Abstract
Introduction
Recent malicious use of chemical warfare agents (CWAs) is a reminder of their severity and ongoing threat. One of the main categories of CWAs is the organophosphate (OP) nerve agents. Presently, there is an urgent need to identify and evaluate OP nerve agent biomarkers that can facilitate identification of exposed individuals post-CWA incident. While exposures to OP nerve agents may be scenario-specific, the public is commonly exposed to OP compounds through the ubiquitous use of OP pesticides, which are chemically related to nerve agents. Therefore, a systematic literature review and methodological quality assessment were conducted for OP pesticide biomarker studies to serve as a baseline to assess if these approaches may be adapted to OP nerve agent exposures.
Materials and Methods
We conducted a systematic literature review to identify biomarkers of OP pesticide exposures. English language studies of any design that reported primary data on biomarkers for exposures in nonhuman primates or adult human study participants were eligible for inclusion. Using standard criteria for assessing the completeness of reported analytical methods, the quality of study methods was critically evaluated.
Results
A total of 1,044 studies of biomarkers of OP pesticide exposure were identified, of which 75 articles satisfied the inclusion and exclusion criteria. These studies described 143 different analyte/sample matrix combinations: 99 host-based biomarkers, 28 metabolites, 12 pesticides, and 4 adducts. The most commonly reported biomarkers were dialkyl phosphate urinary metabolites (22 studies), blood acetylcholinesterase, and plasma butyrylcholinesterase (26 studies each). None of the assessed quality review criteria were fully addressed by all identified studies, with almost all criteria scoring less than 50%.
Conclusion
Cholinesterase activity may have utility for identifying individuals with exposures surpassing a given threshold of OP nerve agent, but further investigation of how acetylcholinesterase and butyrylcholinesterase levels correlate with observed patient symptoms may be required to ensure accuracy of results. As CWAs and nerve agents are more readily used, more standardized reporting of biomarker measurements are needed to develop new approaches for OP nerve agent biomarkers.
Backbone Conformation Shifts in X-ray Structures of Human Acetylcholinesterase upon Covalent Organophosphate Inhibition
