Socio-demographic inequalities influence differences in the chemical exposome among Swedish adolescents.

Relatively little is known about the relationship between socio-demographic factors and the chemical exposome in adolescent populations. This knowledge gap hampers global efforts to meet certain UN sustainability goals. The present work addresses this problem in Swedish adolescents by discerning patterns within the chemical exposome and identify demographic groups susceptible to heightened exposures. Enlisting the Riksmaten Adolescents 2016-17 (RMA) study population (N = 1082) in human-biomonitoring, and using proportional odds ordinal logistic regression models, we examined the associations between concentrations of a diverse array of substances (N = 63) with the determinants: gender, age, participant/maternal birth country income per capita level, parental education levels, and geographic place of living (longitude/latitude). Participant/maternal birth country exhibited a significant association with the concentrations of 46 substances, followed by gender (N = 41), and longitude (N = 37). Notably, individuals born in high-income countries by high-income country mothers demonstrated substantially higher estimated adjusted means (EAM) concentrations of polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs) and per- and polyfluoroalkyl substances (PFASs) compared to those born in low-income countries by low-income country mothers. A reverse trend was observed for cobalt (Co), cadmium (Cd), lead (Pb), aluminium (Al), chlorinated pesticides, and phthalate metabolites. Males exhibited higher EAM concentrations of chromium (Cr), mercury (Hg), Pb, PCBs, chlorinated pesticides, BFRs and PFASs than females. In contrast, females displayed higher EAM concentrations of Mn, Co, Cd and metabolites of phthalates and phosphorous flame retardants, and phenolic substances. Geographical disparities, indicative of north-to-south or west-to-east substance concentrations gradients, were identified in Sweden. Only a limited number of lifestyle, physiological and dietary factors were identified as possible drivers of demographic inequalities for specific substances. This research underscores birth country, gender, and geographical disparities as contributors to exposure differences among Swedish adolescents. Identifying underlying drivers is crucial to addressing societal inequalities associated with chemical exposure and aligning with UN sustainability goals.

Lead, cadmium, and mercury blood levels in schoolchildren in southern Sweden: Time trends over the last decades.

To prevent diseases arising from exposure to toxic metals, more knowledge about their temporal changes is needed, especially in children, the most vulnerable group. This study follows temporal changes in blood lead (BPb), mercury (BHg) and cadmium (BCd) levels in schoolchildren (8-11 years old) from two cities in southern Sweden. One blood sample per 773 children was used for time trend analyses between 2007 and 2022. One further blood sample re-sampled after 2 years, were used to assess intra-individual time trends of BPb (n = 377), BCd (n = 102) and BHg (n = 53) between 1979 and 2019. Geometric mean (range) of BPb, BCd and BHg concentrations during 2007-2022 was 9.9 (2.3-59), 0.09 (0.03-0.34) and 0.73 (0.02-8.2) µg/L, respectively. Living close to a Pb smelter resulted in higher levels of all three metals compared with living in the city or rural area. Annually, the concentrations clearly decreased for BPb (-4.9%, p < 0.001) and weakly for BCd (-0.6%, p = 0.013), while BHg slightly increased (+1.4%, p = 0.029). When stratified by residential area, the decrease of BCd and increase of BHg were significant only in the urban area (-1.8% and +2.8%, respectively; p < 0.01). The BPb decrease rate was the highest in the urban area followed by the rural and Pb smelter areas (-5.8% > -4.5% > -3.9%; p < 0.001). For children re-analysed during 1979-2019, a significant decrease was observed only for BPb (-6.8%; p < 0.001), with a 2% higher decrease rate in the period before than after the Pb-gasoline ban in 1994. The preventive measures against Pb pollution are reflected in the constant decrease of BPb levels over time. However, the area close to a Pb smelter, as indicated by a slower Pb decrease rate, might need further and stricter preventive measures. Exposure to Hg and Cd was low, however, the slight increase in BHg and only a minor decrease in BCd, indicate the need for continuous biomonitoring of children.

Assessing the carcinogenic and non-carcinogenic health risks of metals in the drinking water of Isfahan, Iran.

Metals are significant contributors to water pollution, posing serious threats to human health. This study aims to assess the carcinogenic and non-carcinogenic health risks associated with metals in Isfahan drinking water. Eighty water samples were randomly collected from the city's distribution network between January and March 2020-2021. Inductively coupled plasma Optical Emission Spectrometry was used to measure toxic metals, namely Pb, Cr, Cd, Ni, and As concentrations. Results revealed that the mean concentration of Ni (70.03 µg/L) exceeded the WHO reference value (70 µg/L), while the other metals were below the standard values. The average chronic daily intake order of toxic metals was Ni > Cr > Pb > As > Cd. Non-carcinogenic risk assessment through hazard quotient (HQ) and hazard index (HI) demonstrated that both THI for adults (HQingestion + HQdermal = 4.02E-03) and THI for children (HIingestion + HIdermal = 3.83E-03) were below the acceptable limit (less than 1). This indicated no non-carcinogenic risk to residents through water ingestion or dermal exposure. However, findings indicated that the ingestion route was the primary exposure pathway, with HQ values for ingestion exceeding HQ values for dermal adsorption. Carcinogenic risk assessment showed that the risk associated with As metal exceeded the acceptable limit (1 × 10-6). Therefore, implementing treatment improvement programs and appropriate control measures is essential to safeguard the health of Isfahan City residents.

Low-level exposure to lead and atherosclerosis in the carotid arteries: Results from the Swedish population-based cohort SCAPIS.

BACKGROUND: Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. AIM: To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. METHODS: We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013-2018. Blood lead (B-Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B-Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. RESULTS: Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2-222). The median B-Pb concentration was 14 µg/L (range: 0.75-203). After adjusting for potential confounders, individuals in the fourth quartile of B-Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 µg/L increase in B-Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). CONCLUSIONS: This study shows an association between B-Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease.

Hexavalent chromium still a concern in Sweden - Evidence from a cross-sectional study within the SafeChrom project.

OBJECTIVES: Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Occupational Cr(VI) exposure can occur during different work processes, but the current exposure to Cr(VI) at Swedish workplaces is unknown. METHODS: This cross-sectional study (SafeChrom) recruited non-smoking men and women from 14 companies with potential Cr(VI) exposure (n = 113) and controls from 6 companies without Cr(VI) exposure (n = 72). Inhalable Cr(VI) was measured by personal air sampling (outside of respiratory protection) in exposed workers. Total Cr was measured in urine (pre- and post-shift, density-adjusted) and red blood cells (RBC) (reflecting Cr(VI)) in exposed workers and controls. The Bayesian tool Expostats was used to assess risk and evaluate occupational exposure limit (OEL) compliance. RESULTS: The exposed workers performed processing of metal products, steel production, welding, plating, and various chemical processes. The geometric mean concentration of inhalable Cr(VI) in exposed workers was 0.15 µg/m3 (95% confidence interval: 0.11-0.21). Eight of the 113 exposed workers (7%) exceeded the Swedish OEL of 5 µg/m3, and the Bayesian analysis estimated the share of OEL exceedances up to 19.6% for stainless steel welders. Median post-shift urinary (0.60 µg/L, 5th-95th percentile 0.10-3.20) and RBC concentrations (0.73 µg/L, 0.51-2.33) of Cr were significantly higher in the exposed group compared with the controls (urinary 0.10 µg/L, 0.06-0.56 and RBC 0.53 µg/L, 0.42-0.72). Inhalable Cr(VI) correlated with urinary Cr (rS = 0.64) and RBC-Cr (rS = 0.53). Workers within steel production showed the highest concentrations of inhalable, urinary and RBC Cr. Workers with inferred non-acceptable local exhaustion ventilation showed significantly higher inhalable Cr(VI), urinary and RBC Cr concentrations compared with those with inferred acceptable ventilation. Furthermore, workers with inferred correct use of respiratory protection were exposed to significantly higher concentrations of Cr(VI) in air and had higher levels of Cr in urine and RBC than those assessed with incorrect or no use. Based on the Swedish job-exposure-matrix, approximately 17 900 workers were estimated to be occupationally exposed to Cr(VI) today. CONCLUSIONS: Our study demonstrates that some workers in Sweden are exposed to high levels of the non-threshold carcinogen Cr(VI). Employers and workers seem aware of Cr(VI) exposure, but more efficient exposure control strategies are required. National strategies aligned with the European strategies are needed in order to eliminate this cause of occupational cancer.

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.

Exposure of Swedish adolescents to elements, persistent organic pollutants (POPs), and rapidly excreted substances - The Riksmaten adolescents 2016-17 national survey.

Adolescence is a period of significant physiological changes, and likely a sensitive window to chemical exposure. Few nation-wide population-based studies of chemical body burdens in adolescents have been published. In the national dietary survey Riksmaten Adolescents (RMA) 2016-17, over 13 chemical substance groups, including elements, chlorinated/brominated/fluorinated persistent organic pollutants (POPs) were analysed in blood, and in urine metabolites of phthalates/phthalate alternatives, phosphorous flame retardants, polycyclic aromatic hydrocarbons (PAHs), and pesticides, along with bisphenols and biocide/preservative/antioxidant/UV filter substances (N = 1082, ages 11-21). The aim was to characterize the body burdens in a representative population of adolescents in Sweden, and to compare results with human biomonitoring guidance values (HBM-GVs). Cluster analyses and Spearman's rank order correlations suggested that concentrations of substances with known common exposure sources and similar toxicokinetics formed obvious clusters and showed moderate to very strong correlations (r ≥ 0.4). No clusters were formed between substances from different matrices. Geometric mean (GM) concentrations of the substances were generally less than 3-fold different from those observed among adolescents in NHANES (USA 2015-16) and GerES V (Germany 2014-17). Notable exceptions were brominated diphenyl ethers (PBDEs) with >20-fold lower GM concentrations, and the biocide triclosan and ultraviolet (UV) filter benzophenone-3 with >15-fold lower mean concentrations in RMA compared to NHANES. Exceedance of the most conservative HBM-GVs were observed for aluminium (Al, 26% of subjects), perfluorooctanesulfonic acid (PFOS, 19%), perfluorooctanoic acid (PFOA, 12%), lead (Pb, 12%), MBP (dibutyl phthalate metabolite, 4.8%), hexachlorobenzene (HCB, 3.1%) and 3-phenoxybenzoic acid (PBA, pyrethroid metabolite, 2.2%). Males showed a higher proportion of exceedances than females for Pb, HCB and PFOS; otherwise no gender-related differences in exceedances were observed. A higher proportion of males than females had a Hazard Index (HI) of substances with liver and kidney toxicity and neurotoxicity >1. Industrialized countries with similarly high standards of living, with some exceptions, show comparable average body burdens of a variety of toxic chemicals among adolescents from the general population. The exceedances of HBM-GVs and HIs strongly suggests that further efforts to limit chemical exposure are warranted.

Lead-exposure associated miRNAs in humans and Alzheimer's disease as potential biomarkers of the disease and disease processes.

Alzheimer's disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively and hsa-miR-627 positively associated. In human brain derived from AD and AD control subjects all four miRNAs were detected. Moreover, two miRNAs (miR-3651, miR-664b-3p) showed significant differential expression in AD brains versus controls, in accordance with the change direction of lead exposure. The miRNAs' gene targets were validated for expression in the human brain and were found enriched in AD-relevant pathways such as axon guidance. Moreover, we identified several AD relevant transcription factors such as CREB1 associated with the identified miRNAs. These findings suggest that the identified miRNAs are involved in the development of AD and might be useful in the development of new, less invasive biomarkers for monitoring of novel therapies or of processes involved in AD development.

Low-level exposure to lead, cadmium and mercury, and histopathological findings in kidney biopsies.

BACKGROUND: Lead (Pb), cadmium (Cd) and mercury (Hg) are all nephrotoxic metals, and a large part of the body burden of Cd and Hg is found in the kidneys. There are, however, few studies on associations between exposure to these toxic metals and renal biopsy findings, and none at low-level exposure. AIM: To examine the hypothesis that low-level concentration of Pb, Cd or Hg in the kidneys is associated with histopathological changes in the kidneys. METHODS: We determined concentrations of Pb, Cd and Hg in kidney, blood and urine in 109 healthy kidney donors, aged 24-70 years. The renal biopsies were scored according to the Banff classification regarding tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, and arteriolohyalinosis. Kidney function was assessed based on glomerular filtration rate (GFR) as well as urinary excretion of albumin, low molecular weight proteins, kidney injury molecule 1 and N-acetylglucose aminidase. Associations between metal concentrations and histopathological changes, were assessed in models also including age, sex and smoking. RESULTS: The median kidney concentrations of Pb, Cd and Hg were 0.08, 13 and 0.21 µg/g, respectively. There were signs of tubular atrophy in 63%, interstitial fibrosis in 21%, glomerulosclerosis in 71%, arteriosclerosis in 47%, and arteriolohyalinosis in 36% of the donors, but, as could be expected, the histopathological findings were limited, mostly Banff grade 1. In models adjusted for age, sex and smoking, kidney Cd was positively associated with tubular atrophy (p = 0.03) and possibly with arteriolohyalinosis (p = 0.06). Kidney Hg was associated with arteriosclerosis (p = 0.004). DISCUSSION AND CONCLUSIONS: The results suggest that even low levels of Cd in the kidney can induce a mild degree of tubular atrophy. This is in line with previous findings at high-level Cd exposure. The association between kidney Hg and renal arteriosclerosis was unexpected, and may be a chance finding.

Cadmium Exposure and Coronary Artery Atherosclerosis: A Cross-Sectional Population-Based Study of Swedish Middle-Aged Adults.

BACKGROUND: The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined. OBJECTIVES: Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study. METHODS: Our analysis included 5,627 individuals (51% women), age 50-64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history. RESULTS: The median B-Cd concentration was 0.24µg/L. The prevalence of positive coronary artery calcium (CACS>0) was 41% and the prevalence of CACS≥100 was 13%. Relative to the lowest quartile (Q) of B-Cd (<0.16µg/L), the highest quartile (median 0.63µg/L) was associated with a small but significant increase in CACS>0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS≥100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS>0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS≥100 (17 cases in Q4). DISCUSSION: Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523.

Cadmium, total mercury, and lead in blood and associations with diet, sociodemographic factors, and smoking in Swedish adolescents.

BACKGROUND: Despite their vulnerability to the toxic effects of certain metals, biomonitoring data on adolescents are limited. In the present study, we assessed blood concentrations of toxic metals (cadmium [Cd], total mercury [Hg], and lead [Pb] in a national representative sample of Swedish adolescents. We also examined the associations of Cd, total Hg and Pb with habitual intakes of major energy-providing food groups and other possible determinants such as age, sex, household education, Nordic or non-Nordic origin, and smoking. METHODS: We analysed blood concentrations of Cd, total Hg, and Pb in a sample of 1099 adolescents from the Riksmaten Adolescents 2016-17 study in three age groups (mean age of 12, 15, and 18 years) using inductively coupled plasma mass spectrometry. The participants completed web-based questionnaires on food consumption frequency, sociodemographic factors and health status. Dietary data from two web-based 24-h dietary recalls were used to estimate the habitual intake of 10 major food groups. RESULTS: Almost all participants had detectable concentrations of Cd, total Hg, and Pb in whole blood. The median blood concentrations were 0.12 µg/L for Cd, 0.72 µg/L for total Hg, and 7.1 µg/L for Pb. Higher blood concentrations of Cd were observed in girls than in boys, whereas concentrations of total Hg and Pb were higher in boys. We observed an inverse association between Cd and meat intake. Total Hg concentrations were positively associated with intakes of fish, eggs, meat, and vegetables, and Pb concentrations were inversely associated with intakes of dairy products. Furthermore, smokers had higher concentrations of Cd and Pb. CONCLUSIONS: We found that fish was a potentially important source of exposure to total Hg in Swedish adolescents. No other food group was identified to have a strong impact on the blood levels of Cd, total Hg and Pb. Thirteen per cent of the adolescents had blood Pb concentrations above 12 µg/L, the reference point used in the risk assessment of Pb by the European Food Safety Authority (EFSA).

Effect of welding fumes on the cardiovascular system: a six-year longitudinal study.

Objective This study investigated whether low-to-moderate exposure to welding fumes is associated with adverse effects on the cardiovascular system. Methods To test this, we performed a longitudinal analysis of 78 mild steel welders and 96 controls; these subjects were examined twice, six years apart (ie, timepoints 1 and 2). All subjects (male and non-smoking at recruitment) completed questionnaires describing their health, work history, and lifestyle. We measured their blood pressure, endothelial function (by EndoPAT), and risk markers for cardiovascular disease [low-density lioprotein (LDL), homocysteine, C-reactive protein]. Exposure to welding fumes was assessed from the responses to questionnaires and measurements of respirable dust in their breathing zones adjusted for use of respiratory protection equipment. Linear mixed-effect regression models were used for the longitudinal analysis. Results Median respirable dust concentrations, adjusted for respirable protection, of the welders were 0.7 (5-95 percentile range 0.2-4.2) and 0.5 (0.1-1.9) mg/m 3at timepoints 1 and 2, respectively. Over the six-year period, welders showed a statistically significant increase in systolic [5.11 mm Hg, 95% confidence interval (CI) 1.92-8.31] and diastolic (3.12 mm Hg, 95% CI 0.74-5.5) blood pressure compared with controls (multi-variable adjusted mixed effect models). Diastolic blood pressure increased non-significantly by 0.22 mm Hg (95% CI -0.02-0.45) with every additional year of welding work. No consistent significant associations were found between exposure and endothelial function, LDL, homocysteine, or C-reactive protein. Conclusion Exposure to welding fumes at low-to-moderate levels is associated with increased blood pressure, suggesting that reducing the occupational exposure limit (2.5 mg/m 3for inorganic respirable dust in Sweden) is needed to protect cardiovascular health of workers.

Low-level cadmium exposure is associated with decreased cortical thickness, cortical area and trabecular bone volume fraction in elderly men: The MrOS Sweden study.

It is well known that high-level exposure to cadmium can cause bone disease such as osteoporosis, osteomalacia and fractures. However, the effect of low-level exposure, as found in the general population (mainly derived from diet and smoking), has only been assessed recently. The aim of this study was to examine if cadmium exposure in the general Swedish population causes other bone changes than decreased areal bone mineral density as measured by traditional DXA technology, e.g. changes in microstructure and geometry, such as cortical thickness or area, cortical porosity and trabecular bone volume. The study population consisted of 444 men, aged 70-81 years at inclusion year 2002-2004, from the Swedish cohort of the Osteoporotic Fractures in Men Study (MrOS). Cadmium was analyzed in baseline urine samples (U-Cd). Different parameters of bone geometry and microstructure were measured at the distal tibia at follow-up in 2009, including examination with high-resolution peripheral quantitative computed tomography (HR-pQCT). Associations between bone parameters and U-Cd in tertiles were estimated in multivariable analyses, including potential confounding factors (age, smoking, BMI, and physical activity). We found significant associations between U-Cd and several bone geometry or microstructure parameters, with 9% lower cortical thickness (p = 0.03), 7% lower cortical area (p = 0.04), and 5% lower trabecular bone volume fraction (p = 0.02) in the third tertile of U-Cd, using the first tertile as the reference. Furthermore, significant negative associations were found between log-transformed U-Cd and cortical thickness, cortical area, trabecular number and trabecular bone volume fraction, and a significant positive association with trabecular separation. The results indicate that low-level Cd exposure in the general population has negative effects on both cortical and trabecular bone.

Maternal Dietary Selenium Intake during Pregnancy Is Associated with Higher Birth Weight and Lower Risk of Small for Gestational Age Births in the Norwegian Mother, Father and Child Cohort Study.

Selenium is an essential trace element involved in the body's redox reactions. Low selenium intake during pregnancy has been associated with low birth weight and an increased risk of children being born small for gestational age (SGA). Based on data from the Norwegian Mother, Father and Child Cohort Study (MoBa) and the Medical Birth Registry of Norway (MBRN), we studied the association of maternal selenium intake from diet and supplements during the first half of pregnancy (n = 71,728 women) and selenium status in mid-pregnancy (n = 2628 women) with birth weight and SGA status, according to population-based, ultrasound-based and customized growth standards. An increase of one standard deviation of maternal dietary selenium intake was associated with increased birth weight z-scores (ß = 0.027, 95% CI: 0.007, 0.041) and lower SGA risk (OR = 0.91, 95% CI 0.86, 0.97) after adjusting for confounders. Maternal organic and inorganic selenium intake from supplements as well as whole blood selenium concentration were not associated with birth weight or SGA. Our results suggest that a maternal diet rich in selenium during pregnancy may be beneficial for foetal growth. However, the effect estimates were small and further studies are needed to elucidate the potential impact of selenium on foetal growth.

Blood Transcriptome Response to Environmental Metal Exposure Reveals Potential Biological Processes Related to Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disease which is manifested by a progressive and irreversible decline of cognition, memory loss, a shortened attention span, and changes in personality. Aging and genetic pre-dispositions, particularly the presence of a specific form of apolipoprotein E (APOE), are main risk factors of sporadic AD; however, a large body of evidence has shown that multiple environmental factors, including exposure to toxic metals, increase the risk for late onset AD. Lead (Pb) and cadmium (Cd) are ubiquitous toxic metals with a wide range of applications resulting in global distribution in the environment and exposure of all living organisms on earth. In addition to being classified as carcinogenic (Cd) and possibly carcinogenic (Pb) to humans by the International Agency for Research on Cancer, both compounds disrupt metal homeostasis and can cause toxic responses at the cellular and organismal levels. Pb toxicity targets the central nervous system and evidence for that has emerged also for Cd. Recent epidemiological studies show that both metals possibly are etiological factors of multiple neurodegenerative diseases, including Alzheimer's disease (AD). To further explore the association between metal exposure and AD risk we applied whole transcriptome gene expression analysis in peripheral blood leukocytes (PBLs) from 632 subjects of the general population, taken from the EnviroGenomarkers project. We used linear mixed effect models to associate metal exposure to gene expression after adjustment for gender, age, BMI, smoking, and alcohol consumption. For Pb exposure only few associations were identified, including a downregulation of the human eukaryotic translation initiation factor 5 (eIF5). In contrast, Cd exposure, particularly in males, revealed a much stronger transcriptomic response, featuring multiple pathways related to pathomolecular mechanisms of AD, such as endocytosis, neutrophil degranulation, and Interleukin-7 signaling. A gender stratified analysis revealed that the Cd responses were male-specific and included a downregulation of the APOE gene in men. This exploratory study revealed novel hypothetical findings which might contribute to the understanding of the neurotoxic effects of chronic Pb and Cd exposure and possibly improve our knowledge on the molecular mechanisms linking metal exposure to AD risk.

Cadmium and Lead Levels in Blood and Arsenic Levels in Urine among Schoolchildren Living in Contaminated Glassworks Areas, Sweden.

The Kingdom of Crystal, an area in southern Sweden famous for its many glassworks, is historically heavily burdened by pollution from this industry. Glass crust containing cadmium (Cd), lead (Pb), and arsenic (As) has been deposited around the area and used as filling. The purpose of this study was to monitor whether the high levels of metals in the contaminated soil were reflected in blood and urine among school children in this area. Blood and urine samples were collected from 87 children in 2017. The levels of cadmium (Cd-B) and lead (Pb-B) found in blood were determined by inductively coupled plasma mass spectrometry (ICP-MS). The speciation of As in urine (As-U) was performed by ion chromatography. The geometric mean of Cd-B and Pb-B among the children were 0.09 µg/L and 9.9 µg/L respectively. The geometric mean of inorganic As (AsIII and AsV) with metabolites in urine was 6.1 µg/L and 6.94 µg/g creatinine. Children in the study area had blood levels of Pb and Cd that correspond to levels generally found in Swedish children. The levels of inorganic As and its metabolites in urine were low and in the same magnitude as other children in Europe and the U.S.

Exposure to Mild Steel Welding and Changes in Serum Proteins With Putative Neurological Function-A Longitudinal Study.

Welders are exposed to high levels of metal particles, consisting mainly of iron and manganese (Mn) oxide. Metal particles, especially those containing Mn can be neurotoxic. In this exploratory study, we evaluated associations between welding and expression of 87 putative neurology-related proteins in serum in a longitudinal approach. The study cohort from southern Sweden included welders working with mild steel (n = 56) and controls (n = 67), all male and non-smoking, which were sampled at two timepoints (T1, T2) 6-year apart. Observed associations in the longitudinal analysis (linear mixed models) were further evaluated (linear regression models) in another cross-sectional sample which included welders (n = 102) and controls (n = 89) who were sampled only once (T1 or T2). The median respirable dust levels for welders after adjusting for respiratory protection was at T1 0.6 (5-95 percentile: 0.2-4.2) and at T2 0.5 (0.1-1.8) mg/m3. The adjusted median respirable Mn concentration was at T2 0.049 mg/m3 (0.003-0.314) with a Spearman correlation between adjusted respirable dust and respirable Mn of rS = 0.88. We identified five neurology-related proteins that were differentially expressed in welders vs. controls in the longitudinal sample, of which one (nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1; NMNAT1) was also differentially expressed in the cross-sectional sample. NMNAT1, an axon-protective protein linked to Alzheimers disease, was upregulated in welders compared with controls but no associations were discerned with degree of exposure (welders only: years welding, respirable dust, cumulative exposure). However, we identified five additional proteins that were associated with years welding (GCSF, EFNA4, CTSS, CLM6, VWC2; welders only) both in the longitudinal and in the cross-sectional samples. We also observed several neurology-related proteins that were associated with age and BMI. Our study indicates that low-to-moderate exposure to welding fumes is associated with changes in circulating levels of neurology-related proteins.

Exposure to wood smoke particles leads to inflammation, disrupted proliferation and damage to cellular structures in a human first trimester trophoblast cell line.

The ongoing transition to renewable fuel sources has led to increased use of wood and other biomass fuels. The physiochemical characteristics of biomass combustion derived aerosols depends on appliances, fuel and operation procedures, and particles generated during incomplete combustion are linked to toxicity. Frequent indoor wood burning is related to severe health problems such as negative effects on airways and inflammation, as well as chronic hypoxia and pathological changes in placentas, adverse pregnancy outcome, preterm delivery and increased risk of preeclampsia. The presence of combustion-derived black carbon particles at both the maternal and fetal side of placentas suggests that particles can reach the fetus. Air pollution particles have also been shown to inhibit trophoblast migration and invasion, which are vital functions for the development of the placenta during the first trimester. In this study we exposed a placental first trimester trophoblast cell line to wood smoke particles emitted under Nominal Burn rate (NB) or High Burn rate (HB). The particles were visible inside exposed cells and localized to the mitochondria, causing ultrastructural changes in mitochondria and endoplasmic reticulum. Exposed cells showed decreased secretion of the pregnancy marker human chorionic gonadotropin, increased secretion of IL-6, disrupted membrane integrity, disrupted proliferation and contained specific polycyclic aromatic hydrocarbons (PAHs) from the particles. Taken together, these results suggest that wood smoke particles can enter trophoblasts and have detrimental effects early in pregnancy by disrupting critical trophoblast functions needed for normal placenta development and function. This could contribute to the underlying mechanisms leading to pregnancy complications such as miscarriage, premature birth, preeclampsia and/or fetal growth restriction. This study support the general recommendation that more efficient combustion technologies and burning practices should be adopted to reduce some of the toxicity generated during wood burning.

Urban PM2.5 Induces Cellular Toxicity, Hormone Dysregulation, Oxidative Damage, Inflammation, and Mitochondrial Interference in the HRT8 Trophoblast Cell Line.

Objective: Epidemiological studies have found air pollution to be a driver of adverse pregnancy outcomes, including gestational diabetes, low term birth weight and preeclampsia. It is unknown what biological mechanisms are involved in this process. A first trimester trophoblast cell line (HTR-8/SVneo) was exposed to various concentrations of PM2.5 (PM2.5) in order to elucidate the effect of urban particulate matter (PM) of size <2.5 µm on placental function. Methods: PM2.5 were collected at a site representative of urban traffic and dispersed in cell media by indirect and direct sonication. The HTR-8 cells were grown under standard conditions. Cellular uptake was studied after 24 and 48 h of exposure by transmission electron microscopy (TEM). The secretion of human chorionic gonadotropin (hCG), progesterone, and Interleukin-6 (IL-6) was measured by ELISA. Changes in membrane integrity and H2O2 production were analyzed using the CellToxTM Green Cytotoxicity and ROSGloTM assays. Protease activity was evaluated by MitoToxTM assay. Mitochondrial function was assessed through high resolution respirometry in an Oroboros O2k-FluoRespirometer, and mitochondrial content was quantified by citrate synthase activity. Results: TEM analysis depicted PM2.5 cellular uptake and localization of the PM2.5 to the mitochondria after 24 h. The cells showed aggregated cytoskeleton and generalized necrotic appearance, such as chromatin condensation, organelle swelling and signs of lost membrane integrity. The mitochondria displayed vacuolization and disruption of cristae morphology. At 48 h exposure, a significant drop in hCG secretion and a significant increase in progesterone secretion and IL-6 production occurred. At 48 h exposure, a five-fold increase in protease activity and a significant alteration of H2O2 production was observed. The HTR-8 cells exhibited evidence of increased cytotoxicity with increasing exposure time and dose of PM2.5. No significant difference in mitochondrial respiration or mitochondrial mass could be demonstrated. Conclusion: Following exposure to air pollution, intracellular accumulation of PM may contribute to the placental dysfunction associated with pregnancy outcomes, such as preeclampsia and intrauterine growth restriction, through their direct and indirect effects on trophoblast protein secretion, hormone regulation, inflammatory response, and mitochondrial interference.

Smoking-Induced Risk of Osteoporosis Is Partly Mediated by Cadmium From Tobacco Smoke: The MrOS Sweden Study.

Cigarette smoking is a risk factor for osteoporosis and bone fracture. Moreover, smoking causes exposure to cadmium, which is a known risk factor for osteoporosis. It is hypothesized that part of smoking-induced osteoporosis may be mediated via cadmium from tobacco smoke. We investigated this hypothesis using mediation analysis in a Swedish cohort of elderly men. This study was performed in 886 elderly men from the Swedish cohort of the Osteoporotic Fractures in Men (MrOS) study. Urinary samples, bone mineral density (BMD), smoking data, and other background information were obtained at baseline in 2002-2004. Urinary cadmium was analyzed in baseline samples and adjusted for creatinine. The cohort was followed until August 2018 for fracture incidence, based on the X-ray register. Mediation analysis was conducted to evaluate the indirect effect (via cadmium) of smoking on both BMD and fractures. Time to first fracture was analyzed using the accelerated failure time (AFT) model and Aalen's additive hazard model. The mean level of urinary cadmium was 0.25 µg/g creatinine. There were significant inverse associations between smoking and total body, total hip, and trochanter BMD. The indirect effects via cadmium were estimated to be 43% of the total effects of smoking for whole-body BMD, and even more for total hip and trochanter BMD. Smoking was also associated with higher risk of all fractures and major osteoporosis fractures. The indirect effects via cadmium were largest in nonvertebral osteoporosis fractures and hip fractures, constituting at least one-half of the total effects, in both the AFT and Aalen's model. The findings in this study provide evidence that cadmium exposure from tobacco smoke plays an important role in smoking-induced osteoporosis © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.