Gaskell B A, Hext P M, Pigott G H, Hodge M C, Tinston D J
Imperial Chemical Industries PLC, Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Toxicology. 1988 Jun;50(1):57-68. doi: 10.1016/0300-483x(88)90121-7.
Rats exposed by inhalation to 3-trifluoromethylpyridine (3-FMP) for 10, 30 or 90 days showed an unusual response in the nasal passages. Focal histological change including reduction in the number of cell layers, disorganisation, vacuolation and minimal necrosis was confined to the olfactory epithelium. Axon bundles and the olfactory bulb were unaffected but there was loss of PAS staining affinity in Bowman's glands. The onset of the lesion showed a very steep dose-relationship approximating a quantal response; no effects were seen after 90 days exposure to 0.1 ppm but the changes were fully developed after 30 days exposure to 0.5 ppm. There was no marked progression with either increased exposure concentrations (up to 329 ppm) or with increased duration of exposure (10-90 days). The respiratory epithelium was generally unaffected apart from a mild irritant response seen only after 90 days. Exposures also resulted in a response in the liver. Centrilobular and midzonal vacuolation was observed at 10 and 30 days following exposures at or above 5 ppm 3-FMP and the severity increased with concentration. The lesion regressed with time even when exposure continued and only minimal changes were evident after 90 days, probably indicating an adaptive response. This work demonstrates the high organ specificity of 3-FMP, particularly for the olfactory epithelium.
通过吸入方式暴露于3-三氟甲基吡啶（3-FMP）10天、30天或90天的大鼠，其鼻腔出现了异常反应。局灶性组织学变化包括细胞层数减少、排列紊乱、空泡化和轻微坏死，局限于嗅觉上皮。轴突束和嗅球未受影响，但鲍曼腺的PAS染色亲和力丧失。病变的发生呈现出非常陡峭的剂量关系，近似于全或无反应；暴露于0.1 ppm 90天后未见影响，但暴露于0.5 ppm 30天后变化完全显现。无论是增加暴露浓度（高达329 ppm）还是增加暴露持续时间（10 - 90天），均未出现明显进展。除仅在90天后出现的轻度刺激反应外，呼吸上皮通常未受影响。暴露还导致肝脏出现反应。在暴露于5 ppm及以上的3-FMP 10天和30天后，观察到小叶中心和中区空泡化，且严重程度随浓度增加。即使继续暴露，病变也会随时间消退，90天后仅出现轻微变化，这可能表明存在适应性反应。这项研究证明了3-FMP具有高度的器官特异性，尤其是对嗅觉上皮。
