CHRONIC RETICULOENDOTHELIAL CELL STORAGE DISEASE.
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Biomedical subjects
Publications and source records attributed to P HOLLAND.
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Using the thiocholine method, a restricted survey has been made of cholinesterases in the spinal cord and brain stem of the chicken. No simple relation between sites of selective damage in organophosphorus neurotoxicity and centres of cholinesterase activity could be adduced. Moreover, no significant differences between species susceptible and insusceptible to poisoning by these compounds were found by this method. It is concluded that, while cholinesterase may well play an intermediary role in the intoxication, other factors determine the selective damage to certain neurones and their processes.
Tri-p-ethylphenyl phosphate is unique amongst the organophosphorus compounds which produce neurotoxic effects in not being an inhibitor of cholinesterase. The dysfunction it produces is also marked by some unusual features. Thus it produces a characteristic high-stepping gait which develops at varying periods after intramuscular injection but more regularly following oral administration. A careful comparison of the character, onset and development of the effects of diisopropyl phosphorofluoridate (dyflos), tri-o-cresyl phosphate and tri-p-ethylphenyl phosphate has illustrated the differences between the two former substances and tri-p-ethylphenyl phosphate. It has also confirmed a previous suggestion that this substance acts in a different manner from the other two, a suggestion supported by the histological evidence.
Thirty-six alkyl organophosphorus compounds have been tested for neurotoxicity in the chicken. The individual compounds were chosen to enable the importance of each portion of the molecule to be assessed in relation to the property of neurotoxicity. Seventeen substances were found to be neurotoxic, fifteen for the first time. All of these contained fluorine. On the basis of the results reported, certain predictions have been made about the chemical structure of compounds which would be expected to be neurotoxic. The importance of fluorine suggests that it plays a direct role in the development of the biochemical lesion, and this may occur as the result of its being carried by the molecule as a whole to specific areas in the nervous system. By the action of cholinesterase, the P-F bond may be ruptured and ionic fluorine liberated where it blocks some metabolic cycle.