Occurrence and daily variation of phthalate metabolites in the urine of an adult population.

Phthalates like di-(2-ethylhexyl) phthalate (DEHP) are commonly used as plasticizers and their metabolites are suspect of especially reproductive toxicity. The aim of our study was to assess phthalate exposure in adults by measuring urinary phthalate metabolite levels and to explore individual temporal variability. Urine samples were collected by 27 women and 23 men aged 14-60 years during 8 consecutive days. We quantified four monoesters, four oxidative DEHP metabolites, and two secondary metabolites of di-isononyl phthalate (DiNP) by a LC/LC-MS/MS method. If we analyzed all 399 available samples independent of classification, the highest median values of primary metabolites in this study were found for mono-n-butyl phthalate (MnBP: 49.6 microg/l), followed by mono-isobutyl phthalate (MiBP: 44.9 microg/l), mono-benzyl phthalate (MBzP: 7.2 microg/l), and mono-2-ethylhexyl phthalate (MEHP: 4.9 microg/l). The median concentrations of the oxidized metabolites of DEHP were 8.3 microg/l for mono-(2-carboxymethylhexyl) phthalate (2cx-MMHP), 19.2 microg/l for mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP), 14.7 microg/l for mono-(2-ethyl-5-oxohexyl) phthalate (5oxo-MEHP), and 26.2 microg/l for mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP). The concentrations of the two DiNP secondary metabolites mono (oxoisononyl) phthalate (oxo-MiNP) and mono(hydroxyisononyl) phthalate (OH-MiNP) ranged from <LOD to 304 microg/l (median: 3.0 microg/l, 2.9 microg/g creatinine) and <LOD to 698 microg/l (median: 5.5 microg/l, 5.2 microg/g creatinine), respectively. Phthalate metabolite levels did not consistently differ by sex or age. There was substantial day-to-day variation of urinary levels with considerable within-subject variability. Intraclass correlation coefficients adjusted for sex and age ranged between 0.21 and 0.48 for unadjusted metabolite levels and between 0.20 and 0.57 for creatinine-adjusted levels. The secondary metabolites of DiNP were detectable in nearly all samples and were therefore sensitive biomarkers of DiNP exposure. Our results of within-subject variability suggest that exposure assessment should not be based on a single urine measurement.