Elsevier

Environmental Research

Volume 108, Issue 2, October 2008, Pages 260-267
Environmental Research

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

https://doi.org/10.1016/j.envres.2008.07.014Get rights and content

Abstract

Concern about potential health impacts of low-level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population is increasing. We measured levels of six dialkyl phosphate (DAP) metabolites of OP pesticides, a chlorpyrifos-specific metabolite (3,5,6-trichloro-2-pyridinol, TCPy), BPA, and 14 phthalate metabolites in urine samples of 100 pregnant women from the Generation R study, the Netherlands. The unadjusted and creatinine-adjusted concentrations were reported, and compared to National Health and Nutrition Examination Survey and other studies. In general, these metabolites were detectable in the urine of the women from the Generation R study and compared with other groups, they had relatively high-level exposures to OP pesticides and several phthalates but similar exposure to BPA. The median concentrations of total dimethyl (DM) metabolites was 264.0 nmol/g creatinine (Cr) and of total DAP was 316.0 nmol/g Cr. The median concentration of mono-ethyl phthalate (MEP) was 222.0 μg/g Cr; the median concentrations of mono-isobutyl phthalate (MiBP) and mono-n-butyl phthalate (MnBP) were above 50 μg/g Cr. The median concentrations of the three secondary metabolites of di-2-ethylhexyl phthalate (DEHP) were greater than 20 μg/g Cr. The data indicate that the Generation R study population provides a wide distribution of selected environmental exposures. Reasons for the relatively high levels and possible health effects need investigation.

Introduction

Potential health effects of low-level exposures to organophosphorus (OP) pesticides, bisphenol A (BPA), and phthalates among the general population have been investigated (Eskenazi et al., 2007; Swan et al., 2005; vom Saal et al., 2007). For example, associations of prenatal OP pesticide exposure with infant adverse neurodevelopment have been reported (Engel et al., 2007; Eskenazi et al., 2007). The National Toxicology Program (NTP) Review Panel (National Toxicology Program, 2007) and a Chapel Hill Expert Panel (vom Saal et al., 2007) reported on adverse health effects of low-level exposure to BPA in experimental animal studies. Experimental animal studies have also found reproductive and developmental toxicity of some phthalates (Kavlock et al., 2002) and in humans an association between prenatal phthalate exposure at general population levels and reduced anogenital distance has been reported (Swan et al., 2005). Each of these potential effects, however, requires greater study in humans. For such investigations, we need to identify environmentally exposed populations where health effects can be studied.

The widespread use of OP pesticides results in human exposure through a variety of sources including residues in food (Lu et al., 2006; National Research Council, 1993). Upon intake, most OP pesticides are metabolized to one or more of six dialkyl phosphate (DAP) metabolites (Duggan et al., 2003). Thus, levels of DAP metabolites in urine reflect exposure to one or more OP pesticides (Barr et al., 2004; Barr and Needham, 2002; Bradman et al., 2005; Duggan et al., 2003; Wessels et al., 2003). Chlorpyrifos is the most widely used OP pesticide worldwide. The major chlorpyrifos-specific metabolite in humans is 3,5,6-trichloro-2-pyridinol (TCPy). Levels of TCPy in urine have frequently been used as a biomarker of exposure to chlorpyrifos, triclopyr, and chlorpyrifos-methyl (Barr and Angerer, 2006).

BPA is used to manufacture polycarbonate plastics and epoxy resins. Human exposure to BPA can arise from multiple sources, particularly from food in contact with BPA containing materials and in some dental sealants (Kang et al., 2006). BPA is rapidly glucuronidated and excreted in urine (Tsai, 2006). Other minor metabolites identified include sulfate conjugates and glucuronide/sulfate diconjugates.

Phthalates are a family of related compounds used for a variety of purposes including personal care products and as a plasticizer in polyvinyl chloride plastics. Humans are exposed to phthalates through ingestion, inhalation and dermal contact (Latini, 2005). After entering the body, phthalates are rapidly metabolized to their respective monoesters, some of which can be further metabolized to oxidative metabolites (Hauser and Calafat, 2005). All these metabolites can be glucuronidated and excreted in the urine and feces. Measurements of metabolites in body fluids (mainly urine) are usually better biomarkers of exposure than those of the parent phthalates because the latter are easily affected by laboratory contamination (Barr et al., 2003). In most cases, the metabolite is more toxic than the parent phthalate (Peck and Albro, 1982).

In this paper, we report biological monitoring data on metabolites of OP pesticides, BPA, and phthalates among 100 pregnant women, a subset of participants in the Generation R study in Rotterdam, the Netherlands. This analysis was conducted to better understand exposure status of these pollutants among the general population. To our knowledge, this is the first report on the biological monitoring of these compounds among a general population in the Netherlands.

Section snippets

Study population

The Generation R study is a population-based birth cohort study in the city of Rotterdam that has been described in detail previously (Jaddoe et al., 2006). Briefly, all mothers who resided in the study area and had a delivery date between April 2002 and January 2006 were eligible. Mothers could be enrolled during pregnancy or in the first months after the birth of their child when newborns visited the routine child health centers. Among the 9778 mothers who participated in the study, 91% (n

Results

The subjects’ age ranged from 18 to 41 years, with a median of 30 years (Table 1). Nearly half (46%) of the subjects stated they were Dutch. Among 82 subjects who gave their education levels, 35% of them had at least some higher education. Sixty percent of the subjects stated that they did not smoke. Urine samples were collected during weeks 21–38 of pregnancy (median=30 weeks). Urinary creatinine ranged from 0.14 to 2.49 g/L (median=0.68 g/L).

Urinary metabolite levels are summarized for all

Discussion

The creatinine-adjusted median concentrations (nmol/g Cr) of total DM and total DAP among 100 pregnant women in the Generation R study (Fig. 1a) were higher than that of NHANES 2001–2002 pregnant women aged 15–44 years (Centers for Disease Control and Prevention, 2008), higher than that of pregnant women residing in an agricultural community in the Salinas Valley (The Center for the Health Assessment of Mothers and Children of Salinas, CHAMACOS), California (Bradman et al., 2005), and higher

Acknowledgments

The Generation R study is conducted by the Erasmus MC, University Medical Center, Rotterdam, the Netherlands in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, the Rotterdam Homecare Foundation and the Stichting Trombosedienst & Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of general practitioners, hospitals, midwives, and pharmacies in

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    Funding source: This study was supported by the Intramural Research Program, NIEHS and the Harvard NIEHS Environmental Health Center Pilot Project Grant P30ES000002.

    This study was approved by ethical committees in National Institutes of Health (NIH) and Erasmus MC.

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