Organophosphate esters and their metabolites in paired human whole blood, serum, and urine as biomarkers of exposure

Although organophosphate diester (di-OPE) metabolites in urine are usually used to assess human exposure to organophosphate esters (OPEs), whether they can reflect human exposure to all OPEs with great differences in chemical structures and properties is still currently unclear. In this study, we detected sixteen OPEs and ten di-OPEs in 52 paired whole blood, serum, and urine samples collected in Beijing, China to investigate the correlations between different compounds and matrices, thus providing proper biomarkers of human exposure to OPEs. The order of the median concentrations of ∑OPEs was whole blood (8.63 ng/mL) > serum (5.71 ng/mL) > urine (0.396 ng/mL), while those of ∑di-OPEs followed the order of urine (16.6 ng/mL) > whole blood (5.97 ng/mL) > serum (3.70 ng/mL). Ethylhexyl diphenyl phosphate (EHDPP) and cresyl diphenyl phosphate (CDPP) were the dominant OPEs in both whole blood and serum samples and were significantly correlated between these two matrices. The distribution of OPEs in human blood was evaluated according to serum-to-whole blood concentration ratios (S:WB ratios). The median S:WB ratios of triethyl phosphate (TEP), tri-n-butyl phosphate (TnBP), bisphenol-A bis(diphenyl phosphate) (BABP), EHDPP, and CDPP were lower than 1, indicating that these OPEs preferred to accumulated in blood cells rather than in serum/plasma. Bis(2-ethylhexyl) phosphate (BEHP) was the major di-OPEs and was detected in almost all whole blood, serum and urine samples. The median whole blood: urine (WB:UR) ratios of di-OPEs were significantly and positively correlated with their logKow values, indicating that di-OPEs with low hydrophobicity were prone to excretion via urine. Based on the relationships between OPEs and di-OPEs in these matrices, the parent OPEs in whole blood can be recommended for use as alternative biomarkers of aryl-OPEs exposure in future human biomonitoring studies, in addition to metabolites in urine.