Xenobiotic Kinetics and Toxicity among Fish and Mammals
Abstract
Work was focused on paraoxon, a direct inhibitor of acetylcholisterase (AChE) and a potent toxicant on the cholinergic nervous system. While paraoxon inhibits AChE in all tissues, the tissue in which inhibition results in death is not known for certain. It is clear that death after acute paraoxon poisoning results from asphyxiation. The dose of paraoxon at cessation of breath (CoB1) average 5.7 mg/kg at all infusion rates, which suggests that the same site of action and mechanism for paraoxon-induced CoB was in effect at all infusion rates. While heart AChE activity at CoB was independent of the infusion rate, heart appeared not to be the sensitive site since it was pumping blood at CoB. A site of action consistent with the data was CNS outside the blood-brain barrier. With low infusion rate most of the total brain AChE was inhibited. With increasing infusion rate, inhibition of total brain AChE activity would decrease, due to less time for paraoxon to penetrate the BBB; the extra-BBB site would always be rapidly inhibited. Heart and diaphragm AChE was at the level observed at CoB while inhibition of brain AChE increased with increasing dose, again indicating brain as the sensitive site.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 19, 1990
- Accession Number
- ADA229065
Entities
People
- William L. Hayton
Organizations
- Washington State University