Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses.

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 h post-dose. For both DnBP and DiBP, the majority of the dose was excreted in the first 24 h (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 %; MiBP, 71 %). For DnBP, ~8 % was excreted as various side chain oxidized metabolites. For DiBP, approximately 20 % was excreted mainly as the oxidized side chain metabolite 2OH-MiBP, indicating that the extent of oxidative modification is around 2.5 times higher for DiBP than for DnBP. All DnBP and DiBP metabolites reached peak concentrations between 2 and 4 h post-exposure, followed by a monotonic decline. For DnBP metabolites, the elimination halftime of MnBP was 2.6 h; longer elimination halftimes were estimated for the oxidized metabolites (2.9-6.9 h). For DiBP metabolites, MiBP had the shortest halftime (3.9 h), and the oxidized metabolites had somewhat longer halftimes (4.1 and 4.2 h). 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 that have to be considered human reproductive toxicants and that have been shown to be omnipresent in humans.

The contribution of diet to total bisphenol A body burden in humans: results of a 48 hour fasting study.

Human biomonitoring studies measuring bisphenol A (BPA) in urine have shown widespread exposure in the general population. Diet is thought to be a major route of exposure. We studied urinary BPA patterns in five individuals over a 48-h period of fasting (bottled water only). Personal activity patterns were recorded with a diary to investigate non-dietary routes of exposure. All urine void events during the fast were collected, as well as events before and after the fast. The pattern of BPA concentrations was similar for all participants: they rose near the beginning of the fast (after the pre-fast meal), declined over the next 24h, fluctuated at lower levels during the second day, and then rose after the post-fast meal. Concentrations (~2 µg/g creatine) and calculated BPA intakes (~0.03 µg/kg-day) in these individuals during the first 24h were consistent with general population exposures. For the second 24h, concentrations and intakes declined by about two-thirds. One of the individuals had an extraordinary pre-fast exposure event with concentrations rising as high as 98 µg/g creatine but declining to <5 µg/g creatine by day 2. Given patterns found in day 1 and the subsequent decline to lower levels in day 2, we hypothesize that BPA exposures in these individuals were diet-driven. No events in the diary (use of personal care products, e.g.) appear associated with exposures. On day 2, non-dietary sources may still be present, such as from dust. Another hypothesis is that small reservoirs of BPA from past exposures are released from storage (lipid reservoirs, e.g.) and excreted.