A biomarker approach to measuring human dietary exposure to certain phthalate diesters

Abstract

Three groups of eight volunteers were administered stable isotope-labelled phthalate diesters in a single dose and the amount of the corresponding phthalate monoesters excreted in the urine was measured. Amongst the phthalates administered were the symmetrical dibutyl-, di-2-ethyl- and diisooctyl- phthalates along with the unsymmetrical benzylbutylphthalate. The control group received no dose, the low dose group received 168-255 microg of each phthalate and the high dose group received 336 to 510 microg of each phthalate. The excreted phthalate monoesters were measured by LC-MS following hydrolysis of conjugates. The bulk of phthalate monoester was excreted in the first 24 hour period following the dose. For dibutylphthalate, 64% and 73% on a mole basis of the low, and high dose respectively was excreted as monobutylphthalate. For dioctylphthalate (sum of the 2-ethylhexyl and the isooctyl species) the yield was 14 and 12% of the low and high dose excreted as monooctylphthalate. For benzylbutylphthalate, 67% and 78% was eliminated as monobenzylphthalate and only 6% (measured for the high dose only) was eliminated as monobutylphthalate. These conversion factors can be used in future studies to assess exposure to phthalate esters via measuring urinary levels of the monoester metabolites.

Estimated daily intake of phthalates in occupationally exposed groups

“…Nonetheless, with 9-25 workers per sector, some of this temporal variability was likely averaged across workers. Temporal variability in metabolite concentrations is further heightened by the metabolites' relatively short half-lives and rapid elimination in the urine (Anderson et al, 2001;Api, 2001;Koch et al, 2005aKoch et al, , 2004. Within-person variability in urinary phthalate metabolite concentrations has been shown to depend on the population, phthalate metabolite, and time frame of interest (Hoppin et al, 2002;Hauser et al, 2004;Fromme et al, 2007;Teitelbaum et al, 2008).…”

“…F UE values for MBP (0.69) and monobenzyl phthalate (MBzP, 0.73) were taken from published human data (Anderson et al, 2001). F UE values for MEP and monoisobutyl phthalate (MiBP) were set to that of MBP (Kohn et al, 2000;Koch et al, 2003b).…”

“…We estimated BzBP and DiBP daily intake using their respective monoesters only. Only 6% of ingested BzBP is excreted as MBP (Anderson et al, 2001); therefore, MBzP was considered the principal BzBP metabolite.…”

Exposure assessment of phthalate esters in Japanese pregnant women by using urinary metabolite analysis

“…F UE is the molar fraction of the urinary-excreted monoester related to the parent diesters. F UE values were as follows: for MnBP, 0.69 was used based on report of Anderson et al [23]. F UE for MMP and MEP were unknown and substituted with that for MnBP.…”

Plasticizer concentration in cord blood cryopreserved with DMSO

“…In general, children showed higher concentrations of DEHP metabolites than adults with higher ratios of the oxidative metabolites compared to MEHP (Becker et al 2004, CDC 2005, Koch et al 2004a). From the urinary concentrations measured daily DEHP exposure has been calculated by comparison with urinary excretion rates determined in human metabolism studies (Anderson et al 2001, Koch et al 2004b, Koch 2005a, Schmid ans Slatter 1985. Since in the most metabolite excretion studies 24h urine samples were not available the amount of the DEHP metabolites excreted throughout a day has to be extrapolated from spot urine concentrations.…”