Phosgene protein adducts

Blood Protein adduct Albumin peptide LC-MS-MS Whole blood treated with known phosgene concentrations Specific and sensitive LOD luM Standards not easily available... 

As described below, urinary metabolites have been identified for vesicants, nerve agents, 3-quinuclidinyl benzilate (BZ), hydrogen cyanide and the RCAs, CS, CR and capsaicin. Protein adducts have been identified for vesicants, nerve agents and phosgene, and DNA adducts for sulphur and nitrogen mustards. With the rapid advances being made in proteomics and metabo-nomics, new biological markers of exposure will undoubtedly be identified in the near future. 

Vesicants, nerve agents, and phosgene are reactive electrophiles that react covalently with nucleophilic sites on macro molecules. Reactive nucleophilic sites exist on the bases and phosphate groups of DNA molecules. An advantage of DNA as a substrate is that it is present in all tissues of the body. A disadvantage is that repair mechanisms tend to excise the alkylated moiety, resulting in a much shorter lifetime compared to alkylated proteins (for a recent review of mass spectrometry for quantitation of DNA adducts, see Koc and Swen-berg <2>). 

Figure 7.29 Chloroform is also metabolized by oxidative dehalogenation to form the toxic compound phosgene. While this can react with water to form carbonic acid that breaks down into carbon dioxide and water it can also react with nucleophilic groups in proteins and nucieic acids. If it reacts twice, the result is a cross-linked adduct which is very difficult for the body to repair.

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