Total plasma protein adducts of allergenic hexahydrophthalic and methylhexahydrophthalic anhydrides as biomarkers of long-term exposure

Objectives The aim of this study was to evaluate the applicability of total plasma protein adducts (TPPA) of 2 sensitizing low-molecular-weight allerg ens, hexahydrophthalic anhydride (HHPA) and methylhexahydrophthalic anhydri de (MHHPA), as biomarkers of long-term exposure. Methods Urine samples from occupationally exposed workers were analyzed for the levels of urinary metabolites of HHPA and MHHPA, and the levels were u sed as the index of exposure. In addition, blood samples were obtained from the same persons, and the levels of TPPA were determined. Reversed solid p hase extraction, derivatization using pentafluorobenzyl bromide, and gas ch romatography-mass spectrometry analysis in the negative ion chemical ioniza tion mode were used to quantify the exposure. To assess the suitability of TPPA as a biomarker of exposure to the anhydrides, the TPPA levels were cor related to urinary metabolite levels and hemoglobin (Hb) adducts. The toxic okinetics of TPPA were also studied to determine the elimination half-time of the adducts. Results The levels of TPPA correlated exceptionally well with the metabolit e levels in the urine sampled repeatedly, giving r=0.97 for HHPA and r=0.92 for MHHPA. The TPPA of HHPA correlated highly with the Hb adducts with r=0 .86. There were also good correlations between single urinary determination s and the TPPA levels (r(s)=0.71 and 0.81, respectively, for HHPA and MHHPA ). The in vivo decay of TPPA gave an elimination half-time of 22 days for H HPA and 24 days for MHHPA. Conclusions TPPA levels of HHPA and MHHPA are excellent biomarkers of long- term exposure to anhydrides.