Phthalate exposure in pregnant women and newborns – The urinary metabolite excretion pattern differs distinctly

https://doi.org/10.1016/j.ijheh.2013.01.006Get rights and content

Abstract

Some phthalates are endocrine disruptors and reproductive and developmental toxicants. Data on newborn phthalate exposure and elimination characteristics are scarce. We determined 21 urinary phthalate metabolites (indicating exposure to 11 parent phthalates) in two study approaches: in the first approach we collected the urine of 20 healthy newborns at days 2–5 post partum together with 47 urine samples of 7 women during pregnancy. In the second fine tuned approach we collected first urine samples of 9 healthy newborns together with their mother's urine shortly before birth. To ensure full and contamination free collection of the newborns first urines we used special adhesive urine bags for children. All urine samples revealed ubiquitous exposures to phthalates comparable to other populations. Metabolite levels in the newborns first day urine samples were generally lower than in all other samples. However, the newborns urines (both first and day 2–5 urines) showed a metabolite pattern distinctly different from the maternal and general population samples: in the newborns urines the carboxy-metabolites of the long chain phthalates (DEHP, DiNP, DiDP) were the by far dominant metabolites with a relative share in the metabolite spectrum up to 6 times higher than in maternal urine. Oppositely, for the short chain phthalates (DBP, DiBP) oxidized metabolites seemed to be less favored than the simple monoesters in the newborns urines. The skewed metabolite distribution in the newborns urine warrants further investigation in terms of early phthalate metabolism, the quantity of internal phthalate exposure of the fetus/newborn and its possible health effects.

Introduction

Phthalic acid esters, also known as phthalates, have been widely used as plasticizers in PVC (polyvinyl chloride) products, including building materials, toys and many other products of our daily use. Some phthalates are also used in non-PVC applications such as pesticide formulations, additives in the textile industry, personal care products, paints or adhesives. Therefore, phthalates have become ubiquitous chemicals and environmental contaminants (Wormuth et al., 2006).

Some phthalates are developmental and reproductive toxicants in rodents and have to be regarded as endocrine disruptors for humans (Foster, 2005). They have been shown to modulate the endogenous production of fetal testicular testosterone with critical effects related to functional and structural impairment of male reproduction and development. In addition to these effects an influence on pregnancy duration and birth length has also been described (Adibi et al., 2009, Latini et al., 2003a, Latini et al., 2005, Wolff et al., 2008). In general, the fetal development and the early infant life are regarded as the most vulnerable periods of phthalate exposure (NAS, 2008).

The exposure of women and older children has already been determined for some phthalates (e.g. Di-ethyl phthalate (DEP), Di-n-butyl phthalate (DnBP), Di(2-ethylhexyl) phthalate (DEHP)), with generally higher phthalate metabolite levels in children's than adults urine (Becker et al., 2009, Casas et al., 2011, Frederiksen et al., 2011, Kasper-Sonnenberg et al., 2011, Silva et al., 2004a). Nevertheless, data on healthy newborns together with their pregnant mothers have only rarely been published (Sathyanarayana et al., 2008a, Adibi et al., 2008, Latini et al., 2003b, Wittassek and Angerer, 2008). Some studies reported the excretion of DEHP metabolites in neonatal intensive care unit infants (Calafat et al., 2004, Koch et al., 2006, Weuve et al., 2006, Su et al., 2012). We are not aware of any study investigating newborns first urine samples. The aim of this study was to investigate the phthalate exposure of regular term pregnant women and newborns directly after birth by determining the most complete set of 21 urinary phthalate metabolites, including novel secondary oxidized metabolites (Table 1). Special focus was put on obtaining the newborns first urines and comparing their phthalate metabolite pattern with the pattern of their mothers.

Section snippets

Subjects and sample collection

Urine samples of obviously healthy newborns and pregnant women (Table 2A, Table 2B) were collected from 2008 to 2010 in Jena, Germany. All newborns were born at term after uncomplicated singleton pregnancy. All women had an uncomplicated pregnancy and were in the age group 30 ± 5 years and of normal body weight. Data concerning pregnancy were obtained from maternity records of the hospital. In the “newborns urine day 2–5” subpopulation (see below), urine collection was more successful after

Metabolite concentrations

The metabolite concentrations for the maternal urine samples (both subpopulations of pregnant women) and the newborn urine samples (newborns first urine and urines form day 2 to 5) are listed in Table 3. Of the 21 phthalate metabolites analyzed, 18 metabolites were detected in the majority of all samples; three metabolites (MnPeP, MCHP and MnOP) were below limit of quantification (LOQ) in all samples of maternal and newborn urine. In all 4 subpopulations metabolites of DEP, DnBP, DiBP, DEHP and

Discussion

The set of 21 phthalate metabolites analyzed represents the most extensive spectrum of metabolites currently available, including various secondary oxidized metabolites that are not prone to external contamination and ideal biomarkers of exposure because of their rather long half-times of elimination (Koch and Calafat, 2009). For the first time we report metabolite levels in first urines of healthy newborns. By analyzing these first urines we intended to determine the body burden of newborns

Conclusions

The presence of all phthalate metabolites already in the first urine of healthy newborns strongly indicates the possibility of a transplacental passage of these substances. Thus, the placenta does not seem to protect the developing fetus from a maternal phthalate exposure. Phthalate metabolites found in the first urines may result from a transplacental passage of the parent phthalate or its monoester or the oxidized metabolites. The fetal capacity to metabolize phthalates thus remains

Acknowledgements

The authors thank the families for taking part in our research study and midwifes of Jena University Hospital department of Obstetrics for their assistance.

References (54)

  • H.M. Koch et al.

    Phthalate exposure during cold plastisol application – a human biomonitoring study

    Toxicol. Lett.

    (2012)
  • H.M. Koch et al.

    Determination of secondary, oxidised di-iso-nonylphthalate (DINP) metabolites in human urine representative for the exposure to commercial DINP plasticizers

    J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci.

    (2007)
  • T. Mose et al.

    Phthalate monoesters in perfusate from a dual placenta perfusion system, the placenta tissue and umbilical cord blood

    Reprod. Toxicol.

    (2007)
  • R. Preuss et al.

    Biological monitoring of the five major metabolites of di-(2-ethylhexyl)phthalate (DEHP) in human urine using column-switching liquid chromatography–tandem mass spectrometry

    J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci.

    (2005)
  • S. Sathyanarayana et al.

    Maternal and infant urinary phthalate metabolite concentrations: are they related?

    Environ. Res.

    (2008)
  • T.M. Tan et al.

    UDP-glucuronyltransferase activity toward harmol in human liver and human fetal liver cells in culture

    Anal. Biochem.

    (1990)
  • S. Vandentorren et al.

    Bisphenol-A and phthalates contamination of urine samples by catheters in the Elfe pilot study: implications for large-scale biomonitoring studies

    Environ. Res.

    (2011)
  • M. Wittassek et al.

    Fetal exposure to phthalates – a pilot study

    Int. J. Hyg. Environ. Health

    (2009)
  • X. Ye et al.

    Urinary metabolite concentrations of organophosphorous pesticides, bisphenol a, and phthalates among pregnant women in Rotterdam, the Netherlands: the generation R study

    Environ. Res.

    (2008)
  • J.J. Adibi et al.

    Maternal urinary metabolites of di-(2-ethylhexyl) phthalate in relation to the timing of labor in a us multicenter pregnancy cohort study

    Am. J. Epidemiol.

    (2009)
  • J.J. Adibi et al.

    Characterization of phthalate exposure among pregnant women assessed by repeat air and urine samples

    Environ. Health Perspect.

    (2008)
  • J.W. Brock et al.

    Phthalate monoesters levels in the urine of young children

    Bull. Environ. Contam. Toxicol.

    (2002)
  • A.M. Calafat et al.

    Factors affecting the evaluation of biomonitoring data for human exposure assessment

    Int. J. Androl.

    (2008)
  • A.M. Calafat et al.

    What additional factors beyond state-of-the-art analytical methods are needed for optimal generation and interpretation of biomonitoring data?

    Environ. Health Perspect.

    (2009)
  • A.M. Calafat et al.

    Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit

    Pediatrics

    (2004)
  • CDC

    Fourth National Report on Human Exposure to Environmental Chemicals 2009; Updated Tables February 2011

    (2011)
  • R.A. Clewell et al.

    Tissue exposures to free and glucuronidated monobutylyphthalate in the pregnant and fetal rat following exposure to di-n-butylphthalate: evaluation with a PBPK model

    Toxicol. Sci.

    (2008)
  • Cited by (54)

    • Prenatal phthalate exposure measurement: A comparison of metabolites quantified in prenatal maternal urine and newborn's meconium

      2021, Science of the Total Environment
      Citation Excerpt :

      The ratio of DEHP metabolites have been previously used to evaluate differences in metabolism between adults and children (Enke et al., 2013). The ratio MEHHP/MEOHP in our sample was somewhat similar to reports in other studies using urine samples from pregnant women (Arbuckle et al., 2016; Enke et al., 2013), but the ratios MECPP/MEOHP and MECPP/MEHP were higher in EARLI than in Enke et al. In meconium samples we report only the ratio of the secondary metabolites of DEHP due to the potential for sample contamination affecting primary metabolites.

    • Pre- and early post-natal exposure to phthalates and DINCH in a new type of mother-child cohort relying on within-subject pools of repeated urine samples

      2021, Environmental Pollution
      Citation Excerpt :

      Interestingly, the distribution of each oxidized metabolite also differed by period. High MECPP/MEOHP and cx-MiNP/oxo-MinP ratios have also been reported in newborns (Enke et al., 2013), suggesting different DEHP and DiNP metabolism in the first months of life. These differences may attenuate with advanced child age as suggested by the values of the twelve-month ratios, which for DEHP metabolites, were closer to those observed during pregnancy than at two months.

    View all citing articles on Scopus
    View full text