Abstract

Our objectives were (1) to evaluate whether single spot urine is suitable media for longer-term phthalate esters exposure assessment, and (2) to estimate intake level of phthalate esters of Japanese pregnant women using urinary metabolites as an indicator of prenatal exposure level in their offspring. We analyzed nine metabolites (MMP, MEP, MnBP, MBzP, MEHP, MEOHP, MEHHP, MINP, MnOP) of seven phthalate esters in spot urine samples from 50 pregnant women by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using four urine samples collected from each of 12 subjects from 50 pregnant women within 5-12 weeks, we compared intra- and interindividual variation in urinary metabolites by calculation of intraclass correlation coefficient (ICC). We estimated daily intakes of 50 pregnant women from their urinary metabolite concentrations. ICCs for seven phthalate metabolite concentrations in single spot urine samples were: MMP (0.57), MEP (0.47), MnBP (0.69), MBzP (0.28), MEHP (0.51), MEHHP (0.43), and MEOHP (0.41) in 12 pregnant women. Phthalate ester metabolites had high detection rates in 50 subjects. The mean daily intake ranged from 0.01 to 2 mug/kg per day. The daily intake levels in all subjects were lower than corresponding tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA), though maximum value for DnBP of 6.91 mug/kg per day accounted for 70% of TDI value. Higher ICCs indicated that phthalate metabolite levels in single spot urine could reflect longer-term exposure to the corresponding diesters of subjects. Although the current exposure level was less than TDIs, further studies and exposure monitoring are needed to reveal the toxicity of phthalate esters to sensitive subpopulation.

Highlights

  • Phthalate esters are produced in abundance all over the world because of their multiple uses

  • The daily intake levels in all subjects were lower than corresponding tolerable daily intake (TDI) set by the European Food Safety Authority (EFSA), though maximum value for di-n-butyl phthalate (DnBP) of 6.91 lg/kg per day accounted for 70% of TDI value

  • Higher intraclass correlation coefficient (ICC) indicated that phthalate metabolite levels in single spot urine could reflect longer-term exposure to the corresponding diesters of subjects

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Summary

Introduction

Phthalate esters are produced in abundance all over the world because of their multiple uses. Di(2ethylhexyl)phthalate (DEHP) has been produced as one of the major plasticizers for many years [1]. Other phthalate esters, such as di-n-butyl phthalate (DnBP) and diethyl phthalate (DEP), are used in paints and consumer products, and as plasticizers [2, 3]. The recognition that some phthalate esters have adverse effects on male reproductive system in experimental animals, especially via in utero exposure, has been increasing [4]. Testosterone production of fetal male rodent is reduced following in utero phthalate ester exposure, which results in malformation of male reproductive tract, such as reduced anogenital distance (AGD), retained nipples, hypospadias, cleft phallus, undescended testis epididymal agenesis, and testicular atrophy [5, 6]

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