Time Patterns in Internal Human Exposure Data to Bisphenols, Phthalates, DINCH, Organophosphate Flame Retardants, Cadmium and Polyaromatic Hydrocarbons in Europe.

Human biomonitoring (HBM) data in Europe are often fragmented and collected in different EU countries and sampling periods. Exposure levels for children and adult women in Europe were evaluated over time. For the period 2000-2010, literature and aggregated data were collected in a harmonized way across studies. Between 2011-2012, biobanked samples from the DEMOCOPHES project were used. For 2014-2021, HBM data were generated within the HBM4EU Aligned Studies. Time patterns on internal exposure were evaluated visually and statistically using the 50th and 90th percentiles (P50/P90) for phthalates/DINCH and organophosphorus flame retardants (OPFRs) in children (5-12 years), and cadmium, bisphenols and polycyclic aromatic hydrocarbons (PAHs) in women (24-52 years). Restricted phthalate metabolites show decreasing patterns for children. Phthalate substitute, DINCH, shows a non-significant increasing pattern. For OPFRs, no trends were statistically significant. For women, BPA shows a clear decreasing pattern, while substitutes BPF and BPS show an increasing pattern coinciding with the BPA restrictions introduced. No clear patterns are observed for PAHs or cadmium. Although the causal relations were not studied as such, exposure levels to chemicals restricted at EU level visually decreased, while the levels for some of their substitutes increased. The results support policy efficacy monitoring and the policy-supportive role played by HBM.

A regional comparison of children's blood cadmium, lead, and mercury in rural, urban and industrial areas of six European countries, and China, Ecuador, and Morocco.

OBJECTIVES: The authors aimed to evaluate whether blood cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) in children differ regionally in 9 countries, and to identify factors correlating with exposure. MATERIAL AND METHODS: The authors performed a cross-sectional study of children aged 7-14 years, living in 2007-2008 in urban, rural, or potentially polluted ("hot spot") areas (ca. 50 children from each area, in total 1363 children) in 6 European and 3 non-European countries. The authors analyzed Cd, Pb, and total Hg in blood and collected information on potential determinants of exposure through questionnaires. Regional differences in exposure levels were assessed within each country. RESULTS: Children living near industrial "hot-spots" had B-Cd 1.6 (95% CI: 1.4-1.9) times higher in the Czech Republic and 2.1 (95% CI:1.6-2.8) times higher in Poland, as compared to urban children in the same countries (geometric means [GM]: 0.13 µg/l and 0.15 µg/l, respectively). Correspondingly, B-Pb in the "hot spot" areas was 1.8 (95% CI: 1.6-2.1) times higher than in urban areas in Slovakia and 2.3 (95% CI: 1.9-2.7) times higher in Poland (urban GM: 19.4 µg/l and 16.3 µg/l, respectively). In China and Morocco, rural children had significantly lower B-Pb than urban ones (urban GM: 64 µg/l and 71 µg/l, respectively), suggesting urban exposure from leaded petrol, water pipes and/or coal-burning. Hg "hot spot" areas in China had B-Hg 3.1 (95% CI: 2.7-3.5) times higher, and Ecuador 1.5 (95% CI: 1.2-1.9) times higher, as compared to urban areas (urban GM: 2.45 µg/l and 3.23 µg/l, respectively). Besides industrial exposure, traffic correlated with B-Cd; male sex, environmental tobacco smoke, and offal consumption with B-Pb; and fish consumption and amalgam fillings with B-Hg. However, these correlations could only marginally explain regional differences. CONCLUSIONS: These mainly European results indicate that some children experience about doubled exposures to toxic elements just because of where they live. These exposures are unsafe, identifiable, and preventable and therefore call for preventive actions. Int J Occup Med Environ Health. 2023;36(3):349-64.

Association of Zn and Cu Levels in Cord Blood and Maternal Milk with Pregnancy Outcomes among the Slovenian Population.

Trace elements, including zinc (Zn) and copper (Cu), are known to play important roles in human health. The present study aimed to assess the levels of Zn and Cu in cord blood and maternal milk and to analyze their association with maternal and infant characteristics and pregnancy outcomes in a Slovenian study population of mothers and their neonates recruited within the PHIME prospective cohort study. The study included 324 mothers, but the data on Zn and Cu levels in both cord blood and maternal milk was available for 243 mothers. Questionnaires were used to assess the socio-demographic and health status of the mothers, their lifestyle habits (including detailed nutritional habits), and their residential and occupational histories. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure Zn and Cu levels in cord blood and maternal milk. Low Zn levels in cord blood were associated with lower gestational age and birth weight and were correlated with an increased probability of the birth of small for gestational age (SGA) infants. Maternal smoking influenced the Cu levels in both cord blood and maternal milk. Cord blood Cu levels were higher and Cu levels in maternal milk were lower in smoking compared to non-smoking mothers. Most importantly, a decreased Zn/Cu ratio in cord blood was associated with lower gestational age and lower birth weight. This indicates the overall positive effects of Zn and negative effects of Cu on pregnancy outcomes.

Suspect and non-targeted screening-based human biomonitoring identified 74 biomarkers of exposure in urine of Slovenian children.

Human exposure to organic contaminants is widespread. Many of these contaminants show adverse health effects on human population. Human biomonitoring (HBM) follows the levels and the distribution of biomarkers of exposure (BoE), but it is usually done in a targeted manner. Suspect and non-targeted screening (SS/NTS) tend to find BoE in an agnostic way, without preselection of compounds, and include finding evidence of exposure to predicted, unpredicted known and unknown chemicals. This study describes the application of high-resolution mass spectrometry (HRMS)-based SS/NTS workflow for revealing organic contaminants in urine of a cohort of 200 children from Slovenia, aged 6-9 years. The children originated from two regions, urban and rural, and the latter were sampled in two time periods, summer and winter. We tentatively identified 74 BoE at the confidence levels of 2 and 3. These BoE belong to several classes of pharmaceuticals, personal care products, plasticizers and plastic related products, volatile organic compounds, nicotine, caffeine and pesticides. The risk of three pesticides, atrazine, amitraz and diazinon is of particular concern since their use was limited in the EU. Among BoE we tentatively identified compounds that have not yet been monitored in HBM schemes and demonstrate limited exposure data, such as bisphenol G, polyethylene glycols and their ethers. Furthermore, 7 compounds with unknown use and sources of exposure were tentatively identified, either indicating the entry of new chemicals into the market, or their metabolites and transformation products. Interestingly, several BoE showed location and time dependency. Globally, this study presents high-throughput approach to SS/NTS for HBM. The results shed a light on the exposure of Slovenian children and raise questions on potential adverse health effects of such mixtures on this vulnerable population.

Maternal Blood Levels of Toxic and Essential Elements and Birth Outcomes in Argentina: The EMASAR Study.

Pregnant women's levels of toxic and essential minerals have been linked to birth outcomes yet have not been adequately investigated in South America. In Argentina, n = 696 maternal whole blood samples from Ushuaia (n = 198) and Salta (n = 498) were collected in 2011-2012 among singleton women at 36 ± 12 h postpartum and analyzed for blood concentrations of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), copper (Cu), manganese (Mn), selenium (Se) and zinc (Zn). This study examined the associations between maternal elements levels and birth outcomes, and sociodemographic factors contributing to elements levels. Maternal age, parity, body mass index, smoking, and education were linked to concentrations of some but not all elements. In adjusted models, one ln-unit increase in Pb levels was associated with increased gestational age (0.2 weeks, 95% CI = 0.01-0.48) and decreased birth weight (-88.90 g, 95% CI = -173.69 to -4.11) and birth length (-0.46 cm, 95% CI = -0.85 to -0.08) in the Salta sample. Toxic elements concentrations were not associated with birth outcomes in Ushuaia participants. Birth outcomes are multifactorial problems, and these findings provide a foundation for understanding how the body burden of toxic and essential elements, within the socioeconomic context, may influence birth outcomes.

Polycyclic aromatic hydrocarbons (PAHs) in men and lactating women in Slovenia: Results of the first national human biomonitoring.

In the first national human biomonitoring study in the Slovenian population of adults (18-49 years), including men (n = 297) and lactating primiparous women (n = 304), exposure to polycyclic aromatic hydrocarbons (PAHs) was evaluated. Nine urinary metabolites of four parent PAHs were determined. These included 1-hydroxypyrene (1-OHPYR), 2-hydroxynaphthalene (2-OHNAP), 2-hydroxyphenanthrene (2-OHPHE), 3-hydroxyphenanthrene (3-OHPHE), 4-hydroxyphenanthrene (4-OHPHE), a combination of 2-hydroxyfluorene and 3-hydroxyfluorene (2/3-OHFLU) and a combination of 1-hydroxyphenanthrene and 9-hydroxyphenanthrene (1/9-OHPHE). For comparison, the analysed phenanthrene metabolites were reported as a sum (ΣOHPHE = 1/9-OHPHE + 2-OHPHE + 3-OHPHE + 4-OHPHE) and all the analysed PAH metabolites were reported as a sum (ΣOHPAH = 1-OHPYR + 2/3-OHFLU + 2-OHNAP + ΣOHPHE). All metabolites or their combinations were determined in more than 91% of the samples, except 4-OHPHE, which was determined in only 5% of the samples. The highest concentration was found for 2-OHNAP. This was followed by 2/3-OHFLU and the phenanthrene metabolites, while the lowest concentration was determined for 1-OHPYR. Among the phenanthrene metabolites, the highest concentration was determined for 2-OHPHE, followed by 1/9-OHPHE and then by 3-OHPHE. Values in units of volume and values adjusted for specific gravity were significantly higher in men than in lactating primiparous women for all metabolites, whereas values in units adjusted for creatinine were generally higher in lactating primiparous women than in men. The difference between the two study groups, men and lactating primiparous women, was no longer significant in statistical models adjusted for specific gravity, suggesting that smoking, wood-burning exposure, and/or education largely explained the difference in PAH exposure in both study groups. For most metabolites, predictors of exposure were less significant in lactating primiparous women than in men. Also, site-specific patterns of exposure were observed, with additional predictors identified in certain areas, namely, proximity to roads and release of particulate matter (PM10) from industry. The time of year in which sampling took place appeared to be an important determinant in urban areas and in the case of participants who used wood for heating. Specific dietary factors could not be identified, as the study questionnaire did not include information on PAH-related diet. Despite the low number of paired partners (women and men living in the same household, n = 84), significant positive correlations for all metabolites were observed. This indicated that 31%-56% of variability in exposure could be explained by shared exposure to sources within the households (such as diet and wood-burning-related determinants).

Seasonal glyphosate and AMPA levels in urine of children and adolescents living in rural regions of Northeastern Slovenia.

There are extensive data on the toxicity of glyphosate (GLY) based herbicides (GBH), however the interpretation of some data (e.g. carcinogenic effect) are subject to controversy. For the appropriate health risk assessment more data on exposure levels in the general population, especially in susceptible groups such as pregnant women, the elderly and children are needed. The aims of the present study were to estimate the exposure to GLY and its major metabolite aminomethylphosphonic acid (AMPA) in children and adolescents living in agricultural areas, to identify possible determinants of the exposure, and to assess co-exposure with elements. In total, 149 children (aged 7-10 years, 55% girls) and 97 adolescents (aged 12-15 years; 44% girls) were recruited in 2018 from rural areas of Northeastern Slovenia. The effect of seasonal GLY application on the exposure was estimated using GLY and AMPA levels determined by GC-MS/MS in first morning urine in winter (n = 246) and in late-spring/early-summer seasons (n = 225). Levels of elements were determined by ICP-MS in urine in both samplings and in blood or plasma in the first sampling. Questionnaire data on basic characteristics, dietary habits, living environments and use of pesticides were obtained for all participants. GLY and AMPA were detected in 27% and 50% of urine samples from the first sampling period, respectively; and in 22% and 56% from the second sampling period, respectively. Geometric means and medians of both AMPA and GLY were below or at the limit of quantification (≤LOQ; 0.1 µg/L). Children rather than adolescents tended to have higher exposure, as did, boys rather than girls among adolescents. The exposure did not significantly differ between both sampling periods. Except for one individual, exposure was not higher among participants who reported use of GLY or herbicides in the vicinity of child's home or live in close vicinity of agriculture, orchards, vineyards, gardens, sport courts or cemeteries. The extensive food consumption frequency data revealed higher exposure to GLY and AMPA only among individuals with higher consumption of nuts and wholegrain rice. Levels of AMPA and GLY were significantly positively correlated, with considerably stronger correlation in urine of the second than the first sampling (Spearman's rank coefficient: 0.49 vs 0.22, respectively). Urine levels of As, Pb, Co, Zn and Cu were significantly higher in participants with GLY and/or AMPA levels ≥LOQ than with levels

Results of the first national human biomonitoring in Slovenia: Trace elements in men and lactating women, predictors of exposure and reference values.

The first national human biomonitoring in Slovenia surveyed cadmium (Cd), lead (Pb), mercury (Hg), arsenic (As), manganese (Mn), selenium (Se), copper (Cu) and zinc (Zn) in a childbearing population (18-49 years) selected from lactating primiparous women and men (N = 1084). The overall aim was to estimate trace elements' levels and geographical variations in order to identify sources of possible exposures and set the national reference values. The study population was selected evenly from 12 study areas across Slovenia, including rural, urban and known or potentially contaminated environments. Within 6-8 weeks after delivery, venous blood, spot urine, scalp hair and breast milk samples were collected to determine the selected elements. The data analysis included descriptive statistics and multiple linear regression using elemental concentrations in biological matrices, questionnaire data and environmental datasets. Essential elements showed no significant deficiencies or excessive levels in the study population and were largely determined by sex and/or the participating women's physiological status (postpartum, lactation), as well as by certain dietary sources. Toxic elements' levels were mainly below the levels considered to present increased health risk. Lifestyle and nutritional habits appeared as significant determinants of exposure to Cd (smoking and game meat consumption), Hg (seafood and amalgam fillings), As (seafood) and Pb (alcohol consumption, smoking, game meat consumption and type of water supply). A distinctive geographical pattern was confirmed, due to past mining activities combined with naturally elevated background levels in the cases of Pb (Mezica Valley), Hg (Idrija and Posocje) and As exposure (Zasavje). Increased seafood consumption in the coastal study area contributed to higher Hg and As (arsenobetaine) levels. Extensive sample size database accompanied with life-style and environmental data improved the prediction of exposure patterns, set the reference values for the childbearing population living in Slovenia, and provided a strong basis for evaluating spatial and temporal trends in exposure. To our best knowledge, this is the first study to establish reference values for lactating primiparous women.

Arsenic metabolites; selenium; and AS3MT, MTHFR, AQP4, AQP9, SELENOP, INMT, and MT2A polymorphisms in Croatian-Slovenian population from PHIME-CROME study.

The relationships between inorganic arsenic (iAs) metabolism, selenium (Se) status, and genetic polymorphisms of various genes, commonly studied in populations exposed to high levels of iAs from drinking water, were studied in a Croatian-Slovenian population from the wider PHIME-CROME project. Population consisted of 136 pregnant women in the 3rd trimester and 176 non-pregnant women with their children (n = 176, 8-9 years old). Their exposure to iAs, defined by As (speciation) analyses of biological samples, was low. The sums of biologically active metabolites (arsenite + arsenate + methylated As forms) for pregnant women, non-pregnant women, and children, respectively were: 3.23 (2.84-3.68), 1.83 (1.54-2.16) and 2.18 (1.86-2.54) ng/mLSG; GM (95 CI). Corresponding plasma Se levels were: 54.8 (52.8-56.9), 82.3 (80.4-84.0) and 65.8 (64.3-67.3) ng/mL; GM (95 CI). As methylation efficiency indexes confirmed the relationship between pregnancy/childhood and better methylation efficiency. Archived blood and/or saliva samples were used for single nucleotide polymorphism (SNP) genotyping of arsenic(3+) methyltransferase - AS3MT (rs7085104, rs3740400, rs3740393, rs3740390, rs11191439, rs10748835, rs1046778 and the corresponding AS3MT haplotype); methylene tetrahydrofolate reductase - MTHFR (rs1801131, rs1801133); aquaporin - AQP 4 and 9 (rs9951307 and rs2414539); selenoprotein P1 - SELENOP (rs7579, rs3877899); indolethylamine N-methyltransferase - INMT (rs6970396); and metallothionein 2A - MT2A (rs28366003). Associations of SNPs with As parameters and urine Se were determined through multiple regression analyses adjusted using appropriate confounders (blood As, plasma Se, ever smoking, etc.). SNPs' influence on As methylation, defined particularly by the secondary methylation index (SMI), confirmed the 'protective' role of minor alleles of six AS3MT SNPs and their haplotype only among non-pregnant women. Among the other investigated genes, the carriers of AQP9 (rs2414539) were associated with more efficient As methylation and higher urine concentration of As and Se among non-pregnant women; poorer methylation was observed for carriers of AQP4 (rs9951307) among pregnant women and SELENOP (rs7579) among non-pregnant women; MT2A (rs28366003) was associated with higher urine concentration of AsIII regardless of the pregnancy status; and INMT (rs6970396) was associated with higher As and Se concentration in non-pregnant women. Among confounders, the strongest influence was observed for plasma Se; it reduced urine AsIII concentration during pregnancy and increased secondary methylation index among non-pregnant women. In the present study of populations with low As exposure, we observed a few new As-gene associations (particularly with AQPs). More reliable interpretations will be possible after their confirmation in larger populations with higher As exposure levels.

Platinum, palladium, rhodium, molybdenum and strontium in blood of urban women in nine countries.

BACKGROUND: There is little reliable information on human exposure to the metals platinum (Pt), palladium (Pd) and rhodium (Rh), despite their use in enormous quantities in catalytic converters for automobile exhaust systems. OBJECTIVES: To evaluate blood concentrations of Pt (B-Pt), Pd (B-Pd) and Rh (B-Rh) in women from six European and three non-European countries, and to identify potentially influential factors. In addition, molybdenum (Mo) and strontium (Sr) were analysed. METHODS: Blood from 248 women aged 47-61 was analysed by high resolution inductively coupled plasma mass spectrometry under strict quality control. RESULTS: The medians were: B-Pt 0.8 (range <0.6-5.2), B-Pd <5 (<5-9.3), B-Rh <0.4 (<0.4-3.6)ng/L and B-Mo 2.0 (0.2-16) and B-Sr 16.6 (3.5-49) µg/L. Two women with highly elevated B-Pt (242 and 60ng/L), previously cancer treated with cis-platinum, were not included in the data analysis. All elements varied geographically (2-3 times) (B-Pd P=0.05; all other elements P<0.001); variations within each area were generally 5-10 times. Traffic was not associated with increased concentrations. CONCLUSIONS: General population blood concentrations of Pt, Pd and Rh are within or below the single digit ng/L range, much lower than in most previous reports. This is probably due to improved analytical performance, allowing for more reliable information at ultra-trace levels. In general, Mo and Sr agreed with previously reported concentrations. All elements showed geographical and inter-individual variations, but no convincing relationships with self-reported traffic intensity were found. Pt from the antineoplastic drug cis-platinum is retained in the body for years.

Low cadmium exposure in males and lactating females-estimation of biomarkers.

BACKGROUND: Urine cadmium (Cd) and renal function biomarkers, mostly analysed in urine spot samples, are well established biomarkers of occupational exposure. Their use and associations at low environmental level are common, but have recently been questioned, particularly in terms of physiological variability and normalisation bias in the case of urine spot samples. AIM: To determine the appropriateness of spot urine and/or blood Cd exposure biomarkers and their relationships with renal function biomarkers at low levels of exposure. To this end, we used data from Slovenian human biomonitoring program involving 1081 Slovenians (548 males, mean age 31 years; 533 lactating females, mean age 29 years; 2007-2015) who have not been exposed to Cd occupationally. RESULTS: Geometric means (GMs) of Cd in blood and spot urine samples were 0.27ng/mL (0.28 for males and 0.33 for females) and 0.19ng/mL (0.21 for males and 0.17 for females), respectively. Differing results were obtained when contrasting normalisation by urine creatinine with specific gravity. GMs of urine albumin (Alb), alpha-1-microglobulin (A1M), N-acetyl-beta-glucosaminidase (NAG), and immunoglobulin G (IgG) were far below their upper reference limits. Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses with unnormalised data were taken as more valid. Relatively weak positive associations were observed between urine Cd (ng/mL) and blood Cd (ß=0.11, p=0.002 for males and ß=0.33, p<0.001 for females) and for females between urine NAG and blood Cd (ß=0.14, p=0.04). No associations were found between other renal function biomarkers and blood Cd. Associations between Cd and renal function biomarkers in urine were stronger (p<0.05, ß=0.11-0.63). Mostly, all of the associations stayed significant but weakened after normalisation for diuresis. In the case of A1M, its associations with Cd were influenced by current smoking and blood Pb in males and by pre-pregnancy smoking and blood Se in females (ß up to 0.34, p<0.001). Statistical analysis of unnormalised or normalised urine data often yielded inconsistent and conflicting results (or trends), so association analyses data with unnormalised were taken as more valid. CONCLUSIONS: The observed uncertainties introduced by urine normalisation, particularly by creatinine, confirm blood Cd as a superior low-Cd exposure biomarker versus urine Cd in cases when 24h urine is unattainable. Evidence that A1M can be positively related to Cd, smoking (current or pre-pregnancy), Pb, and Se status, points to the versatile biological functions of A1M.

Arsenic, cadmium, lead and mercury levels in blood of Finnish adults and their relation to diet, lifestyle habits and sociodemographic variables.

The Northern Finland Birth Cohort program (NFBC) is the epidemiological and longitudinal prospective general population research program, which was established to promote health and wellbeing of the population in northern Finland. The aim of present study, as a part of the NFBC program, was to analyze the blood levels of arsenic (B-As), cadmium (B-Cd), lead (B-Pb), total mercury (B-Hg) and selenium (B-Se); to compare these levels with threshold limits; to study sociodemographic factors; and to correlate these levels with calcium and haemoglobin. The study was comprised of 249 NFBC subjects, of which 123 were female and 126 were male (ages 31.1 ± 0.3 and 31.1 ± 0.4, respectively). All participants were asked to complete a questionnaire regarding diet and living habits. The geometric means (± SD) of B-As were 0.49 ± 2.80 µg/l and 0.44 ± 2.72 µg/l; B-Cd were 0.18 ± 4.02 µg/l and 0.12 ± 3.21 µg/l; B-Pb were 17.0 ± 1.8 µg/l and 9.06 ± 2.20 µg/l; B-Hg were 2.18 ± 2.02 µg/l and 1.85 ± 1.78 µg/l; and B-Se were 106.0 ± 1.3 and 94.3 ± 1.3 µg/l in males and females, respectively. Among the subjects in the present analysis, 23 % of males and 17.1 % of females had B-As levels above the ATSDR normal human levels of B-As in unexposed individuals (1.0 µg/l). The B-Pb geometric mean (12.44 µg/l) was approximately one eighth the CDC toxicological cut-off point of 100 µg/l. Twenty-one individuals (8.4 %) exceeded a B-Hg level of 5.8 µg/l. Fifty-eight females (47 %) had a B-Hg higher than 2.0 µg/l, the German Federal Environmental Agency cut-off point for women (18-69 years) who consume fish at least three times/month; therefore, their babies could be at risk of adverse effects during development.

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.

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.

Cadmium, mercury and lead in the blood of urban women in Croatia, the Czech Republic, Poland, Slovakia, Slovenia, Sweden, China, Ecuador and Morocco.

OBJECTIVES: The aim of the study was to make an international comparison of blood levels of cadmium (B-Cd), lead (B-Pb) and mercury (B-Hg) of women in seven European, and three non-European cities, and to identify determinants. MATERIALS AND METHODS: About 50 women (age: 46-62) from each city were recruited (totally 480) in 2006-2009. Interview and questionnaire data were obtained. Blood samples were analysed in one laboratory to avoid interlaboratory variation. RESULTS: Between the European cities, the B-Pb and B-Cd results vary little (range of geometric means: 13.5-27.0 µg/l and 0.25-0.65 µg/l, respectively); the variation of B-Hg was larger (0.40-1.38 µg/l). Between the non-European cities the results for B-Pb, B-Cd and B-Hg were 19.2-68.0, 0.39-0.99 and 1.01-2.73 µg/l, respectively. Smoking was a statistically significant determinant for B-Cd, while fish and shellfish intakes contributed to B-Hg and B-Pb, amalgam fillings also contributed to B-Hg. CONCLUSIONS: The present results confirm the previous results from children; the exposure to lead and cadmium varies only little between different European cities suggesting that other factors than the living area are more important. The study also confirms the previous findings of higher cadmium and lead levels in some non-European cities. The geographical variation for mercury is significant.

Cell membrane integrity and internalization of ingested TiO(2) nanoparticles by digestive gland cells of a terrestrial isopod.

The present study was motivated by the paucity of reports on cellular internalization of ingested titanium dioxide (TiO(2)) nanoparticles (nano-TiO(2)). The model invertebrate (Porcellio scaber, Isopoda, Crustacea) was exposed to food dosed with nano-TiO(2) containing 100, 1,000, 3,000, or 5,000 µg nano-TiO(2) per gram of food. After 14 d of exposure, the amount of Ti in the entire body was analyzed by inductively coupled plasma-mass spectrometry, and elemental analyses of tissue cross sections were performed by particle induced X-ray emission. In addition, a series of toxicological markers including feeding parameters, weight change, and survival, as well as cytotoxic effects such as digestive gland cell membrane stability, were monitored. Internalization of ingested nano-TiO(2) by the isopod's digestive gland epithelial cells was shown to depend on cell membrane integrity. Cell membranes were found to be destabilized by TiO(2) particles, and at higher extracellular concentrations of nano-TiO(2), the nanoparticles were internalized.

Blood cadmium, mercury, and lead in children: an international comparison of cities in six European countries, and China, Ecuador, and Morocco.

Children's blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 µg/L) and B-Pb (14-20 µg/L), but larger for B-Hg (0.12-0.94 µg/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 µg/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city children's B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe.