 ppm组，表现为腹泻、血红蛋白尿，少数情况下出现步态障碍和惊厥。除90 ppm组外，在所有浓度组均观察到肾上腺束状带剂量依赖性空泡变性、小脑颗粒细胞变性和鼻嗅觉感觉细胞变性。仅在325 ppm组观察到大脑皮质变性和睾丸组织学的轻微改变。肝细胞变性仅限于250 ppm和325 ppm组。肾脏和附睾未见变化。本研究表明，MeBr与MeCl具有相似的靶器官，提示可能存在相似的毒性作用机制。然而，这些化学物质在细胞反应性质上的重要差异可能有助于对其作用机制的研究。
