Retrospective detection of exposure to organophosphates: analysis in blood of human beings and rhesus monkeys
bookPart
The terrorist attacks with nerve agents in Japan as well as the ongoing debate on a possible relationship between the so-called Gulf War Syndrome and accidental exposure to traces of nerve agents have made clear that improved methods for detection of exposure to organophosphates are needed. Low level exposures can not be detected by the methods which, are presently available. In addition, these methods have a limited value for retrospective analysis. We developed a method for biomonitoring of human exposure based on organophosphate-inhibited butyrylcholinesterase (BuChE) as the most persistant and abundantly available marker in blood. High concentrations of fluoride ions release the organophosphate from BuChE with formation of a phosphofluoridate, which is specific for the organophosphate used except for its leaving group. The phosphofluoridate can be identified and quantitated, e.g., by means of gas chromatography, in order to determine origin and extent of poisoning. In the present work we studied during which period of time the new method can be used subsequent to sublethal exposure to tabun or sarin (1–4 μg/kg, i.v.) of atropinized rhesus monkeys, as a model for humans. It appeared that exposure could be monitored in these animals for 3–5 weeks at inhibition levels of BuChE ≥ 0.01%. In addition, a method was developed for LC-MS-MS analysis of the hydrolysis product of sarin in blood. The usefulness of the new procedures was demonstrated by our preliminary analysis of serum samples from victims of the terrorist attack in the Tokyo subway and in Matsumoto.
TNO Identifier
131123
ISBN
978-0-7923-5803-9
Publisher
Kluwer Academic Publishers
Source title
NBC Risks Current Capabilities and Future Perspectives for Protection (Kluwer)
Editor(s)
Sohns, T.
Voicu, V.A.
Voicu, V.A.
Pages
513-521
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