Acute trimethyltin intoxication in the monkey (Macaca fascicularis)

Area of Science:

• Neuroscience
• Toxicology
• Primate Research

Background:

• Trimethyltin (TMT) is a neurotoxicant known to affect the central nervous system.
• Understanding TMT's specific effects and target regions is crucial for assessing its toxicological profile.

Purpose of the Study:

• To investigate the dose-dependent behavioral and neuropathological effects of trimethyltin (TMT) in adult cynomolgus monkeys.
• To identify the specific brain structures most vulnerable to TMT-induced toxicity.

Main Methods:

• Adult cynomolgus monkeys received intravenous administration of TMT at varying doses (0.75 to 4.0 mg/kg).
• Behavioral changes were systematically observed and recorded.
• Post-mortem examination included light and electron microscopy of brain tissue.

Main Results:

• TMT exhibited dose-related toxicity, with higher doses causing mortality within 24 hours.
• A reproducible clinical syndrome (tremor, hyperactivity, ataxia, stupor, unconsciousness) was observed at 1.10 mg TMT/kg.
• Neuropathology, including neuronal degeneration and neuronophagia, was most severe in the CA-3 and CA-4 regions of the hippocampus (Ammon's horn).
• Mild degenerative changes were noted in the amygdala, medulla, spinal cord, and Purkinje cells, while the fascia dentata remained unaffected.
• Ultrastructural analysis revealed lysosomal accumulation in injured neurons, with no observed demyelination or vascular damage.

Conclusions:

• Cynomolgus monkeys are highly sensitive to trimethyltin (TMT).
• Limbic structures, particularly the hippocampus, are the primary targets of TMT-induced morphological injury.
• The observed effects provide a detailed neurotoxicological profile of TMT in a primate model.