Quantification of Trisaminohexyl Isocyanurate (TAHI) as a Biomarker of HDI Isocyanurate Exposure in the Plasma and Urine of Automotive Spray Painters

摘要

Biological monitoring of occupational exposure to 1,6-hexamethylene diisocyanate (HDI)-containing spray-paints is limited to analysis of metabolites of HDI monomer although polymeric HDI isocyanurate constitutes the predominant inhalation and skin exposures for workers in the automotive paint industry. In order to investigate HDI isocyanurate and HDI monomer exposure-biomarker associations, we developed a novel method to quantify trisaminohexyl isocyanurate (TAHI) as a biomarker of HDI isocyanurate exposure in biological samples collected from occupational^ exposed spray-painters. Plasma and urine samples were acid hydrolyzed, extracted with dichloromethane, and derivatized with acetic anhydride prior to analysis of the derivatized product, trisacetamidohexyl isocyanurate (TAAHI), with nanoflow ultra-performance liquid chromatography coupled to nano-electrospray ionization tandem mass spectrometry (nano-UPLC-ESI-MS/MS). Analytical and internal standards required for analysis were not available commercially and, subsequently, were synthesized in-house. The calibration curves and method detection limits (MDL) were sensitive and specific for spiked control plasma (N = 11; 0.03 - 3.99 ug/L; r = 1.000; MDL = 0.02 ug/L) and spiked control urine (N = 13; 0.06 - 7.98 ug/L; r = 0.998; MDL = 0.03 ug/L). TAHI was detected in 23 of 112 plasma samples (13 of 46 workers) with an arithmetic mean ± standard deviation of 0.014 ± 0.042 ug/L, and in 130 of 417 urines samples (36 of 48 workers) with an arithmetic mean ± standard deviation of 0.204 ± 0.705 ug/L. The quantification of TAHI as a biomarker of HDI isocyanurate exposure is essential for future research on the pharmacokinetics of uptake and elimination in order to determine the relative potency and dose-relationships between HDI monomer and oligomer exposure.