Pig farming in Slovenia has a long tradition and is known for producing high-quality pork; however, almost two-thirds is imported, raising concerns about mislabelling. In addition to modern Slovenian breeds (MB), the Krškopolje pig (KP), the only preserved autochthonous pig breed in Slovenia, is highly valued for its high-quality, marbled meat, which is sold at a premium price. This study presents the first Slovenian pork database on stable isotope (δ2H, δ18O, δ13C, δ15N, δ34S) and elemental composition, comprising 148 samples: 107 authentic Slovenian pork samples (MB and KP), 22 foreign samples, and 19 samples labelled as Slovenian collected from supermarkets. We investigated the geographical origin of modern-breed pork and the breed authenticity of Krškopolje pig pork using DD-SIMCA class modelling. The established DD-SIMCA models showed high sensitivity (97 % and 96 %) and specificity (100 % and 89 %), respectively. When applied to commercial pork products labelled as Slovenian, 79 % of the samples exhibited isotopic and elemental profiles that differed from the authentic Slovenian reference class established in this study. These findings demonstrate the potential of combined isotope-elemental profiling coupled with DD-SIMCA modelling as a complementary tool for pork origin authentication and traceability verification. However, classification results indicate consistency with the reference class rather than legal origin status and should therefore be interpreted accordingly.
Based on toxicological evidence, human exposure to phthalates (PHs) and diisononylcyclohexane-1,2-dicarboxylate (DINCH) may contribute to adverse health effects, especially during vulnerable developmental stages. To support the exposure assessment for this group of endocrine disruptors, we developed and validated a method for the analysis of 14 PH and 3 DINCH metabolites in human urine and maternal milk, applied the method in a pilot study, and identified crucial obstacles in the path of establishing maternal milk as a routine matrix in human biomonitoring. Urine and milk samples were extracted with solid-phase extraction (SPE) and QuEChERS salts, respectively, and analysed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). The method accuracy was confirmed for urine samples via a certified standard reference material and the G-EQUAS intercomparison programme. We identified a need for sampling protocols, reference materials, and external method verification schemes in order to establish maternal milk as a routine matrix. Finally, the method was tested for its applicability in a pilot biomonitoring study on 30 paired urine and milk samples from lactating mothers, with medians ranging from <LLOQ - 15 µg/L in urine and <LLOQ - 16 µg/L in maternal milk and generally higher detection rates in urine. Furthermore, the results indicate extensive monoester formation under cooled storage conditions, resulting in potentially high infantile exposure to phthalate monoesters for which, to date, no guidance values exist despite their demonstrated toxicity.
This study analysed urinary mercury (U-Hg) concentrations in 1412 Slovenian children across four human biomonitoring campaigns conducted between 2007 and 2024. Median U-Hg levels declined from 0.76 ng mL−1 (0.72 µg g−1 creatinine) in the 2007 PHIME cohort to 0.22 ng mL−1 (0.21 µg g−1 creatinine) in the 2018–2024 SLO-HBM-II cohort, paralleling a decrease in the prevalence (from 65 to 3
Monitoring toxic elements has a long tradition in Slovenia due to historical mining. More recently, attention has shifted to essential elements, since both deficiencies and excesses can harm health. Regular monitoring of (non-)essential elements supports risk assessment and policymaking. While urine and blood are common biomonitoring matrices, hair offers a non-invasive alternative that reflects exposure over several months, though standardised methodologies for hair analysis remain limited. This study aimed to develop and validate a sensitive and robust analytical method for the determination of 29 elements in human hair, addressing key challenges in sample preparation and contamination control. We developed a sensitive and robust method for the determination of 29 elements (Ag, Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, S, Sb, Se, Sn, Sr, Ti, U, V, and Zn) in 3 cm segments of human hair that involves a washing procedure with acetone and Milli-Q water, microwave digestion with 65% HNO3, and analysis with Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (ICP-MS/MS). Evaluation of preparation steps revealed stainless-steel scissors as a major contamination source. Glass digestion vessels were unsuitable for several elements due to high detection limits and relative standard deviations. The optimised method reduced analytical variability and improved sensitivity compared to published protocols. This validated method enables reproducible multi-elemental analysis in hair, highlights overlooked contamination risks, and is now applied in human biomonitoring studies to strengthen exposure assessment and standardisation efforts.
Endocrine-disrupting chemicals (EDCs), including known and unknown parent compounds, their metabolites, and transformation products, are pervasive in daily life, posing increasing risks to human health and the environment. This study employed a high-resolution mass spectrometry-based nontargeted screening approach, integrating polar (HILIC) and reversed-phase separations to expand the chemical space coverage and, supported by open-science tools and resources, evaluated urinary chemical profiles to assess internal EDC exposure. Among 106 annotated biomarkers of exposure, six exhibited significantly higher normalized intensities in patients with ovarian malignancies compared to healthy controls (p < 0.05). This suggests their greater exposure to phthalates (diethylhexyl phthalate and diethyl phthalate), pesticides (metolachlor metabolite and 4-nitrophenol), a UV filter (benzophenone-1), and an industrial byproduct (4-methyl-2-nitrophenol). These compounds may interfere with hormonal regulation, potentially contributing to cancer development. While these findings highlight potential differences in internal EDC exposure, the study primarily demonstrates the applicability of nontargeted urinary profiling for chemical exposure assessment. By providing new insights into EDCs burden and its pathological implications, this work contributes to advancing next-generation chemical risk assessment within the European Partnership for the Assessment of Risks from Chemicals initiative and supports the development of preventive strategies to mitigate environmental cancer risks.
Objectives: There are still limited or lacking data on the association of trace elements (TEs) with polycystic ovary syndrome (PCOS). This case–control study aimed to determine levels of essential TEs (manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo)) and non-essential TEs (arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb)) in urine, whole blood, and serum to investigate a possible association with kidney and liver function, endocrine and metabolic parameters, and environmental and lifestyle sources of potential exposure and provide possible recommendations. Methods: In our case–control study, women with PCOS (n = 35) and healthy controls (n = 35) underwent clinical and ultrasonographic examination, filled in questionnaires targeting general, lifestyle, and environmental information, and provided fasting venous blood samples and first morning urine for biochemical, hormonal, and TE analysis. Multiple linear regression models were used to evaluate the association between TE levels and data obtained through questionnaires. Results: In women with PCOS, lower Mo levels in whole blood (p = 0.024) and serum (p = 0.011) and higher serum Cu levels (p = 0.026) were detected when compared to healthy controls. Results of this study show that amendments in Cu and Mo levels might be related to altered kidney and liver function and disrupted hormonal balance in PCOS women. Cu levels positively correlated with leukocyte count. There was a negative correlation of Mo levels with proteinuria and luteinizing hormone levels. Regarding liver function, Mo negatively correlated with urinary bilirubin levels, and there was a positive association with alanine and aspartate aminotransferase, respectively. Dietary supplement consumption and certain diet habits appeared to be important predictors of exposure to Cu (beef consumption) or Mo (cereal and boiled vegetable consumption) and modify Mo and Cu levels in women. Conclusions: Concentrations of the chemical elements Mo and Cu in biological samples of women appear to be related to PCOS and nutrition. To our knowledge, this is a novel finding for Mo. Additional research is needed to provide more insights into the causality of the PCOS relationship with Mo and Cu in humans.
Premature ovarian insufficiency (POI) is poorly understood, with causes identified in only 25% of cases. Emerging evidence suggests links between trace elements (TEs) and POI. This study is the first to compare concentrations of manganese (Mn), copper (Cu), zinc (Zn), selenium (Se), molybdenum (Mo), arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) across urine, serum, and whole blood in women with POI compared to healthy controls (HC), aiming to explore their distribution and potential associations with POI. This cross-sectional-case-control study enrolled 81 participants (40 POI patients and 41 healthy controls) at the University Medical Centre Ljubljana, Slovenia. Blood and urine samples were collected to quantify basic biochemical parameters using standard clinical chemistry methods and concentrations of Mn, Cu, Zn, Se, Mo, As, Cd, Hg, and Pb using inductively coupled plasma-mass spectrometry (ICP-MS). Participants also completed questionnaires on socio-demographics, medical history, lifestyle, and nutrition. Data was analyzed using the Mann-Whitney U test, Student's t-tests, Fisher exact test, logistic regression models adjusted on body mass index (BMI), age, hematocrit, and Kendall's tau correlation. Women with POI had significantly higher BMI and red blood cell (RBC) indices, including hemoglobin, hematocrit, and red cell distribution width (RDW), compared to controls. A larger proportion of POI patients resided in rural agricultural areas. Liver and kidney function assessments showed no significant differences between the groups. Adjusted models revealed that POI patients had significantly lower urinary levels of Cu, Zn, Se, Mo, Cd, Hg, and Pb than controls, while whole blood Mn levels were higher. Serum Cu levels were significantly elevated in POI patients, whereas Pb, Cd, and Hg were lower. No significant differences were observed for As. Correlation analysis showed several strong to moderate associations among TEs across biofluids, but only weak correlations were found between TEs and demographic or biochemical factors. This study suggests potential associations between TEs and POI in women. Notably, most TEs (Zn, Se, Cu, Mo, Cd, Hg, Pb) were significantly lower in the urine of the POI group, while Cu, Cd, Hg, and Pb showed significant differences in both urine and serum.
Four jellyfish species, ctenophoran Mnemiopsis leidyi and scyphozoan Cotylorhiza tuberculata, Chrysoara hysoscella and Rhizostoma pulmo were collected in summer of 2017 in the Gulf of Trieste (northern Adriatic Sea) and analysed for Hg and other metal(loid)s to assess their bioaccumulation and biomonitoring potential. No significant differences in Hg levels (0.06-0.22 µg/g dry mass) were observed between the studied species but all significantly concentrated Hg well above the dissolved Hg seawater levels (5 ng/L) of the gulf. The studied species have diverse diets consisting primarily of various plankton groups. C. hysoscella feeds mainly on mesozooplankton (>200 µm) R. pulmo and C. tuberculata mostly consume microzooplankton (50-200 µm) while M. leidyi preys on various organism (and particles) in the water column. In addition, C. tuberculata harbours autotrophic endosymbionts (microalgae). Considering their feeding behaviour, it appears that studied jellyfish species do not bioaccumulate Hg, nor other metal(loid)s, along the pelagic food web. Hence, the Hg levels in jellyfish are probably the consequence of the dissolved metal (passive and active) uptake. Moreover, the methodological approach analysing the jellyfish freeze-dried samples containing salt can distort the real picture and the Hg/Corg. ratio could better describe the metal level in the gelatinous organism. However, considering the high Hg bioconcentration factor (log BCF >5), jellyfish can be used aa a useful bioindicator for Hg, and other metal(loid)s, dissolved in seawater. Keywords: Jellyfish, coastal waters, mercury, bioconcentration, contamination, bioindicator
[This corrects the article DOI: 10.1016/j.fochx.2025.103196.].
Saffron (Crocus sativus L.) is among the world's most valuable spices, yet its high market price and complex supply chains make it particularly vulnerable to mislabeling and fraud. To address this, we integrated stable isotope ratio analysis (δ 2H, δ 13C, δ 15N, δ 18O, δ 34S) with multi-elemental profiling and advanced statistical modeling to authenticate saffron geographical origin. A total of 75 saffron samples-48 authentic-sourced from Morocco, Greece, Slovenia, Spain, Iran, and the United Kingdom were analyzed using isotope ratio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICP-MS). These were combined with two previously published datasets, including 163 authentic samples in total. The incorporation of external datasets was possible due to their strong methodological and analytical comparability with the present study, ensuring directly compatible results. Orthogonal partial least squares discriminant analysis (OPLS-DA) achieved 94 % classification accuracy, identifying δ 2H, δ 15N, K, Ca, δ 13C, Sr, Mn, Co, and Zn as key variables for discriminating geographical origins. Incorporation of elemental ratios (Rb/Sr, K/Rb, Ca/Sr) and/or δ 18O and δ 34S further refined classification, particularly improving accuracy for Moroccan saffron. Class-modeling via Data-Driven Soft Independent Modeling of Class Analogy (DD-SIMCA) confirmed high sensitivity and specificity across target sets and revealed potential mislabeling in ∼15 % of commercial samples, with the highest discrepancy (24 %) observed in Iranian-labeled products. These findings underscore the power of combined stable isotope and multi-elemental approaches for saffron origin authentication and highlight the need for robust analytical verification to strengthen transparency and combat fraud in the saffron trade.
The Exposure and Health Examination Survey (EXHES) cohort aims to elucidate the impact of environmental exposures (the external exposome) and their biological markers (the internal exposome) on childhood health conditions, asthma and allergies, obesity, and cognitive development in particular. Utilizing singletons and twins helped differentiate environmental effects from genetic influences due to the shared genetic background in twins. The EXHES cohort includes 2356 mother-child pairs across 10 European countries, comprising 1945 singletons and 411 twins, with data collected during the crucial first 1000 days of life. Data were gathered through epidemiological questionnaires and biomarkers, including blood, urine, hair, and breast milk from mothers, and cord blood, placenta, and cord tissues from children. Findings confirm that twin pregnancies are linked with increased risks of pregnancy complications, preterm birth, cesarean delivery, low birthweight, maternal health problems during pregnancy and a lower risk of macrosomia. Moreover, mothers of twins were more likely to have asthma, while higher maternal education was associated with a lower likelihood of twin births. The EXHES cohort provides a robust framework to be adopted in other studies for comparing singletons and twins to better understand how the exposome affects early child development and health outcomes. This approach offers new insights into the interplay between environmental and biological factors in shaping long-term health.
OBJECTIVES:Aidarken is a region with mercury production from cinnabar and, to a lesser extent, from mercury-antimony-fluorite and waste recycling. Recent smelting emissions of elemental Hg vapour are low; however, combined with past pollution legacies, anaemia and iodine deficiency, the health effects for vulnerable populations are still possible. The study aimed to evaluate metal(loid)s status in Aidarken pregnant women vs those from an Hg-noncontaminated region. METHODS:90 pregnant women (3rd trimester) aged 19-39 years were recruited into the cross-sectional study: Aidarken (n = 55) and Hg-uncontaminated Kara-Suu (n = 35) region. The fasting blood samples were analysed for 22 metal(loid)s by ICP-MS and haemoglobin. The difference in metal(loid) levels between the groups (and within groups according to the presence of goitre) was estimated by multiple variable linear regression models. RESULTS:Metal(loid) blood levels were within reference ranges. We estimated the statistical significance of between-group differences for several metal(loid)s. Essential S, P, Fe, Ca, Mg, Co and Se and non-essential Hg, U, As, Cs and Rb were higher in the exposed than in the control group. On the contrary, the essential Na and Cu, and nonessential Sr and Ba were lower in the exposed vs controls. Mean haemoglobin levels didn't differ between the groups, while the incidence of goitre was higher in the exposed group (34.6 % vs 11.4 %). In the exposed group, the presence of goitre was estimated as a possible predictor for higher levels of Hg, Rb, Mn, Fe and Se. CONCLUSIONS:We found no critical Hg-related health concern for Aidarken pregnant women. The nutritional status of some essential metal(loid)s was even better in the exposed than in the control group. However, the results may indicate that long-term chronic exposure to moderate Hg levels could worsen thyroid health issues in a given environmental (iodine-deficient region) and lifestyle (suboptimal use of iodinated salt) conditions.
Prenatal lead (Pb) and manganese (Mn) exposure can impair neurodevelopment, targeting the central nervous system. This study investigated the effects of prenatal exposure to Pb and Mn on neurodevelopment in children at 18 months of age, using data from 607 Italian mother–child pairs enrolled in the Northern Adriatic Cohort II (NAC-II). All children born at term (≥37 weeks) were assessed with the Bayley Scales of Infant and Toddler Development, third edition. Cord blood concentrations of Mn and Pb were categorized as low or high exposures based on the 75th percentile of their distribution. Sociodemographic and lifestyle information was collected via questionnaires. Using simple and multiple linear regressions, the study examined the relationship between the cognitive composite score (COGN) and Mn and Pb co-exposure, including their interaction. Stratified regressions explored how Mn exposure influenced the effect of Pb, in the whole cohort and by the child’s sex. Beta coefficients (β) and the 90% confidence interval (90% CI) were estimated. Boys showed an interaction effect between Mn and Pb, with a reduction in COGN (β = −5.78, 90% CI: −11.17; −0.40), further described as a negative effect of high Pb on cognition when Mn exposure was also high (β = −6.98, 90% CI: −10.93; −3.04). No clear effects were observed in girls or the entire cohort at these levels of exposure. The findings highlight the harmful impact of combined prenatal Pb and Mn exposure on cognitive development in boys.
The genetic susceptibility to low-level lead (Pb) exposure in general populations has been poorly investigated and is limited to the single nucleotide polymorphism (SNP) rs1800435 in the delta-aminolevulinic acid dehydratase gene (ALAD). This study explored associations between ten selected ALAD SNPs with Pb concentrations in blood (BPb) and urine (UPb) among 281 men aged 18-49 years from Slovenia, including 20 individuals residing in a Pb-contaminated area. The geometric mean (range) of BPb and UPb were 19.6 (3.86-84.7) μg/L and 0.69 (0.09-3.82) μg/L SG, respectively. The possible genetic influence was assessed by examining SNP haplotypes, individual SNPs, and the combination of two SNPs using multiple linear regression analyses. While no significant associations were found for haplotypes, the presence of variant alleles of rs1800435 and rs1805312 resulted in an 11% and 13% decrease in BPb, respectively, while the presence of variant allele of rs1139488 (homozygous only) exhibited significant 20% increase in BPb, respectively. Additionally, variant allele of rs1800435 resulted in lower UPb. Individual SNPs in the model explained only around 1 additional percentage point of BPb variability. In contrast, combination analyses identified six combinations of two SNPs, which significantly explained 3-22 additional percentage points of BPb variability, with the highest explanatory power observed for the rs1800435-rs1139488 and rs1139488-rs1805313 combinations. Moreover, excluding participants from the Pb-contaminated area indicated that exposure level influenced SNPs-Pb associations. Our results confirm the importance of the ALAD gene in Pb kinetics even at low exposure levels. Additionally, we demonstrated that identifying individuals with specific combinations of ALAD SNPs explained a larger part of Pb variability, suggesting that these combinations, pending confirmation in other populations and further evaluation through mechanistic studies, may serve as superior susceptibility biomarker in Pb exposure compared to individual SNPs.
Main text Seafood is one of the major food resources for human consumption in the world. The CODEX Alimentarius Commission and many jurisdictions have set maximum levels of metallic contaminants in seafood. The use of reliable methods for measurement of metallic contaminants is important in safeguarding the quality of these products and public health. The Supplementary Comparison APMP.QM-S19: Toxic Elements in Seafood was coordinated by the Government Laboratory, Hong Kong, China (GLHK). Four measurands (arsenic, cadmium, mercury and lead) in seafood were chosen. The last CCQM or RMO key comparison / supplementary comparison in the area of metallic contaminants in seafood was organized by GLHK in 2011 (APMP.QM-S5). Hence, it was timely to organize another comparison that covers different measurands. This Supplementary Comparison (APMP.QM-S19) offers different analytical challenges (e.g. in analysis of mercury and a different range of measurands) as compared to the previous comparison. Moreover, it enabled National Metrology Institutes / Designated Institutes (NMIs/DIs) that did not participate in the previous comparisons to demonstrate their measurement competencies. Nineteen institutes participated in APMP.QM-S19. Most participating NMIs/DIs employed microwave-assisted acid digestion for sample dissolution. Inductively coupled plasma mass spectrometry (ICP-MS), including triple quadrupole and sector field, were the most commonly used instrumental techniques. Results of all participating NMIs/DIs were evaluated against the supplementary comparison reference value (SCRV). The SCRV and associated uncertainty were determined from results of NMIs/DIs that participated in the supplementary comparison using methods with demonstrated metrological traceability. Median was used as estimator of the SCRVs. For arsenic, the SCRV was 1.342 mg/kg calculated from 15 participating NMIs/DIs. For arsenic, cadmium, mercury and lead, the SCRVs were 1.342 mg/kg, 0.3630 mg/kg, 0.1230 mg/kg and 0.4101 mg/kg, respectively, calculated from 15, 14, 13 and 11 participating NMIs/DIs. Participating NMIs/DIs that have successfully participated in APMP.QM-S19 have demonstrated measurement capabilities in determining inorganic elements, in a mass fraction range from 0.02 mg/kg to 50 mg/kg in high organic content matrix, including seafood of animal origin and high protein food. To reach the main text of this paper, click on Final Report . Note that this text is that which appears in Appendix B of the BIPM key comparison database https://www.bipm.org/kcdb/ . The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Lead (Pb) is a global contaminant associated with multiple adverse health effects. Humans are especially vulnerable during critical developmental stages. During pregnancy, exposure to Pb can occur through diet and release from maternal bones. Apolipoprotein E gene (APOE) variants (ɛ2, ɛ3, ɛ4 alleles) may influence sex steroid hormones, bone metabolism, and Pb kinetics.We examined the interplay among maternal APOE (mAPOE) genotypes, fetal sex, parity, and Pb in maternal and cord blood (mB-Pb, CB-Pb) using linear regression models. Our study involved 817 pregnant women and 772 newborns with measured adequate levels of zinc and selenium. We compared carriers of the ε2 and ε4 alleles to those with the ε3/ε3 genotype.The geometric means (range) of mB-Pb and CB-Pb were 11.1 (3.58–87.6) and 9.31 (1.82–47.0) ng/g, respectively. In cases with female fetuses, the maternal mAPOE ε2 allele was associated with higher, while the mAPOE ε4 allele was associated with lower mB-Pb and CB-Pb levels. Nulliparity increased the strength of the observed associations. These findings highlight the significance of mAPOE genetics, fetal sex, and parity in prenatal Pb kinetics. Notably, the maternal ε2 allele may increase the risk of Pb exposure.
Background: There is almost no data on the combined associations between apolipoprotein E gene (APOE) genotypes, trace elements (TEs), and lipid peroxidation in vivo. The aim of our study was to evaluate the association between APOE genotypes and TE levels in blood (B-TEs) and erythrocytes (E-TEs), and 8-isoprostane in urine (U8-isoprostane) in women with low exposure to potentially toxic TEs and with adequate supply of essential TEs. Methods: B-TEs, E-TEs and U-8-isoprostane were determined in 172 healthy women of childbearing age (30.1-51.4 years) using ICP-MS and ELISA competitive assay, respectively. All women were divided into three APOE genotype groups according to the presence of the e4 allele, e2 allele or e3 homozygotic allele. The associations between B-TEs, E-TE, U-8-isoprostane, and the APOE genotype groups were estimated by multiple variable linear regression models with relevant explanatory variables (e.g., age, BMI, and seafood). Results: All TE and U-8-isoprostane levels were inside the reference ranges for the healthy population. In the multiple variable linear regression models, our results showed that urine 8-isoprostane levels increased by up to 43.3% in the APOE4 group compared to the APOE3 group and a negligible negative modifying effect for essential TEs. However, the APOE genotype groups were associated also with some TEs. A clear positive association was found between the APOE2 and APOE4 groups (vs. APOE3) with B-molybdenum. Conclusions: Our study suggests that the APOE4 genotype played an important role in 8-isoprostane variability in a population with an adequate supply of essential and with low exposure to potentially toxic TEs. Adequate copper, zinc and selenium status seemed to be protective against, while the levels of nonessential TEs were probably too low to play a decisive role in 8-isoprostane formation. The observed impact of the APOE2 and APOE4 groups on increased B-molybdenum opens a new research topic.
Background Trace elements, including zinc (Zn) and copper (Cu), although toxic at higher concentrations are known to play important roles in the maintenance of human health and neurodevelopment. Few epidemiological studies have investigated the association between prenatal or early postnatal Cu and Zn levels and child neurodevelopment. The aim of this research is to assess the association between child neurodevelopment at 18 months of age and cord blood and breast milk concentrations of Cu and Zn in Italian mother-child pairs enrolled in the Italian Northern Adriatic Cohort II (NAC-II), a part of the “Public health impact of long-term, low-level, mixed element exposure in susceptible population strata” project PHIME. Methods The study population consisted of 632 children, and their mothers, born within the NAC-II, who were tested with the Bayley Scales of Infant and Toddler Development third edition (BSID-III) at age 18 months. Cu and Zn concentrations were measured in cord blood and breast milk samples. Only children born at term (≥37 gestational week), who completed the BSID-III test and had at least 1 measure of Cu and Zn concentrations were included in the analysis. Information about socio-demographics and lifestyles were collected through questionnaires at different phases of follow-up. Cu and Zn concentrations were log2 transformed because of their skewed distribution. Multiple linear regression models were performed to study the association between each BSID-III composite score (cognitive, motor and language) and each metal concentration. Separate models were applied for each biological sample. The β coefficient (β) and its 95% confidence interval (95% CI) were estimated. Stratified analyses by child's sex were also conducted. Results The mean ± standard deviation (SD) of cognitive, motor and language composite scores were respectively: 106 ± 8, 101 ± 5 and 97 ± 8. The mean ± SD of Cu and Zn concentrations (ng/g) were respectively 699.2 ± 129.0 and 2538 ± 589 in cord blood and 607 ± 498 and 3226 ± 1428 in breast milk. No association between metal concentration and cognitive composite score was found. A higher motor composite score was associated with higher Cu concentrations in cord blood (β = 4.31 95% CI 2.03; 6.59). No associations were found between language composite score and metal concentrations. The effect of Cu cord blood concentration on motor composite score was confirmed when stratified by sex: males (β = 5.49 95% CI 2.15; 8.36) and females (β = 3.11; 95% CI 0.00; 6.22). A direct association, in females only, was found between language composite score and Cu concentration in cord blood (β = 5.60 95% CI 0.63; 10.57) and in breast milk (β = 3.04 95% CI 1.06; 5.03), respectively. Conclusion The results from this cohort study showed a strong direct association between prenatal Cu levels and child motor neurodevelopment at 18 months. However, for generalizability, future research on the effects of Zn and Cu on neurodevelopment should include a larger range of early-life concentration of trace elements.
Over 90 percent of the world's rice is produced and consumed in the Asia-Pacific region. Varieties such as Thai Jasmine rice and Paw San (or "Myanmar pearl rice") are globally recognised as premium, while more local high-grade varieties include the Indonesian Ciherang and Inpari. Being able to trace the origin of these products has become necessary, since they are marketed at relatively higher prices compared to other cultivars, and they often become the target of fraudulent activities. In this work, we aimed to identify variables that could distinguish the premium-producing regions within each country, by Isotope Ratio Mass Spectrometry (IRMS) and Inductively Coupled Plasma- Mass Spectrometry (ICP-MS). Low-Level Data Fusion (LLDF) followed the analysis of more than 300 authentic samples, and (O)PLS-DA models yielded very high accuracy values. The most important geo-differentiating variables (VIP>1.4) were identified as: delta C-13, delta O-18, delta H-2, delta S-34, Co, Rb, Cu, Ba and Zn.
Phthalates are mainly used as plasticizers for polyvinyl chloride (PVC). Exposure to several phthalates is associated with different adverse effects most prominently on the development of reproductive functions. The HBM4EU Aligned Studies (2014-2021) have investigated current European exposure to ten phthalates (DEP, BBzP, DiBP, DnBP, DCHP, DnPeP, DEHP, DiNP, DiDP, DnOP) and the substitute DINCH to answer the open policy relevant questions which were defined by HBM4EU partner countries and EU institutions as the starting point of the programme. The exposure dataset includes similar to 5,600 children (6-11 years) and adolescents (12-18 years) from up to 12 countries per age group and covering the North, East, South and West European regions. Study data from participating studies were harmonised with respect to sample size and selection of participants, selection of biomarkers, and quality and comparability of analytical results to provide a comparable perspective of European exposure. Phthalate and DINCH exposure were deduced from urinary excretions of metabolites, where concentrations were expressed as their key descriptor geometric mean (GM) and 95th percentile (P95). This study aims at reporting current exposure levels and differences in these between European studies and regions, as well as comparisons to human biomonitoring guidance values (HBM-GVs). GMs for children were highest for Sigma DEHP metabolites (33.6 mu g/L), MiBP (26.6 mu g/L), and MEP (24.4 mu g/L) and lowest for Sigma DiDP metabolites (1.91 mu g/L) and Sigma DINCH metabolites (3.57 mu g/L). In adolescents highest GMs were found for MEP (43.3 mu g/L), Sigma DEHP metabolites (28.8 mu g/L), and MiBP (25.6 mu g/L) and lowest for Sigma DiDP metabolites (= 2.02 mu g/L) and Sigma DINCH metabolites (2.51 mu g/L). In addition, GMs and P95 stratified by European region, sex, household education level, and degree of urbanization are presented. Differences in average biomarker concentrations between sampling sites (data collections) ranged from factor 2 to 9. Compared to the European average, children in the sampling sites OCC (Denmark), InAirQ (Hungary), and SPECIMEn (The Netherlands) had the lowest concentrations across all metabolites and ESTEBAN (France), NAC II (Italy), and CROME (Greece) the highest. For adolescents, comparably higher metabolite concentrations were found in NEB II (Norway), PCB cohort (Slovakia), and ESTEBAN (France), and lower concentrations in POLAES (Poland), FLEHS IV (Belgium), and GerES V-sub (Germany). Multivariate analyses (Survey Generalized Linear Models) indicate compound-specific differences in average metabolite concentrations between the four European regions. Comparison of individual levels with HBM-GVs revealed highest rates of exceedances for DnBP and DiBP, with up to 3 and 5%, respectively, in children and adolescents. No exceedances were observed for DEP and DINCH. With our results we provide current, detailed, and comparable data on exposure to phthalates in children and - for the first time - in adolescents, and - for the first time - on DINCH in children and adolescents of all four regions of Europe which are particularly suited to inform exposure and risk assessment and answer open policy relevant questions.