Toluene is an organic solvent used in industry and as a substance of abuse. The latter situation may be associated with a leukoencephalopathy characterized by white matter atrophy, multifocal myelin loss, and macrophages that contain birefringent granular inclusions. To determine if rodents can develop the same white matter damage, we studied archived rodent brain samples from three near-lifetime toluene carcinogenicity experiments. Rats and mice were exposed to toluene via an inhalation chamber at 1200 ppm for 6.5 h daily, 5 days per week, for 103 weeks. Rats were exposed to toluene via oral gavage of 800 mg/kg, 4 days per week, for 104 weeks. In gavage-exposed brains, immunohistochemical staining was used to detect reactive astroglial and microglial changes, neuron populations, and cytochrome P450 upregulation. None of the white matter changes reported in human toluene abuse were identified in the rat or mouse brains. In a blinded analysis, a mild widespread increase in reactive microglia was detected in female rats that received toluene by gavage at 800 mg/kg. However, no significant differences were detected in neurons or astrocytes. Potential reasons for the absence of changes are discussed. We conclude that rodent studies designed to study carcinogenicity of toluene might not adequately model abuse exposure.

甲苯是工业上使用的有机溶剂，是一种滥用物质。后一种情况可能与白质脑病有关，白质脑病的特征是白质萎缩，多灶性髓磷脂丢失和含有双折射颗粒状内含物的巨噬细胞。为了确定啮齿动物是否会产生相同的白质损伤，我们研究了来自三个近乎终生的甲苯致癌性实验的啮齿动物大脑样本。大鼠和小鼠通过吸入室在1200 ppm的条件下每天6.5小时，每周5天，每天103周暴露于甲苯中。通过每周800天，每天800天的强饲法将大鼠暴露于甲苯中，持续104周。在强饲法暴露的大脑中，免疫组化染色用于检测反应性星形胶质和小胶质细胞变化，神经元种群和细胞色素P450上调。在大鼠或小鼠的大脑中，没有发现人类滥用甲苯中报道的白质变化。在盲法分析中，在以800 mg / kg的管饲法接受甲苯的雌性大鼠中，检测到反应性小胶质细胞轻度普遍增加。但是，在神经元或星形胶质细胞中未检测到显着差异。讨论了没有更改的潜在原因。我们得出的结论是，旨在研究甲苯致癌性的啮齿动物研究可能不足以对滥用行为进行建模。讨论了没有更改的潜在原因。我们得出的结论是，旨在研究甲苯致癌性的啮齿动物研究可能不足以对滥用行为进行建模。讨论了没有更改的潜在原因。我们得出的结论是，旨在研究甲苯致癌性的啮齿动物研究可能不足以对滥用行为进行建模。