Reuhl K R, Gilbert S G, Mackenzie B A, Mallett J E, Rice D C
Toxicol Appl Pharmacol. 1985 Jul;79(3):436-52. doi: 10.1016/0041-008x(85)90141-3.
Adult cynomolgus monkeys were administered trimethyltin (TMT) iv in dosages ranging from 0.75 to 4.0 mg TMT/kg and observed for behavioral changes. Animals were subsequently killed for light and electron microscopic examination. TMT showed a dose-related toxicity, with high dose animals (4.0 and 3.0 mg/kg) dying within 24 hr, and low dose animals (0.75 mg/kg) surviving without morphological effects. Animals given 1.10 mg TMT/kg displayed a reproducible clinical course, characterized by tremor, hyperactivity, and ataxia which progressed to stupor and finally unconsciousness. By light microscopy, neuropathology was most pronounced in the CA-3 and CA-4 regions of Ammon's horn. Degenerating pyramidal neurons, micro- and astrogliosis, and neuronophagia were commonly observed. Mild degenerative changes were identified in amygdala, medulla, spinal cord, and Purkinje cells. The fascia dentata remained intact. Ultrastructurally, injured neurons contained accumulations of lysosomes and lysosome-like structures within perikarya and neurites. Demyelination or vascular damage was not observed. Data indicate the monkey to be highly sensitive to TMT, with morphological injury most severe in limbic structures.
成年食蟹猴通过静脉注射三甲基锡（TMT），剂量范围为0.75至4.0毫克TMT/千克，并观察其行为变化。随后处死动物进行光镜和电镜检查。TMT显示出剂量相关的毒性，高剂量组动物（4.0和3.0毫克/千克）在24小时内死亡，低剂量组动物（0.75毫克/千克）存活且无形态学影响。给予1.10毫克TMT/千克的动物表现出可重复的临床病程，其特征为震颤、多动和共济失调，随后发展为昏迷并最终失去意识。光镜下，神经病理学改变在海马角的CA-3和CA-4区域最为明显。常见到锥体神经元退变、小胶质细胞和星形胶质细胞增生以及噬神经元现象。在杏仁核、延髓、脊髓和浦肯野细胞中发现了轻度退行性改变。齿状回保持完整。超微结构上，受损神经元在胞体和神经突内含有溶酶体和类溶酶体结构的聚集物。未观察到脱髓鞘或血管损伤。数据表明食蟹猴对TMT高度敏感，边缘结构的形态学损伤最为严重。
