SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

C23
BIOMONITORING OF EXPOSURE TO CHEMICAL WARFARE AGENTS
D. Noort*, MJ. van der Schans and H.P. Benschop
Division of Chemical & Biological Protection, TNO Prins Maurits Laboratory, P.O. Box 45, 2280 AA
Rijswijk,The Netherlands
Methods to analyze chemical warfare agents (CWA) and their decomposition products in environmental
samples were developed over the last decades. On the other hand, methods for such analyses in biological
samples have only recently become available. Retrospective detection of exposure to CW A can be useful
for various applications. With regard to the "Homeland Defense" program, it can be envisaged that rapid
diagnostic methods can play a pivotal role in case of a terrorist attack with CWA. In the same context,
confirmation of non-exposure of worried citizens is of utmost importance. Also, such methods can be used
for forensic analyses in case of suspected terrorist activities ("chemical fingerprints"). It is self-evident that
these methods will also be highly valuable from a military point of view, e.g., to establish firmly to which
chemicals casualties have been exposed to, which is a starting point for adequate medical treatment, or for
health surveillance of workers in destruction facilities of chemical warfare agents. This presentation will
focus on a number of specific methods currently available for verification of exposure to the most common
CWA, i.e., nerve agents and mustard agents.
There are basically four methods to diagnose an exposure to a nerve agent:
1. cholinesterase inhibition measurements
2. analysis ofhydrolysis products, e.g., alkyl methylphosphonic acids
3. analysis of generated phosphofluoridates after treatment of blood with fluoride ions ("fluoride
reactivation")
4. mass spectrometric analysis of phosphylated peptides after enzymatic digestion of modified
cholinesterase.
For mustards, there are three distinct methods to assess an exposure:
1. mass spectrometric analysis of low molecular urinary metabolites
2. analysis of DNA adducts by means of mass spectrometric or immunochemical methods.
3. mass spectrometric analysis of protein adducts, e.g., to hemoglobin and albumin.
This presentation will focus on methods that are based on the analysis oflong-Iived protein adducts, i.e., on
methods 3 and 4 for nerve agents and on method 3 for mustards. Advantageously, protein adducts are stable
and therefore detectable weeks or even months after the exposure, in contrast to DNA adducts and urinary
metabolites which are excreted much more rapidly. The developed technology will be described briefly and
examples of real exposure incidents will be presented.
Acknowledgements: This presentation covers work that was funded by the US Army Medical Research and
Materiel Command, by the Bundesministerium der Verteidigung, InSan I 3, Germany, and by the
Directorate of Military Medical Service ofthe Ministry ofDefense, The Netherlands.
Keywords: chemical warfare agents, adducts, diagnosis
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