Urinary phthalate/DINCH metabolites associations with kisspeptin and reproductive hormones in teenagers: A cross-sectional study from the HBM4EU aligned studies.

BACKGROUND: Exposure to phthalate/DINCH metabolites can induce human reproductive toxicity, however, their endocrine-disrupting mechanisms are not fully elucidated. OBJECTIVE: To investigate the association between concentrations of phthalate/DINCH metabolites, serum kisspeptin, and reproductive hormones among European teenagers from three of the HBM4EU Aligned Studies. METHODS: In 733 Belgian (FLEHS IV study), Slovak (PCB cohort follow-up), and Spanish (BEA study) teenagers, ten phthalate and two DINCH metabolites were measured in urine by high-performance liquid chromatography-tandem mass spectrometry. Serum kisspeptin (kiss54) protein, follicle-stimulating hormone (FSH), total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) levels were measured by immunosorbent assays. Free Androgen Index (FAI) was calculated as a proxy of free testosterone. Adjusted sex-stratified linear regression models for individual studies, mixed effect models (LME) accounting for random effects for pooled studies, and g-computation and Bayesian kernel machine regression (BKMR) models for the phthalate/DINCH mixture were performed. RESULTS: The LME suggested that each IQR increase in ln-transformed levels of several phthalates was associated with lower kisspeptin [MnBP: %change (95%CI): -2.8 (-4.2;-0.4); MEHP: -1.4 (-3.4,0.2)] and higher FSH [∑DINP: 11.8 (-0.6;25.1)] levels in females from pooled studies. G-computation showed that the phthalates/DINCH mixture was associated with lower kisspeptin [-4.28 (-8.07;-0.34)] and higher FSH [22.13 (0.5;48.4)] also in females; BKMR showed similar although non-significant pattern. In males, higher phthalates metabolites [MEHP: -12.22 (-21.09;-1.18); oxo-MEHP: -12.73 (-22.34;-1.93)] were associated with lower TT and FAI, although higher DINCH [OH-MINCH: 16.31 (6.23;27.35), cx-MINCH: 16.80 (7.03;27.46), ∑DINCH: 17.37 (7.26;29.74)] were associated with higher TT levels. No mixture associations were found in males. CONCLUSION: We observed sex-specific associations between urinary concentrations of phthalate/DINCH metabolites and the panel of selected effect biomarkers (kisspeptin and reproductive hormones). This suggests that exposure to phthalates would be associated with changes in kisspeptin levels, which would affect the HPG axis and thus influence reproductive health. However, further research is needed, particularly for phthalate replacements such as DINCH.

Nurse Mentoring: A Scoping Review.

INTRODUCTION: Mentoring programs minimize stress and anxiety in recent graduates and in newly recruited nurses, guiding their careers and enabling them to retain their skills and correctly care for patients. The objective of this scoping review is to explore and summarize the existing literature on mentoring models and programs in the clinical nursing context. METHODS: The databases searched include PubMed, Embase, Cochrane Library, Epistemonikos, Cuiden, Scielo, MEDES, OpenGrey, Trove and MedNar. Published and unpublished studies worldwide that included nurse mentoring programs in a clinical context, in public and private systems and primary, secondary and tertiary healthcare settings, and articles published in English, French, Spanish and Portuguese, were included. Nurse students and training specialists were excluded. The papers were screened by two independent reviewers. In cases of discrepancy, a third reviewer made the decision. RESULTS: Eleven studies were included. Most of them were conducted in the USA. A wide range of nurse mentoring programs were identified with highly variable characteristics. The duration of the programs and the evaluation systems were different, but the expected results matched. CONCLUSIONS: Mentoring programs need more in-depth and extensive study. In spite of their differences, they all lead to improvements for nurses, patients and organizations. A gender influence was found in our results, which could be studied in future research.

How back pain intensity relates to clinical and psychosocial factors in patients with idiopathic scoliosis.

OBJECTIVE: A pain intensity of 3 can reliably distinguish idiopathic scoliosis (IS) patients with acceptable pain or not. This research aims to analyze psychosocial, family and quality of life differences in patients according to their pain status. MATERIAL AND METHODS: Patients with IS, without previous surgery, Cobb ≥ 30° and age (12-40) were included in the study. They completed the questionnaires Numerical Rate Scale (NRS), Tampa Scale for Kinesiophobia (TSK)-11, SRS22r, Hospital Anxiety-Depression Scale (HADS), COMI item 7 (work/school absenteeism) and family APGAR. Comorbidities and family health history were collected. Analysis of covariance was performed to compare means between the PAIN (NRS > 3), (NRS < = 3) groups controlling for the effect of age and the magnitude of the curve. RESULTS: In total, 272 patients were included. 37.1% belonged to the PAIN group (PG). The PG showed a significantly higher Cobb grade and age than the NO-PAIN group. After controlling for these variables, the PG had worse pain, mental health and SRS22-subtotal values. However, they did not differ in function or self-image. PG showed higher levels of kinesiophobia, anxiety, depression, absenteeism from work/school and impact on social/family environment. PG patients reported a higher prevalence of comorbidities and family history of nonspecific spinal pain. CONCLUSIONS: Patients with IS and unacceptable pain constitute a group with a different incidence of psychological, social, family and comorbidities factors than those with acceptable pain. In contrast, the severity of IS was not substantially different between the groups. This profile is similar to that observed in patients with nonspecific spinal pain.

Mercury Levels in Feathers of Penguins from the Antarctic Peninsula Area: Geographical and Inter-Specific Differences.

Polar regions, symbols of wilderness, have been identified as potential sinks of mercury coming from natural and anthropogenic sources at lower latitudes. Changes in ice coverage currently occurring in some areas such as the Antarctic Peninsula could enhance these phenomena and their impacts on local biota. As long-lived species at the top of food chains, seabirds are particularly sensitive to this highly toxic metal with the capacity to be biomagnified. Specifically, their feathers can be useful for Hg monitoring since they mainly accumulate its most toxic and persistent form, methyl-Hg. To that end, feathers of gentoo (Pygoscelis papua), chinstrap (P. antarcticus), and Adélie penguins (P. adeliae) (n = 108) were collected by passive sampling in seven different locations throughout the Antarctic Peninsula area and analyzed by ICP-MS after microwave-digestion. More than 93% of the samples showed detectable Hg levels (range: 6.3-12,529.8 ng g-1 dry weight), and the highest ones were found in the feathers of chinstrap penguins from King George Island. Hg bioconcentration and biomagnification seem to be occurring in the Antarctic food web, giving rise to high but non-toxic Hg levels in penguins, similar to those previously found in Arctic seabirds.

Associations of multiple exposures to persistent toxic substances with the risk of hyperuricemia and subclinical uric acid levels in BIOAMBIENT.ES study.

Hyperuricemia is becoming a serious public health issue, which is highly influenced by environmental factors, although there is still controversial information on the potential influence of the exposure to Persistent Toxic Substances (PTSs) in the general population. In this study we aimed to assess the association. PTS exposure with uric acid homeostasis in a sample of the Spanish population. Participants were recruited during 2009-2010 in all the main geographical areas of Spain. Exposure to 34 PTSs was estimated by chemical analyses of serum levels of 6 Polychlorinated Biphenyls (PCBs, n = 950), 13 Organochlorine Pesticides (OCPs, n = 453), 6 Perfluoroalkyl Substances (PFAs, n = 755), 7 Polybrominated Diphenyl Ethers (PBDEs, n = 365), urinary Cadmium (n = 926), and Lead in whole blood (n = 882). The two study outcomes were defined as the prevalence of hyperuricemia in the study population and uric acid levels, the latter only in individuals with no previous diagnosis of hyperuricemia. Statistical analyses were performed by means of binomial logistic regression and linear regression, and mixture effects were screened using Weighted Quantile Sum Regression (WQS). Serum concentrations of γ-HCH, o,p´-DDE, PCB-138, PCB-153, PFOA, and urinary Cadmium were associated with an increased risk of hyperuricemia, while PBDE-153 showed an inverse association with the effect. Furthermore, exposure to Cadmium, PCB-138, and to PCB-153 was positively associated with uric acid levels. Results were consistent after lipid adjustment or standardization. WQS analyses revealed a major contribution of PCB-153 within the PCB mixture on both the risk of hyperuricemia and uric acid levels. Sensitivity analyses were performed by adjusting for dietary habits, fasting glucose and estimated glomerular filtration rate. Overall, we found novel associations between human exposure to mixtures of PTSs and disturbances in uric acid homeostasis. However, we cannot completely rule out potential residual confounding effect or reversed-causality related to the cross-sectional design.

Environmental health surveillance in a future European health information system.

BACKGROUND: To date Health information (HI) in the European Union does not comprise indicators or other information related to impacts of hazardous chemicals in consumer products, food, drinking water or air on the health status of the population. Therefore, we inventorised and evaluated the potential of environmental health surveillance and research data sources in the European population to provide HBM-based indicators of internal human exposure and health impact of relevant chemicals. METHODS: We established an up-dated inventory of European cross-sectional Human Biomonitoring (HBM) surveys and of birth cohorts, and compared chemicals and chemical groups addressed by HBM with indicators and health end points collected via European Core Health Indicators (ECHI), in birth registries, as well as in environmental and food data bases and health registries to see on how data collection could be aligned. Finally, we investigated study designs of HBM survey and health examination surveys for potential synergies. RESULTS: The inventory covers a total of 11 European cross-sectional national programmes and a large number of birth cohorts and includes information on study population, age groups, covered substances, sampled matrices, and frequency. The comparison of data collections shows that there are many overlaps between environmental chemicals with environmental and health reporting. HBM data could be linked with ECHI indicators for work-related risks, body mass index (BMI), and low birth weight, with perinatal disease, neurologic disorders, and some chronic diseases, or with data bases for e.g. indoor air, food, or consumer products. Existing initiatives to link data collections at European Environment Agency (EEA) and Joint Research Center (JRC) or at World Health Organization (WHO) are good options to further develop linkage of HBM with exposures sources and health end points. CONCLUSIONS: There is potential to use HBM based information in a number of public health policies, and this would help to align reporting to international commitments. Environmental health surveillance based on HBM and HBM-based indicators, is an excellent tool to inform public health policies about risks from environmental chemicals, and the EU health information system would benefit from additional HBM-based indicators for monitoring exposure burden from environmental chemicals. Considerable efforts are needed to align and establish routine data collections and to develop a surveillance system and indicators which may inform public health policies.

Differential contribution of animal and vegetable food items on persistent organic pollutant serum concentrations in Spanish adults. Data from BIOAMBIENT.ES project.

Diet is considered the main source of Persistent Organic Pollutant (POP) exposure in the general population, although there are still several gaps of knowledge regarding the differential contribution of main food groups. The aim of this study was to identify dietary patterns that contribute to human exposure to organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and Perfluoroalkyl Substances (PFASs). Study population (n=1880, 18-65years old) was recruited during 2009-2010 in all the main geographical areas of Spain. For this work, exposure was estimated by chemical analyses of serum levels of 6 PCBs (n=1880), 13 OCPs (n=934), and 6 (PFASs) in a subsample of 755 (n=755). Dietary habits and covariates were gathered via self-administered questionnaires. Data analyses were performed by means of multivariable linear regression and weighted quantile sum regression. Both the consumption of animal-based and plant-based food were positively associated with the individual concentrations of p,p´-DDE, hexachlorobenzene, and PCB-congeners -138, -153, and-180. The contribution of animal-based products was 2.1-4.0× stronger except in p,p´-DDE, to which both patterns had similar contributions. In PFASs only animal food was positively associated with the exposure levels. The main animal-based contributors to PCB exposure were fish (49-64%) and eggs (19-36%), while OCP concentrations were mainly influenced by dairy products (32-48%) and fish (47-48%). PFOA and PFHxS were mainly explained by cold-meat (34-37%), fish (25-26%), and eggs (19-21%), while PFOS and PFDA were primarily influenced by fish consumption (44-77%). In the case of plant-based items, fruits (25-82%) and vegetables (18-63%) accounted for the majority of the variability of PCB and OCP concentrations. Our results highlight the relevance of dietary POP exposure as well as the need for the consideration of nutritional interventions in public health programs aiming to reduce POP exposure in the general population.

Urinary Phthalate Concentrations in Mothers and Their Children in Ireland: Results of the DEMOCOPHES Human Biomonitoring Study.

Background: Phthalates are chemicals which are widespread in the environment. Although the impacts on health of such exposure are unclear, there is evidence of a possible impact on the incidence of a diverse range of diseases. Monitoring of human exposure to phthalates is therefore important. This study aimed to determine the extent of phthalate exposure among mothers and their children in both rural and urban areas in Ireland, and to identify factors associated with elevated concentrations. It formed part of the 'Demonstration of a study to Co-ordinate and Perform Human Biomonitoring on a European Scale' (DEMOCOPHES) pilot biomonitoring study. Methods: the concentration of phthalate metabolites were determined from a convenience sample of 120 mother/child pairs. The median age of the children was 8 years. A questionnaire was used to collect information regarding lifestyle and environmental conditions of the children and mothers. Rigorous quality assurance within DEMOCOPHES guaranteed the accuracy and international comparability of results. Results: Phthalate metabolites were detected in all of the samples from both children and mothers. Concentrations were significantly higher in respondents from families with lower educational attainment and in those exposed to such items as polyvinyl chloride (PVC), fast food and personal care products (PCP). Conclusions: The study demonstrates that human biomonitoring for assessing exposure to phthalates can be undertaken in Ireland and that the exposure of the population is widespread. Further work will be necessary before the consequences of this exposure are understood.

Perfluorinated alkyl substances in Spanish adults: Geographical distribution and determinants of exposure.

Per- and polyfluoroalkyl substances (PFAS) are widely found in humans and the environment. Their persistence, bioaccumulation and toxicity make them a source of increasing public health concern. In this study, we analyzed the concentrations and geographical distribution of six PFAS in the serum of 755 Spanish adults aged 18-65. The geometric mean concentrations (and P95 values) for PFOS (perfluoroctane sulfonate), PFOA (perfluorooctanoic acid), PFHxS (perfluorohexane sulfonate), PFNA (perfluorononanoic acid) and PFDA (perfluorodecanoic acid) were 7.67 (19.3), 1.99 (5.48), 0.91 (2.84), 0.96 (2.44) and 0.42 (0.99) µg/L, respectively. N-Methylperfluorooctane sulfonamide (N-MeFOSAA) was detected in only 3.3% of samples. Residents in northeast (Catalonia) and northwest of Spain (Galicia) were found to have the highest serum values, whereas residents in the Canary Islands had the lowest values for almost all PFAS. Men presented higher levels than women, and we confirm that lactation (breastfeeding) contributes to a reduced body burden for all PFAS in women. Our data provide new information on exposure to PFAS in a national cross section sample of Spanish adults, thus providing a proxy for reference values for the Spanish population and forming the base for following temporal trends in the future.

Organochlorinated pesticides levels in a representative sample of the Spanish adult population: The Bioambient.es project.

Organochlorinated pesticides (OCPs) were measured in a representative sample of Spanish adults within the Bioambient.es project, a nationwide human biomonitoring program promoted by Spanish Ministry of Agriculture, Food and Environment. The objective of Bioambient.es is to establish reference levels of environmental pollutants in the general population. Participants were recruited in 2009-2010 during their annual medical examination at work. Serum levels of thirteen OCPs were investigated: Aldrin, endrin, dieldrin, heptachlor, heptachlor-epoxide, dichlorodiphenyldichloroethylenes (DDEs), hexachlorobenzene (HCB), dichlorodiphenyltrichloroethanes (DDTs) and hexachlorocyclohexanes (HCHs) The highest concentrations were observed for DDE, HCB and ß-HCH. The 95th percentile, in ng/g lipids, were: 717.7 for 4,4-DDE, 160.4 for HCB and 107.2 for ß-HCH, while concentrations of aldrin, endrin, heptachlor, α-HCH, 2,4-DDT, 4,4-DDT and 2,4-DDE were markedly lower and detected in less than 10% of the samples. Significant differences (p<0.05) were found for DDE and HCB and seasonality, gender and age. Analyzing the geographical distribution, participants from the north of Spain had highest levels of HCB while those from the center of Spain had highest levels of 4,4-DDE. Comparing to earlier studies, the results indicated a sharp decline in the OCP concentrations in the Spanish population over time, and today values are in the same range or lower than those reported in similar studies worldwide, except for HCHs and HCB that presented higher levels than in other European countries and much higher than those observed in US and Canada. This study represents the first nationwide survey of exposure to OCPs in Spain and provides a background reference range for exposure to OCPs in the Spanish adult occupied population. These results will allow establishing reference values, observing temporal trends and identifying high exposure groups.

Human biomonitoring pilot study DEMOCOPHES in Germany: Contribution to a harmonized European approach.

Human biomonitoring (HBM) is an effective tool to assess human exposure to environmental pollutants, but comparable HBM data in Europe are lacking. In order to expedite harmonization of HBM studies on a European scale, the twin projects COPHES (Consortium to Perform Human Biomonitoring on a European Scale) and DEMOCOPHES (Demonstration of a study to Coordinate and Perform Human Biomonitoring on a European Scale) were formed, comprising 35 partners from 27 European countries. In COPHES a research scheme and guidelines were developed to exemplarily measure in a pilot study mercury in hair, cadmium, cotinine and several phthalate metabolites in urine of 6-11year old children and their mothers in an urban and a rural region. Seventeen European countries simultaneously conducted this cross-sectional DEMOCOPHES feasibility study. The German study population was taken in the city of Bochum and in the Higher Sauerland District, comprising 120 mother-child pairs. In the present paper features of the study implementation are presented. German exposure concentrations of the pollutants are reported and compared with European average concentrations from DEMOCOPHES and with those measured in the representative German Environmental Survey (GerES IV). German DEMOCOPHES concentrations for mercury and cotinine were lower than the European average. However, 47% of the children were still exposed to environmental tobacco smoke (ETS) outside their home, which gives further potential for enhancing protection of children from ETS. Compared with samples from the other European countries German participating children had lower concentrations of the phthalate metabolites MEP and of the sum of 3 DEHP-metabolites (MEHP, 5OH-MEHP and 5oxo-MEHP), about the same concentrations of the phthalate metabolites MBzP and MiBP and higher concentrations of the phthalate metabolite MnBP. 2.5% of the German children had concentrations of the sum of 4 DEHP-metabolites and 4.2% had concentrations of MnBP that exceeded health based guidance values, indicating reasons for concern. Continuous HBM is necessary to track changes of pollutant exposure over time. Therefore Germany will continue to cooperate on the harmonisation of European human biomonitoring to support the chemicals regulation with the best possible exposure data to protect Europe's people against environmental health risks.

Cadmium levels in a representative sample of the Spanish adult population: The BIOAMBIENT.ES project.

Urinary cadmium levels (U-Cd) were measured in 1770 adults (aged 18-65 years) as a representative sample of the Spanish workforce. The geometric mean (GM) was 0.28 µg/l with 95% CI: 0.27-0.32 µg/l (GM: 0.20 µg/g 95% CI: 0.18-022 µg/g creatinine). The 95% percentile was 1.03 µg/l. U-Cd increased with age, with women showing higher U-Cd than men (p<0.001; 0.24 µg/g vs 0.17 µg/g). A multivariate analysis confirmed that sex, age and smoking habit significantly influence U-Cd. Smoking habit increases U-Cd by ∼90% per 10 years of age, almost twice the increase observed for non-smoking. Female smokers had 85% higher U-Cd than non-smokers, whereas the corresponding value for male smokers and non-smokers was 45%. No regional differences were observed with respect to the national reference level. The Spanish population studied here exhibits similar urinary cadmium levels to its European counterparts in Germany and slightly lower levels than in France, the Czech Republic, Italy and the United Kingdom. This paper provides the first baseline information concerning cadmium exposure in the Spanish adult population on a national scale. As such, these findings will help us to establish reference levels, follow temporal trends and identify high-exposure groups, thereby enabling comparisons with other countries and contributing to the improvement of public health and environmental quality.

Pilot study testing a European human biomonitoring framework for biomarkers of chemical exposure in children and their mothers: experiences in the UK.

Exposure to a number of environmental chemicals in UK mothers and children has been assessed as part of the European biomonitoring pilot study, Demonstration of a Study to Coordinate and Perform Human Biomonitoring on a European Scale (DEMOCOPHES). For the European-funded project, 17 countries tested the biomonitoring guidelines and protocols developed by COPHES. The results from the pilot study in the UK are presented; 21 school children aged 6-11 years old and their mothers provided hair samples to measure mercury and urine samples, to measure cadmium, cotinine and several phthalate metabolites: mono(2-ethyl-5-hydroxyhexyl)phthalate (5OH-MEHP), mono(2-ethyl-5-oxo-hexyl)phthalate (5oxo-MEHP) and mono(2-ethylhexyl)phthalate (MEHP), mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), mono-benzyl phthalate (MBzP) and mono-n-butyl phthalate (MnBP). Questionnaire data was collected on environment, health and lifestyle. Mercury in hair was higher in children who reported frequent consumption of fish (geometric mean 0.35 µg/g) compared to those that ate fish less frequently (0.13 µg/g, p = 0.002). Cadmium accumulates with age as demonstrated by higher levels of urinary cadmium in the mothers (geometric mean 0.24 µg/L) than in the children(0.14 µg/L). None of the mothers reported being regular smokers, and this was evident with extremely low levels of cotinine measured (maximum value 3.6 µg/L in mothers, 2.4 µg/L in children). Very low levels of the phthalate metabolites were also measured in both mothers and children (geometric means in mothers: 5OH-MEHP 8.6 µg/L, 5oxo-MEHP 5.1 µg/L, MEHP 1.2 µg/L, MEP 26.8 µg/L, MiBP 17.0 µg/L, MBzP 1.6 µg/L and MnBP 13.5 µg/L; and in children: 5OH-MEHP 18.4 µg/L, 5oxo-MEHP 11.4 µg/L, MEHP 1.4 µg/L, MEP 14.3 µg/L, MiBP 25.8 µg/L, MBzP 3.5 µg/L and MnBP 22.6 µg/L). All measured biomarker levels were similar to or below population-based reference values published by the US National Health and Nutrition Examination Survey (NHANES) and Germany's GerES surveys. No results were above available health guidance values and were of no concern with regards to health. The framework and techniques learnt here will assist with future work on biomonitoring in the UK.

Urinary cotinine levels and environmental tobacco smoke in mothers and children of Romania, Portugal and Poland within the European human biomonitoring pilot study.

The aim of this study was to explore data from the DEMOCOPHES study population for Romania, Portugal and Poland, in order to assess smoking patterns and the extent of ETS exposure and compare the national study samples with reference to the respective anti-smoking laws. The subset of the DEMOCOPHES study sample consisted of 360 children and their mothers (120 in each of the three countries - Romania (RO), Portugal (PT) and Poland (PL). Smoking was assessed using a detailed questionnaire for the participants, which addresses both active and passive smoking. This assessment uses exposure-relevant questionnaire data, in particular on the home environment and residence, socio-demographic characteristics, lifestyle such as nutrition, smoking behavior, other exposure-relevant behavior and occupational history, as well as urinary cotinine and creatinine measurements. We performed general statistical analysis and innovative receiver operating characteristic (ROC) curve analyses. Smoking prevalence as evaluated by the questionnaire was generally high, and higher than official statistics, which suggests some under-reporting in the countries, particularly in Romania. Urinary cotinine levels provided biochemical confirmation of the high and similar smoking prevalence for the three countries. Concerning ETS exposure, Romania presented significantly higher levels, for children as well as for non-smoking mothers, with Portugal showing significantly lower levels. Compared to non-smoking mothers, the children showed relatively higher ETS exposure levels in all three countries. The established country-specific optimal cut-off values in urinary cotinine to distinguish smokers from non-smokers vary more than those to discriminate ETS exposure extent in non-smoking mothers and children. Although different between countries, these values are a valuable output to monitor effectiveness of both national antismoking laws and educational programs in the three countries. The findings of this study point to the urgent need for stronger, more effective and well enforced smoke-free legislation in the three countries.

Fish consumption patterns and hair mercury levels in children and their mothers in 17 EU countries.

The toxicity of methylmercury (MeHg) in humans is well established and the main source of exposure is via the consumption of large marine fish and mammals. Of particular concern are the potential neurodevelopmental effects of early life exposure to low-levels of MeHg. Therefore, it is important that pregnant women, children and women of childbearing age are, as far as possible, protected from MeHg exposure. Within the European project DEMOCOPHES, we have analyzed mercury (Hg) in hair in 1799 mother-child pairs from 17 European countries using a strictly harmonized protocol for mercury analysis. Parallel, harmonized questionnaires on dietary habits provided information on consumption patterns of fish and marine products. After hierarchical cluster analysis of consumption habits of the mother-child pairs, the DEMOCOPHES cohort can be classified into two branches of approximately similar size: one with high fish consumption (H) and another with low consumption (L). All countries have representatives in both branches, but Belgium, Denmark, Spain, Portugal and Sweden have twice as many or more mother-child pairs in H than in L. For Switzerland, Czech Republic, Hungary, Poland, Romania, Slovenia and Slovakia the situation is the opposite, with more representatives in L than H. There is a strong correlation (r=0.72) in hair mercury concentration between the mother and child in the same family, which indicates that they have a similar exposure situation. The clustering of mother-child pairs on basis of their fish consumption revealed some interesting patterns. One is that for the same sea fish consumption, other food items of marine origin, like seafood products or shellfish, contribute significantly to the mercury levels in hair. We conclude that additional studies are needed to assess and quantify exposure to mercury from seafood products, in particular. The cluster analysis also showed that 95% of mothers who consume once per week fish only, and no other marine products, have mercury levels 0.55 µg/g. Thus, the 95th percentile of the distribution in this group is only around half the US-EPA recommended threshold of 1 µg/g mercury in hair. Consumption of freshwater fish played a minor role in contributing to mercury exposure in the studied cohort. The DEMOCOPHES data shows that there are significant differences in MeHg exposure across the EU and that exposure is highly correlated with consumption of fish and marine products. Fish and marine products are key components of a healthy human diet and are important both traditionally and culturally in many parts of Europe. Therefore, the communication of the potential risks of mercury exposure needs to be carefully balanced to take into account traditional and cultural values as well as the potential health benefits from fish consumption. European harmonized human biomonitoring programs provide an additional dimension to national HMB programs and can assist national authorities to tailor mitigation and adaptation strategies (dietary advice, risk communication, etc.) to their country's specific requirements.

Urinary polycyclic aromatic hydrocarbon metabolites levels in a representative sample of the Spanish adult population: The BIOAMBIENT.ES project.

In 2009, the Spanish Ministry of Agriculture, Food and Environment promoted the BIOAMBIENT.ES project, a Human Biomonitoring program on the national scale to estimate reference levels of environmental pollutants on a representative sample of the Spanish adults. The present study focuses on polycyclic aromatic hydrocarbons (PAHs). The urinary metabolites 1-hydroxypyrene, 1-,2-,3-,4- and 9-hydroxyphenanthrene and 3-hydroxybenzo[a]pyrene were selected as indicators of PAH exposure. Urine samples from 957 subjects (16-65 years old) were collected during year 2009-2010. Geometric mean and 95th percentile for 1-hydroxypyrene in µg g(-1) creatinine were 0.117 (non-smoker: 0.079, smokers: 0.184) and 0.67 µg g(-1) creatinine (non-smokers: 0.31, smokers: 0.69) respectively. GM and 95th percentile for sum of hydroxyphenanthrenes in µg g(-1) creatinine were 0.130 (non-smokers: 0.089, smokers: 0.317) and 1.29 (non-smokers: 0.71, smokers: 1.51) respectively. 3-Hydroxybenzo[a]pyrene was below the limit of quantitation (0.05 µg L(-1)) in all cases. Significant differences (p<0.05) regarding smokers and non-smokers, coal and wood heating, body mass index and second hand smoke were found, while other variables like gender, age, or diet showed no significant association. The geographical distribution of the metabolites showed higher levels in people who lived in the north and northwest of Spain. The PAH metabolites levels found were in the same range or lower than those reported from other European countries and they were higher than those found in the U.S. This study represents the first nationwide survey of exposure to PAHs in Spain and provides a background reference range for exposure to PAHs in the Spanish adult occupied population.

Urinary levels of eight phthalate metabolites and bisphenol A in mother-child pairs from two Spanish locations.

Exposure to some phthalate diesters and bisphenol A in the general population is a cause of increasing concern because of their potential adverse effects on the reproductive and endocrine systems and their broad presence in foodstuff and consumer products. The aims of this work are to assess patterns of exposure to phthalates and bisphenol A in a pilot sample of Spanish mothers and their children, and to provide basic information to address priorities in future Spanish surveys/research. Urinary levels of eight phthalate metabolites and bisphenol A have been measured in samples from 120 mother-child pairs in one rural and one urban location in central Spain, recruited as part of the European project DEMOCOPHES. More than 96% of the participants were exposed to all the compounds studied here with generally higher levels in children than their mothers. The sum of secondary DEHP metabolites gave a GM of 33.3µg/g creatinine (95% CI 30.2-36.6) for mothers and 63.0µg/g creatinine (95% CI 56.8-69.8) for children. Mono-ethyl phthalate (MEP) was the metabolite with the highest levels, with geometric means (GM) of 150.8µg/g creatinine (95% CI 124.0-183.5) for mothers and 198.9µg/g creatinine (95% CI 165.2-239.6) for children. Bisphenol A urinary levels were relatively low with geometric means of 2.0µg/g (95% CI 1.6-2.4) for mothers and 2.01µg/g (95% CI 1.7-2.4) for children. Personal care products like body lotions and fragrances showed associations with MEHP, MEP, MnBP and cx-MiNP and canteen food with MBzP and bisphenol A. Exposure of mothers and their children are correlated, except for MEP. As phthalates and bisphenol A are non-persistent chemicals, a daily, intermittent exposure of the population is taking place.

The Danish contribution to the European DEMOCOPHES project: A description of cadmium, cotinine and mercury levels in Danish mother-child pairs and the perspectives of supplementary sampling and measurements.

Human biomonitoring (HBM) is an important tool, increasingly used for measuring true levels of the body burdens of environmental chemicals in the general population. In Europe, a harmonized HBM program was needed to open the possibility to compare levels across borders. To explore the prospect of a harmonized European HBM project, DEMOCOPHES (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) was completed in 17 European countries. The basic measurements performed in all implemented countries of DEMOCOPHES included cadmium, cotinine and phthalate metabolites in urine and mercury in hair. In the Danish participants, significant correlations between mothers and children for mercury in hair and cotinine in urine were found. Mercury in hair was further significantly associated with intake of fish and area of residence. Cadmium was positively associated with BMI in mothers and an association between cadmium and cotinine was also found. As expected high cotinine levels were found in smoking mothers. For both mercury and cadmium significantly higher concentrations were found in the mothers compared to their children. In Denmark, the DEMOCOPHES project was co-financed by the Danish ministries of health, environment and food safety. The co-financing ministries agreed to finance a number of supplementary measurements of substances of current toxicological, public and regulatory interest. This also included blood sampling from the participants. The collected urine and blood samples were analyzed for a range of other persistent and non-persistent environmental chemicals as well as two biomarkers of effect. The variety of supplementary measurements gives the researchers further information on the exposure status of the participants and creates a basis for valuable knowledge on the pattern of exposure to various chemicals.

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.

Policy recommendations and cost implications for a more sustainable framework for European human biomonitoring surveys.

The potential of Human Biomonitoring (HBM) in exposure characterisation and risk assessment is well established in the scientific HBM community and regulatory arena by many publications. The European Environment and Health Strategy as well as the Environment and Health Action Plan 2004-2010 of the European Commission recognised the value of HBM and the relevance and importance of coordination of HBM programmes in Europe. Based on existing and planned HBM projects and programmes of work and capabilities in Europe the Seventh Framework Programme (FP 7) funded COPHES (COnsortium to Perform Human Biomonitoring on a European Scale) to advance and improve comparability of HBM data across Europe. The pilot study protocol was tested in 17 European countries in the DEMOCOPHES feasibility study (DEMOnstration of a study to COordinate and Perform Human biomonitoring on a European Scale) cofunded (50%) under the LIFE+ programme of the European Commission. The potential of HBM in supporting and evaluating policy making (including e.g. REACH) and in awareness raising on environmental health, should significantly advance the process towards a fully operational, continuous, sustainable and scientifically based EU HBM programme. From a number of stakeholder activities during the past 10 years and the national engagement, a framework for sustainable HBM structure in Europe is recommended involving national institutions within environment, health and food as well as European institutions such as ECHA, EEA, and EFSA. An economic frame with shared cost implications for national and European institutions is suggested benefitting from the capacity building set up by COPHES/DEMOCOPHES.