ENDOCRINE DISRUPTORS BIOMONITORING IN CHILDREN: EXPOSURE ASSESSMENT AND OBESITY INCIDENCE

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Exposure assessment to bisphenol A (BPA) in Portuguese children by human biomonitoring

Publication . Correia-Sá, Luísa; Kasper-Sonnenberg, Monika; Schütze, André; Pälmke, Claudia; Norberto, Sónia; Calhau, Conceição; Domingues, Valentina; Koch, Holger M.

Exposure to bisphenol A (BPA) is known to be widespread and available data suggests that BPA can act as an endocrine disruptor. Diet is generally regarded as the dominant BPA exposure source, namely through leaching to food from packaging materials. The aim of this study was to evaluate the exposure of 110 Portuguese children (4-18 years old), divided in two groups: the regular diet group (n = 43) comprised healthy normal weight/underweight children with no dietary control; the healthy diet group (n = 67) comprised children diagnosed for obesity/overweight (without other known associated diseases) that were set on a healthy diet for weight control. First morning urine samples were collected and total urinary BPA was analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. Virtually, all the children were exposed to BPA, with 91% of the samples above the LOQ (limit of quantification) of 0.1 μg/L. The median (95th percentile) urinary BPA levels for non-normalized and creatinine-corrected values were 1.89 μg/L (16.0) and 1.92 μg/g creatinine (14.4), respectively. BPA levels in the regular diet group were higher than in the healthy diet group, but differences were not significant. Calculated daily BPA intakes, however, were significantly higher in children of the regular diet group than in children of healthy diet group. Median (95th percentile) daily intakes amounted to 41.6 (467) ng/kg body weight/day in the regular diet group, and 23.2 (197) ng/kg body weight/day in the healthy diet group. Multiple logistic regression analysis revealed that children in the healthy diet group had 33% lower intakes than children in the regular diet group (OR 0.67; 95% CI 0.51-0.89). For both groups, however, urinary BPA levels and daily BPA intakes were within the range reported for other children's populations and were well below health guidance values such as the European Food Safety Authority (EFSA) temporary tolerable daily intake (t-TDI) of 4 μg/kg body weight/day. In addition, lower daily BPA intakes were more likely linked with the inherent dietary approach rather than with high BMI or obesity.

2017Journal article

Open access

Obesity or diet? Levels and determinants of phthalate body burden – A case study on Portuguese children

Publication . Correia-Sá, Luísa; Kasper-Sonnenberg, Monika; Pälmke, Claudia; Schütze, André; Norberto, Sónia; Calhau, Conceição; Domingues, Valentina F.; Koch, Holger M.

In this study we analyzed one of the most comprehensive sets of 21 urinary phthalate metabolites representing exposure to 11 parent phthalates (DEP, DMP, DiBP, DnBP, BBzP, DEHP, DiNP, DiDP, DCHP, DnPeP, DnOP) in first morning urine samples of 112 Portuguese children (4-18 years) sampled in 2014/15. The study population consisted of two groups: group 1 with normal weight/underweight children (N = 43) following their regular diet and group 2 with obese/overweight children (N = 69) following a healthy diet (with nutritional counselling). Most of the metabolites were above the limits quantification (81-100%) except for MCHP, MnPEP and MnOP. Metabolite levels were generally comparable to other recent child and general populations sampled worldwide, confirming the steady decline in exposures to most phthalates. Compared to Portuguese children sampled in 2011/2012, median urinary metabolite levels decreased by approximately 50% for DEHP, DnBP, DiBP and BBzP. Risk assessments for individual phthalates and the sum of the anti-androgenic phthalates did not indicate to attributable health risks, also at the upper percentiles of exposure. In the healthy diet group the median concentration of the DEHP metabolites was significant lower, while all phthalate metabolites except MEP tended to be lower compared to the regular diet group. Multiple log-linear regression analyses revealed significantly lower daily intakes (DIs) for all phthalates in the healthy diet group compared to the regular diet group (geometric mean ratios (gMR) between 0.510-0.618; p ≤ 0.05), except for DEP (gMR: 0.811; p = 0.273). The same analyses with the continuous variable body mass index instead of the diet groups also showed effects on the DIs (gMRs between 0.926-0.951; p ≤ 0.05), however much smaller than the effects of the diet. The results indicate that obese children following a healthy diet composed of fresh and less packaged/processed food can considerably reduce their intake for most phthalates and can have lower phthalate intakes than regular weight/regular diet children.

2018Journal article

Open access

Micro-QuEChERS extraction coupled to GC–MS for a fast determination of Bisphenol A in human urine

Publication . Correia-Sá, Luísa; Norberto, Sónia; Delerue-Matos, Cristina; Calhau, Conceição; Domingues, Valentina F.

Bisphenol A (BPA) is considered an endocrine disruptor and public concern over BPA exposure has been raised. Several studies have assessed human exposure to this plasticizer, confirming its ubiquitous presence and highlighting children as a public of special concern. A simple, efficient, cheap and green analytical procedure is reported within this paper. This paper reports, for the first time, the development of a modified Micro-QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method coupled to gas chromatography-mass spectrometry (GC-MS) as a new strategy for the efficient extraction and determination of Bisphenol A in human urine samples. Several parameters that are known to influence extraction were optimized. Good linearity was achieved at the studied concentration range (1-50μg/L), with a correlation coefficient (R2) of 0.998. The optimized method proved to be accurate (≥74% recovery), reproducible (<11% relative standard deviation) and sensitive for BPA determination (detection limit of 0.13μg/L and quantification limit of 0.43μg/L). The analytical procedure was applied to the analyses of 12 urine samples collected from children living in the North/Center region of Portugal. BPA was detected in all the analyzed samples in concentrations ranging from 1.5μg/L to 48.9μg/L. The proposed methodology is suitable for the determination of BPA in urine samples in the framework of biomonitoring studies and bioanalytical analyses, applying GC-MS detection.

2018Journal article

Open access

Exposure of Portuguese children to the novel non-phthalate plasticizer di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH)

Publication . Correia-Sá, Luísa; Schütze, André; Norberto, Sónia; Calhau, Conceição; Domingues, Valentina; Koch, Holger M.

Di-(iso-nonyl)-cyclohexane-1,2-dicarboxylate (DINCH) is used as substitute for high molecular weight phthalate plasticizers such as di-(2-ethylhexyl) phthalate (DEHP) and di-(iso-nonyl) phthalate (DINP). Due to a rapid substitution process we have to assume omnipresent and increasing DINCH exposures. The aim of this study was to evaluate DINCH exposure in 112 children (4-18years old) from Portugal, divided in two groups: 1) normal-/underweight following the usual diet; and 2) obese/overweight but under strict nutritional guidance. First morning urine samples were collected during the years 2014 and 2015. Oxidized DINCH metabolites (OH-MINCH, oxo-MINCH, cx-MINCH) were analyzed after enzymatic hydrolysis via on-line HPLC-MS/MS with isotope dilution quantification. We detected DINCH metabolites in all analyzed samples. Urinary median (95th percentile) concentrations were 2.14μg/L (15.91) for OH-MINCH, followed by 1.10μg/L (7.54) for oxo-MINCH and 1.08μg/L (7.33) for cx-MINCH. We observed no significant differences between the two child-groups; only after creatinine adjustment, we found higher metabolite concentrations in the younger compared to the older children. Median (95th percentile) daily DINCH intakes were in the range of 0.37 to 0.76 (2.52 to 5.61) μg/kg body weight/day depending on calculation model and subpopulation. Body weight related daily intakes were somewhat higher in Group 1 compared to Group 2, irrespective of the calculation model. However, in terms of absolute amounts (μg/day), DINCH intakes were higher in Group 2 compared to Group 1. In regard to age, we calculated higher intakes for the younger children compared to older children, but only with the creatinine-based model. This new data for southern European, Portuguese children adds information to the scarce knowledge on DINCH, confirming omnipresent exposure and suggesting higher exposures in children than adults. Significant sources and routes of exposure have yet to be unveiled. For now, all calculated daily intakes are far below established health benchmark levels (TDI, RfD). However, rapidly increasing exposures have to be expected over the next years.

2017Journal article

Open access