Identification of Biomarkers of Chemical Warfare Agents - Report 6: Final report PA-24

Authors:

  • Petrus Hemström
  • Jenny Rattfelt Nyholm
  • Linda Öberg
  • Elisabeth Wigenstam
  • Bo Koch
  • Lina Ågren
  • Sofia Jonasson

Publish date: 2018-11-22

Report number: FOI-R--4638--SE

Pages: 26

Written in: English

Keywords:

  • Biomarkers
  • persistence
  • CWA exposure: rat
  • comparative study: ADD-FOI

Abstract

Project Agreement 24 (PA24) between FOI and the Agency of Defense Development of the Republic of Korea (ADD) aims at examining the persistence of biomarkers verifying exposure to chemical warfare agents. Groups of rats have been exposed to sarin, VX and sulfur mustard at various levels, at different times (1,2,4,7,14,21 and 28 days after exposure), the groups have been terminated and sampled. Plasma from the animals has been divided in three parts, one to ADD and FOI respectively with the third in reserve. The samples have been analyzed using different methods: tyrosine adducts with sarin and VX and fluoride regenerated sarin and the VX regeneration product EMPF. Sulfur mustard has been analyzed as released thiodiglycol (FOI) and as an adduct to albumin, analyzed as a modified tri-peptide (ADD). The results are consistent between ADD and FOI, despite variations in sample preparation methods. The tyrosine adducts with sarin have a life span of about 14 days. It is also the time at which sarin regeneration is possible, probably because the sarin is regenerated from this source. Regeneration of EMPF is possible for only 4 days, 7 at ADD but with extremely low intensity. The difference is likely due to the difference in reactivity leading to the formation of different reaction products by VX and sarin. Sulfur mustard can be detected throughout the sampling period using both methods. However, it is clear that the analysis of albumin adduct (S-HETE-CPY) is clearly preferable, as the method is more stable and there is a risk of exposure to thiodiglycol, which may lead to false positive results. Attempts to identify new biomarkers for exposure to cyanogen chloride have also been conducted. We have conducted in vitro trials where standards, blood and bronchoalveolar lavage fluid have been exposed to cyanogen chloride. We investigated whether the similarities with two other more investigated compounds could provide similar markers. Modified phosphatidylglycerol molecules in the lung have previously been shown as a result of chlorine exposure. We also investigated whether cyanogen chloride may cleave proteins in the same way as cyanogen bromide. Cyanogen bromide is regularly used to cut proteins and gives a very distinctive cleavage pattern. Unfortunately, none of the hypotheses proved true.