Determination of total and free mono-n-butyl phthalate in human urine samples after medication of a di-n-butyl phthalate containing capsule

Phthalates like di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) are commonly used as plasticisers, enteric coatings in medications and their metabolites (MnBP respectively MiBP) are suspect of adverse endocrine activities. The aim of this study was to determine kinetical data in humans after the application of a drug containing 3600 μg of DnBP and to quantify main metabolites of DnBP and DiBP with and without glucuronidase treatment. Since commonly glucuronides do not exhibit endocrine activity it is of interest to determine the potentially active metabolite like free MnBP and MiBP for a valid risk assessment. After the application of one capsule containing 3600 μg of DnBP to 17 volunteers 78% (median of 2248 μg of total MnBP) of administered DnBP was found within 24 h in urine. After 24 h the levels of MnBP in urine were comparable to concentrations before administration showing a fast elimination. In contrast to controls in all urine samples collected within 24 h after the administration of the drug free MnBP was observed with a median of 4% of total MnBP. In controls total MnBP and MiBP were found in median concentration of 23 μg/24 h and about 50 μg/24 h, respectively and therefore environmental exposure to DnBP is only 1% compared to medication. Since an uptake of 3600 μg in only one capsule is already above the tolerable daily intake (TDI) for DnBP of 10 μg/kg b.w. from a preventive health protection DnBP should be replaced in medical drugs.