Di-n-butyl Phthalate (DNBP) and Diisobutyl Phthalate (DiBP) Metabolism in a Human Volunteer after Single Oral Doses [Journal Article]
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An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dose. For both DnBP and DiBP, the majority of the dose was excreted in the first 24 hours (92.2% of DnBP, 90.3% of DiBP), while only <1% of the dose was excreted in urine on day 2. In each case, the simple monoesters were the major metabolites (MnBP 84% and MiBP 71%). For DnBP, ~7% was excreted as 3OH-MnBP, while 2OH-MnBP, 4OH-MnBP, and MCPP accounted for <1%. For DiBP, close to 20% was excreted as 2OH-MiBP, and <1% as 3OH-MiBP, indicating that the extent of oxidative metabolic modification is around 2.5 times higher for DiBP than for DnBP. All DnBP and DiBP metabolites reached peak concentrations between 2 to 4 hours post-exposure, followed by a monotonic decline. For DnBP metabolites, the elimination half life of MnBP was 3.3 hours; longer half-lives were estimated for the oxidized metabolites (4.5 to 10.3 hours). For DiBP metabolites, MiBP had the shortest half-life (4.2 hours), the oxidized metabolites had somewhat longer half-lives (~4-5 hours). Together with the simple monoesters, secondary oxidized metabolites are additional and valuable biomarkers of phthalate exposure. This study provides basic human metabolism and toxicokinetic data for two phthalates thought to be reproductive toxicants, and that have been shown to be omnipresent in humans.