Toxicokinetic of tris(2-butoxyethyl) phosphate (TBOEP) in humans following single oral administration

Tris(2-butoxyethyl) phosphate (TBOEP; 20 mu g/kg b.w.) was orally administered to three female and three male volunteers. In urine samples collected for 39 h three metabolites of TBOEP were quantitated. bis(2-butoxyethyl) phosphate (BBOEP), tris(2-(3-hydroxy)butoxyethyl) phosphate (OH-TBOEP), bis(2-butoxyethyl)-(2-hydroxyethyl) phosphate (BBOEHEP) were observed in all urine samples within the first 7 h with highest concentration for BBOEHEP. C-max of OH-TBOEP was in the range of 2-4 h and t(1/2) was between 1.5 and 6.1 h. Similar results were obtained for BBOEHEP. In contrast BBOEP showed several maxima within 25 h and, therefore, no toxicokinetic data were calculated. As proof of concept 54 urine samples of children staying at day-care centers in Germany were analysed for all 3 biomarkers. Only BBOEP and BBOEHEP were detected in about 80% of the samples with a median of 0.16 mu g/l for BBOEP and 0.18 mu g/l for BBOEHEP. A recalculation of daily intake (DI) based on BBOEHEP resulted in a clear undercut of the current reference dose of 50 mu g/kg per day. As observed in other studies a calculation of the DI based on the dust concentrations and oral uptake of 20 mg of dust for 8 h for young children results in considerably higher DI but would also not exceed the RfD.