In vivo 31P nuclear magnetic resonance studies on the absorption of triphenyl phosphite and tri-o-cresyl phosphate following subcutaneous administration in hens.
Carrington-CD; Burt-CT; Abou-Donia-MB
Drug Metab Dispos 1988 Jan; 16(1):104-109
The rates of disappearance of triphenyl-phosphite (101020) (TPP), 1000mg/kg, and tri-o-cresyl-phosphate (78308) (TOCP), 1187mg/kg, were monitored following subcutaneous injection in adult white- Leghorn-hens to determine the extent to which slow absorption could account for the prolonged neuropathy-target-enzyme inhibition noted in earlier studies of subcutaneous injection of these compounds. In- vivo phosphorus-31 nuclear magnetic resonance (NMR) was used to monitor the compounds. Because the animals began to die in the third week following injection, measurements could not be extended further than about one half life. Absorption of either compound was very slow. In experiments with a large phosphorus tuned copper coil placed to more than cover the injection site, the amount of either compound detected by the NMR coil diminished in two phases. A rapid phase occurred over a period of a few hours, while a slower phase occurred over several weeks. Two findings suggested that the rapid phase resulted from spread of some material underneath the skin so that it was beyond the range of the coil. Moving the coil slightly away from the injection site produced a signal with magnitude close to the initial signal. Also, more rapid loss of signal occurred when a smaller coil was used. During the slow phase, which apparently corresponded to absorption, both compounds disappeared slowly with a half life of about 2 weeks. In two animals given subcutaneous doses of TPP, a different absorption pattern was noted. In these hens, TPP converted to diphenyl-phosphonic-acid within hours following injection. Both died of acute toxicity after 4 and 6 hours. Conversion to diphenyl-phosphonic-acid also occurred in in- vitro experiments. The authors conclude that TOCP and TPP are absorbed very slowly when injected subcutaneously, which could account for delayed neuropathy, and that diphenyl-phosphonic-acid may be important in toxicity of TPP.
NIOSH-Publication; NIOSH-Grant; Neurotoxic-effects; Organo-phosphorus-compounds; Laboratory-animals; Neurotoxicity; Metabolic-study; Absorption-rates; Tissue-distribution; Nervous-system
Pharmacology Duke University Department of Pharmacology Durham, N C 27710
Neurotoxic Disorders; Neurotoxic-effects
Drug Metabolism and Disposition
Duke University, Durham, North Carolina