Prolonged exposure to trimethylphosphate induces sensory motor neuropathy in the dog

Five beagle dogs were treated daily with 1 ml of trimethylphosphate (TMP) for 1 to 4 months. Neurotoxicity was evaluated by observation of behaviour, neurologic examination, neurophysiologic tests and by neuropathology. Neurotoxicity was first detected at the neurologic examination following four weeks of treatment: the most predictive indicators of neuropathy were the impairment of hopping, of tactile placing and the atactic gait. Electrophysiologic tests indicated a prolonged latency of neuromuscular impulse transmission after week nine, followed by a decrease of maximum conduction velocity of sensory fibers. At this time peripheral nerve fibers had abnormalities including paranodal and internodal swelling, paranodal demyelination and distal fragmentation. An additional dog treated with daily doses of 2 ml developed a severe distally accentuated degeneration of long spinal tracts and peripheral nerve fibers, manifested by impairment of sensory and central motor impulse conduction. Organophosphate neuropathy can thus be assessed in the dog by functional and morphological changes after prolonged exposure, in particular at doses causing severe morbidity.