Histopathological assessment of triphenyl phosphite neurotoxicity in the hen.
Carrington-CD; Brown-HR; Abou-Donia-MB
Neurotoxicology 1988 Mar; 9(2):223-234
The clinical and histopathological effects of triphenyl-phosphite (115866) (TPP) were examined in a dose and time dependent manner. A comparison was also made of the neurotoxicity of TPP to the effects of diisopropyl-phosphorofluoridate (55914) (DFP) and tri-o-cresyl- phosphate (78308) (TOCP). The ability of phenylmethylsulfonyl- fluoride (PMSF) to prevent the neuropathies induced by subcutaneous doses of either TPP or TOCP was studied and the ability of DFP to cause additional damage after exposure to TPP was investigated. White-leghorn-hens were treated with TPP doses of 250, 500, or 1000mg/kg and evaluation for pathological changes was conducted 21 days later. In the comparison studies, TOCP was administered at a dose of 1187mg/kg and DFP at 1.7mg/kg. All three chemicals were administered subcutaneously in the neck. Progressive ataxia and paralysis developed 5 to 10 days after dosing with TPP at 1000mg/kg. Axonal damage in the lateral columns of the spinal cord and peripheral nerve accompanied the clinical signs. Similar signs followed neurotoxic doses of TOCP or DFP. TPP caused damage to axons in the brain and gray matter of the spinal cord with chromatolysis and neuronal necrosis observed in the spinal cord; these effects were not observed following treatment with TOCP or DFP. All histopathologic changes observed with TPP were dose dependent. The minimum neurotoxic dose of TPP was 500mg/kg. The incidence of damage to the peripheral nerve of TPP treated animals was reduced by prior administration of 30mg/kg PMSF. However, PMSF did not prevent toxicity to the cell bodies in the spinal cord or the clinical effects. The authors conclude that TPP caused neuronal damage in addition to the axonal damage associated with organophosphorous compound induced delayed neuropathy, and suggest that two distinct mechanisms underlie the neurotoxicity of TPP.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Agricultural-chemicals; Organo-phosphorus-compounds; Organo-phosphorus-pesticides; Histopathology; Cell-damage; Nerve-tissue; Nervous-system-disorders
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
115-86-6; 55-91-4; 78-30-8
Neurotoxic Disorders; Neurotoxic-effects
Duke University, Durham, North Carolina