Exposure to environmental phthalates during preschool age and obesity from childhood to young adulthood.

Obesity rates are increasing globally, and recent theories suggest that phthalates may contribute to obesity development. This longitudinal study aimed to investigate associations between environmental phthalate exposure during childhood and obesity, utilizing data from 100 participants from a Swedish birth cohort. The participants were followed repeatedly from birth and provided spot urine samples at 4 years. Weight and height were measured at ages 4, 8, 16 and 24 years, as well as additional anthropometric indices at 24 years. Urine samples were analysed for 10 phthalate metabolites using liquid chromatography tandem mass spectrometry. Generalized estimating equation models were performed to assess overall and age-specific associations between urinary phthalate concentrations and BMI groups; thin/normal weight vs overweight/obese. After adjustment for potential confounders, overall associations were observed for diisononyl phthalate (DiNP) metabolites mono(oxo-isononyl) phthalate (MOiNP) (OR per increase ng/ml: 1.18; 95% CI: 1.05, 1.33), mono(carboxy-isooctyl) phthalate (MCiOP) (OR: 1.06; 95% CI: 1.01, 1.11) and ∑DiNP (OR: 1.02; 95% CI:1.00, 1.04) and development of overweight/obesity up to age 24 years. Age-specific associations were observed for the same metabolites at 8, 16 and 24 years. Furthermore, linear regression analysis revealed associations between increased body fat % at age 24 years and MHiNP (ß: 2.42; 95% CI: 0.44, 4.39), MOiNP (ß: 2.32; 95% CI: 0.46, 4.18), MCiOP (ß: 2.65; 95% CI: 0.41, 4.89) and ∑DiNP (ß: 2.65; 95% CI: 0.52, 4.77). These findings suggest that DiNP exposure during preschool age may be associated with subsequent obesity, however these findings need to be corroborated by further research.

Brominated Flame Retardants and Organophosphate Esters in Preschool Dust and Children's Hand Wipes.

Children spend a considerable part of their day in preschool, where they may be exposed to hazardous chemicals in indoor dust. In this study, brominated flame retardants (BFRs) and organophosphate esters (OPEs) were analyzed in preschool dust ( n = 100) and children's hand wipe samples ( n = 100), and diphenyl phosphate (DPHP) was analyzed in urine ( n = 113). Here we assessed children's exposure via dust, identified predictors for chemicals in dust, and studied correlations between different exposure measures. The most abundant BFRs in dust were decabromodiphenyl ether (BDE-209) and decabromodiphenyl ethane (DBDPE) found at median levels of 270 and 110 ng/g dust, respectively. Tris(2-butoxyethyl) phosphate (TBOEP) was the most abundant OPE, found at a median level of 79 000 ng/g dust. For all OPEs and some BFRs, there were significant correlations between the levels in dust and hand wipes. In addition, triphenyl phosphate (TPHP) in preschool dust was significantly correlated with the corresponding metabolite DPHP in children's urine. The levels of pentaBDEs in dust were higher in older preschools compared with newer, whereas levels of DBDPE were higher in newer preschools. Children's estimated intakes of individual BFRs and OPEs via preschool dust were below available health-based reference values. However, there are uncertainties about the potential health effects of some emerging BFRs and OPEs.

Phthalates, non-phthalate plasticizers and bisphenols in Swedish preschool dust in relation to children's exposure.

Children are exposed to a wide range of chemicals in their everyday environments, including the preschool. In this study, we evaluated the levels of phthalates, non-phthalate plasticizers and bisphenols in dust from 100 Swedish preschools and identified important exposure factors in the indoor environment. In addition, children's total exposure to these chemicals was determined by urine analysis to investigate their relation with dust exposure, and to explore the time trends by comparing with children who provided urine fifteen years earlier. The most abundant plasticizers in preschool dust were the phthalates di-isononyl phthalate (DiNP) and di-(2-ethylhexyl) phthalate (DEHP) with geometric mean levels of 450 and 266µg/g dust, respectively, and the non-phthalate plasticizers bis(2-ethylhexyl) terephthalate (DEHT) and diisononylcyclohexane-1,2-dicarboxylate (DiNCH) found at 105 and 73µg/g dust, respectively. The levels of several substitute plasticizers were higher in newer preschools, whereas the levels of the strictly regulated phthalate di-n-butyl phthalate (DnBP) were higher in older preschools. The presence of foam mattresses and PVC flooring in the sampling room were associated with higher levels of DiNP in dust. Children's exposure from preschool dust ingestion was below established health based reference values and the estimated exposure to different phthalates and BPA via preschool dust ingestion accounted for 2-27% of the total exposure. We found significantly lower urinary levels of BPA and metabolites of strictly regulated phthalates, but higher levels of DiNP metabolites, in urine from the children in this study compared to the children who provided urine samples fifteen years earlier.

Text mining for improved exposure assessment.

Chemical exposure assessments are based on information collected via different methods, such as biomonitoring, personal monitoring, environmental monitoring and questionnaires. The vast amount of chemical-specific exposure information available from web-based databases, such as PubMed, is undoubtedly a great asset to the scientific community. However, manual retrieval of relevant published information is an extremely time consuming task and overviewing the data is nearly impossible. Here, we present the development of an automatic classifier for chemical exposure information. First, nearly 3700 abstracts were manually annotated by an expert in exposure sciences according to a taxonomy exclusively created for exposure information. Natural Language Processing (NLP) techniques were used to extract semantic and syntactic features relevant to chemical exposure text. Using these features, we trained a supervised machine learning algorithm to automatically classify PubMed abstracts according to the exposure taxonomy. The resulting classifier demonstrates good performance in the intrinsic evaluation. We also show that the classifier improves information retrieval of chemical exposure data compared to keyword-based PubMed searches. Case studies demonstrate that the classifier can be used to assist researchers by facilitating information retrieval and classification, enabling data gap recognition and overviewing available scientific literature using chemical-specific publication profiles. Finally, we identify challenges to be addressed in future development of the system.

Exposure determinants of cadmium in European mothers and their children.

The metal cadmium (Cd) is a widespread environmental pollutant with documented adverse effects on the kidneys and bones from long-term environmental exposure, but with insufficiently elucidated public health consequences such as risk of cardiovascular disease, hormone-related cancer in adults and developmental effects in children. This study is the first pan-European human biomonitoring project that succeeded in performing harmonized measurements of Cd in urine in a comparable way in mother-child couples from 16 European countries. The aim of the study was to evaluate the overall Cd exposure and significant determinants of Cd exposure. A study population of 1632 women (24-52 years of age), and 1689 children (5-12 years of age), from 32 rural and urban areas, was examined within a core period of 6 months in 2011-2012. Women were stratified as smokers and non-smokers. As expected, smoking mothers had higher geometric mean (gm) urinary cadmium (UCd; 0.24 µg/g crea; n=360) than non-smoking mothers (gm 0.18 µg/g crea; n=1272; p<0.0001), and children had lower UCd (gm 0.065 µg/g crea; n=1689) than their mothers at the country level. Non-smoking women exposed to environmental tobacco smoke (ETS) at home had 14% (95% CI 1-28%) higher UCd than those who were not exposed to ETS at home (p=0.04). No influence of ETS at home or other places on UCd levels was detected in children. Smoking women with primary education as the highest educational level of the household had 48% (95% CI 18-86%) higher UCd than those with tertiary education (p=0.0008). The same observation was seen in non-smoking women and in children; however they were not statistically significant. In children, living in a rural area was associated with 7% (95% CI 1-13%) higher UCd (p=0.03) compared to living in an urban area. Children, 9-12 years had 7% (95% CI 1-13%) higher UCd (p=0.04) than children 5-8 years. About 1% of the mothers, and 0.06% of the children, exceeded the tolerable weekly intake (TWI) appointed by EFSA, corresponding to 1.0 µg Cd/g crea in urine. Poland had the highest UCd in comparison between the 16 countries, while Denmark had the lowest. Whether the differences between countries are related to differences in the degree of environmental Cd contamination or to differences in lifestyle, socioeconomic status or dietary patterns is not clear.

Lessons learnt on recruitment and fieldwork from a pilot European human biomonitoring survey.

Within the European Environment and Health Action Plan an initiative to establish a coherent human biomonitoring approach in Europe was started. The project COPHES (COnsortium to Perform Human biomonitoring on a European Scale ) developed recommendations for a harmonized conduct of a human biomonitoring (HBM) survey which came into action as the pilot study DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale). Seventeen European countries conducted a survey with harmonized instruments for, inter alia, recruitment, fieldwork and sampling, in autumn/winter 2011/2012. Based on the countries' experiences of conducting the pilot study, following lessons learnt were compiled: the harmonized fieldwork instruments (basic questionnaire, urine and hair sampling) turned out to be very valuable for future HBM surveys on the European scale. A school approach was favoured by most of the countries to recruit school-aged children according to the established guidelines and country specific experiences. To avoid a low participation rate, intensive communication with the involved institutions and possible participants proved to be necessary. The communication material should also include information on exclusion criteria and offered incentives. Telephone contact to the participants the day before fieldwork during the survey can prevent the forgetting of appointments and first morning urine samples. To achieve comparable results on the European scale, training of interviewers in all issues of recruitment, fieldwork and sampling through information material and training sessions is crucial. A survey involving many European countries needs time for preparation and conduct. Materials for quality control prepared for all steps of recruitment, fieldwork and sampling proved to be important to warrant reliable results.

Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.

For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12 y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300 mg/L or above 3000 mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.

First steps toward harmonized human biomonitoring in Europe: demonstration project to perform human biomonitoring on a European scale.

BACKGROUND: For Europe as a whole, data on internal exposure to environmental chemicals do not yet exist. Characterization of the internal individual chemical environment is expected to enhance understanding of the environmental threats to health. OBJECTIVES: We developed and applied a harmonized protocol to collect comparable human biomonitoring data all over Europe. METHODS: In 17 European countries, we measured mercury in hair and cotinine, phthalate metabolites, and cadmium in urine of 1,844 children (5-11 years of age) and their mothers. Specimens were collected over a 5-month period in 2011-2012. We obtained information on personal characteristics, environment, and lifestyle. We used the resulting database to compare concentrations of exposure biomarkers within Europe, to identify determinants of exposure, and to compare exposure biomarkers with health-based guidelines. RESULTS: Biomarker concentrations showed a wide variability in the European population. However, levels in children and mothers were highly correlated. Most biomarker concentrations were below the health-based guidance values. CONCLUSIONS: We have taken the first steps to assess personal chemical exposures in Europe as a whole. Key success factors were the harmonized protocol development, intensive training and capacity building for field work, chemical analysis and communication, as well as stringent quality control programs for chemical and data analysis. Our project demonstrates the feasibility of a Europe-wide human biomonitoring framework to support the decision-making process of environmental measures to protect public health.

Communication in a Human biomonitoring study: Focus group work, public engagement and lessons learnt in 17 European countries.

A communication strategy was developed by The Consortium to Perform Human Biomonitoring on a European Scale (COPHES), as part of its objectives to develop a framework and protocols to enable the collection of comparable human biomonitoring data throughout Europe. The framework and protocols were tested in the pilot study DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human biomonitoring on a European Scale). The aims of the communication strategy were to raise awareness of human biomonitoring, encourage participation in the study and to communicate the study results and their public health significance. It identified the audiences and key messages, documented the procedure for dissemination of results and was updated as the project progressed. A communication plan listed the tools and materials such as press releases, flyers, recruitment letters and information leaflets required for each audience with a time frame for releasing them. Public insight research was used to evaluate the recruitment material, and the feedback was used to improve the documents. Dissemination of results was coordinated in a step by step approach by the participating countries within DEMOCOPHES, taking into account specific national messages according to the needs of each country. Participants received individual results, unless they refused to be informed, along with guidance on what the results meant. The aggregate results and policy recommendations were then communicated to the general public and stakeholders, followed by dissemination at European level. Several lessons were learnt that may assist other future human biomonitoring studies. Recruitment took longer than anticipated and so social scientists, to help with community engagement, should be part of the research team from the start. As a European study, involving multiple countries, additional considerations were needed for the numerous organisations, different languages, cultures, policies and priorities. Therefore, communication documents should be seen as templates with essential information clearly indicated and the option for each country to tailor the material to reflect these differences. Future studies should consider setting up multidisciplinary networks of medical professionals and communication experts, and holding training workshops to discuss the interpretation of results and risk communication. Publicity and wide dissemination of the results helped to raise awareness of human biomonitoring to the general public, policy makers and other key stakeholders. Effective and timely communication, at all stages of a study, is essential if the potential of human biomonitoring research to improve public health is to be realised.

Exposure determinants of phthalates, parabens, bisphenol A and triclosan in Swedish mothers and their children.

Chemicals such as phthalates, parabens, bisphenol A (BPA) and triclosan (TCS), used in a wide variety of consumer products, are suspected endocrine disrupters although their level of toxicity is thought to be low. Combined exposure may occur through ingestion, inhalation and dermal exposure, and their toxic as well as combined effects are poorly understood. The objective of the study was to estimate the exposure to these chemicals in Swedish mothers and their children (6-11 years old) and investigate potential predictors of the exposure. Urine samples from 98 mother-child couples living in either a rural or an urban area were analyzed for the concentrations of four metabolites of di-(2-ethylhexyl) phthalate (DEHP), three metabolites of di-iso-nonyl phthalate (DiNP), mono-ethyl phthalate (MEP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP), methylparaben (MetP), ethylparaben (EthP), propylparaben (ProP), butylparaben, benzylparaben, BPA, and TCS. Information on sociodemographics, food consumption habits and use of personal care products, obtained via a questionnaire, was used to investigate the associations between the urinary levels of chemicals and potential exposure factors. There were fairly good correlations of biomarker levels between the mothers and their children. The children had generally higher levels of phthalates (geometric mean ΣDEHP 65.5 µg/L; ΣDiNP 37.8 µg/L; MBzP 19.9 µg/L; MnBP 76.9 µg/L) than the mothers (ΣDEHP 38.4 µg/L; ΣDiNP 33.8 µg/L; MBzP 12.8 µg/L; MnBP 63.0 µg/L). Conversely, the mother's levels of parabens (MetP 37.8 µg/L; ProP 13.9 µg/L) and MEP (43.4 µg/L) were higher than the children's levels of parabens (MetP 6.8 µg/L; ProP 2.1 µg/L) and MEP (28.8 µg/L). The urinary levels of low molecular weight phthalates were higher among mothers and children in the rural area (MBzP p=<0.001; MnBP p=0.001-0.002), which is probably due to higher presence of PVC in floorings and wall coverings in this area, whereas the levels of parabens were higher among the children in the urban area (MetP p=0.003; ProP p=0.004) than in the rural area. The levels of high molecular weight phthalates were associated with consumption of certain foods (i.e. chocolate and ice cream) whereas the levels of parabens were associated with use of cosmetics and personal care products.