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Background: Wide international variation in the prevalence of disabling low back pain (LBP) among working populations is not explained by known risk factors. It would be useful to know whether the drivers of this variation are specific to the spine or factors that predispose to musculoskeletal pain more generally.Methods: Baseline information about musculoskeletal pain and risk factors was elicited from 11 710 participants aged 20-59 years, who were sampled from 45 occupational groups in 18 countries. Wider propensity to pain was characterized by the number of anatomical sites outside the low back that had been painful in the 12 months before baseline ('pain propensity index'). After a mean interval of 14 months, 9055 participants (77.3%) provided follow-up data on disabling LBP in the past month. Baseline risk factors for disabling LBP at follow-up were assessed by random intercept Poisson regression.Results: After allowance for other known and suspected risk factors, pain propensity showed the strongest association with disabling LBP (prevalence rate ratios up to 2.6, 95% CI: 2.2-3.1; population attributable fraction 39.8%). Across the 45 occupational groups, the prevalence of disabling LBP varied sevenfold (much more than within-country differences between nurses and office workers), and correlated with mean pain propensity index (r = 0.58).Conclusions: Within our study, major international variation in the prevalence of disabling LBP appeared to be driven largely by factors predisposing to musculoskeletal pain at multiple anatomical sites rather than by risk factors specific to the spine.Significance: Our findings indicate that differences in general propensity to musculoskeletal pain are a major driver of large international variation in the prevalence of disabling low back pain among people of working age. [ABSTRACT FROM AUTHOR]

Ecuador is a Latin American country with one of the biggest biodiversities. At the same time, social and environmental problems are also big. Poverty, political and social problems as well as questions like old transport systems, imported hazards from industrialized countries and lack of information and weak health care systems are the framework of this situation. The most common problems are the use of heavy metals in many activities without safety and health protection, a low technological oil production during two decades, intensive use of pesticides in agriculture, and some other chemical risks. A limited capacity to develop prevention strategies, reduced technical and scientific skills, and the absence of a reliable information and control system, lead to a weak response mechanism. The Precautionary Principle could help to stimulate prevention, protection and to have a new tool to improve the interest in environment and health problems. Reinforcing the presence of international organizations like WHO and ILO, establishing bridges among scientific organizations from developed and developing countries and introducing the Precautionary Principle in the legislation and daily practices of industry and agriculture could lead to an improvement in our environment and health. [ABSTRACT FROM AUTHOR]

Ecuador is a Latin American country with one of the biggest biodiversities. At the same time, social and environmental problems are also big. Poverty, political and social problems as well as questions like old transport systems, imported hazards from industrialized countries and lack of information and weak health care systems are the framework of this situation. The most common problems are the use of heavy metals in many activities without safety and health protection, a low technological oil production during two decades, intensive use of pesticides in agriculture, and some other chemical risks. A limited capacity to develop prevention strategies, reduced technical and scientific skills, and the absence of a reliable information and control system, lead to a weak response mechanism. The Precautionary Principle could help to stimulate prevention, protection and to have a new tool to improve the interest in environment and health problems. Reinforcing the presence of international organizations like the World Health Organization or the International Labour Organization, establishing bridges among scientific organizations from developed and developing countries and introducing the Precautionary Principle in the legislation and daily practices of industry and agriculture could lead to an improvement in our environment and health. [ABSTRACT FROM AUTHOR]

Background: Despite accumulating evidence of an association between air pollution and renal disease, studies on the association between long-term exposure to air pollution and renal function are still contradictory. This study aimed to investigate this association in a large population with relatively low exposure and with improved estimation of renal function as well as renal injury biomarkers., Methods: We performed a cross-sectional analysis in the middle-aged general population participating in the Swedish CardioPulmonary bioImaging Study (SCAPIS; n = 30 154). Individual 10-year exposure to total and locally emitted fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), and nitrogen oxides (NO x ) were modelled using high-resolution dispersion models. Linear regression models were used to estimate associations between exposures and estimated glomerular filtration rate (eGFR, combined creatinine and cystatin C) and serum levels of renal injury biomarkers (KIM-1, MCP-1, IL-6, IL-18, MMP-2, MMP-7, MMP-9, FGF-23, and uric acid), with consideration of potential confounders., Results: Median long-term PM 2.5 exposure was 6.2 µg/m 3 . Almost all participants had a normal renal function and median eGFR was 99.2 mL/min/1.73 m 2 . PM 2.5 exposure was associated with 1.3% (95% CI 0.6, 2.0) higher eGFR per 2.03 µg/m 3 (interquartile range, IQR). PM 2.5 exposure was also associated with elevated serum matrix metalloproteinase 2 (MMP-2) concentration, with 7.2% (95% CI 1.9, 12.8) higher MMP-2 per 2.03 µg/m 3 . There was a tendency towards an association between PM 10 and higher levels of uric acid, but no associations were found with the other biomarkers. Associations with other air pollutants were null or inconsistent., Conclusion: In this large general population sample at low exposure levels, we found a surprising association between PM 2.5 exposure and a higher renal filtration. It seems unlikely that particle function would improve renal function. However, increased filtration is an early sign of renal injury and may be related to the relatively healthy population at comparatively low exposure levels. Furthermore, PM 2.5 exposure was associated with higher serum concentrations of MMP-2, an early indicator of renal and cardiovascular pathology., (© 2024. The Author(s).)

Objectives: Increasing epidemiological and experimental evidence suggests that particle exposure is an environmental risk factor for chronic kidney disease (CKD). However, only a few case-control studies have investigated this association in an occupational setting. Hence, our objective was to investigate associations between particle exposure and CKD in a large cohort of Swedish construction workers., Methods: We performed a retrospective cohort study in the Swedish Construction Workers' Cohort, recruited 1971-1993 (n=286 089). A job-exposure matrix was used to identify workers exposed to nine different particulate exposures, which were combined into three main categories (inorganic dust and fumes, wood dust and fibres). Incident CKD and start of renal replacement therapy (RRT) were obtained from validated national registries until 2021 and analysed using adjusted Cox proportional hazards models., Results: Exposure to inorganic dust and fumes was associated with an increased risk of CKD and RRT during working age (adjusted HR for CKD at age <65 years 1.15, 95% CI 1.05 to 1.26). The elevated risk did not persist after retirement age. Exposure to cement dust, concrete dust and diesel exhaust was associated with CKD. Elevated HRs were also found for quartz dust and welding fumes., Conclusions: Workers exposed to inorganic particles seem to be at elevated risk of CKD and RRT. Our results are in line with previous evidence of renal effects of ambient air pollution and warrant further efforts to reduce occupational and ambient particle exposure., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 (mm 2 ) and the presence of large plaques (>25 mm 2 ) 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 mm 2 (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 mm 2 (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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Inorganic arsenic (iAs) is a widespread toxic metalloid. It is well-known that iAs metabolism and its toxicity are mediated by polymorphisms in AS3MT and other genes. However, studies during pregnancy are scarce. We aimed to examine the role of genetic polymorphisms in AS3MT, GSTO2, N6AMT1, MTHFR, MTR, FTCD, CBS, and FOLH1 in iAs methylation efficiency during pregnancy., Methods: The study included 541 pregnant participants from the INMA (Environment and Childhood) Spanish cohort. Using high-performance liquid chromatography coupled to inductively coupled plasma-tandem mass, we measured arsenic (iAs and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)) in urine samples collected during the first trimester. iAs methylation efficiency was determined based on relative concentrations of the As metabolites in urine (%MMA, %DMA, and %iAs). Thirty-two single nucleotide polymorphisms (SNPs) in nine genes were determined in maternal DNA; AS3MT haplotypes were inferred. We assessed the association between genotypes/haplotypes and maternal As methylation efficiency using multivariate linear regression models., Results: The median %MMA and %DMA were 5.3 %, and 89 %, respectively. Ancestral alleles of AS3MT SNPs (rs3740393, rs3740390, rs11191453, and rs11191454) were significantly associated with higher %MMA, %iAs, and lower %DMA. Pregnant participants with zero copies of the GGCTTCAC AS3MT haplotype presented a higher %MMA. Statistically significant associations were also found for the FOLH1 SNP rs202676 (β 0.89 95%CI: 0.24, 1.55 for carriers of the G allele vs. the A allele)., Conclusions: Our study shows that ancestral alleles in AS3MT polymorphisms were associated with lower As methylation efficiency in early pregnancy and suggests that FOLH1 also plays a role in As methylation efficiency. These results support the hypothesis that As metabolism is multigenic, being a key element for identifying susceptible populations., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1 , ABCB1 , PON1 , CYP3A , BDNF , GSTP1 , MT2A , and APOE as well as AS3MT ) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 μg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

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., (This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.)

Background: Epidemiological studies linking type 2 diabetes (T2D) and exposure to per- and polyfluoroalkyl substances (PFAS), are limited and have yielded conflicting results. This register-based study aimed to investigate the risk of T2D among Swedish adults who had been exposed to PFAS from highly contaminated drinking water for decades., Methods: The study included 55,032 adults (aged ≥18 years) from the Ronneby Register Cohort, who ever lived in Ronneby during 1985-2013. Exposure was assessed using the yearly residential address and the absence ("never-high") or presence ("ever-high") of high PFAS contamination in the municipal drinking water supply; the latter was subdivided into "early-high" and "late-high" exposure with cut-off at 2005. Incident T2D cases were retrieved from the National Patient Register and the Prescription Register. Cox proportional hazard models with time-varying exposure were used to estimate hazard ratios (HRs). Stratified analyses were performed based on age (18-45 vs > 45)., Results: Elevated HRs for T2D were observed when comparing "ever-high" to "never-high" exposure (HR 1.18, 95% CI 1.03-1.35), as well as when comparing "early-high" (HR 1.12, 95% CI 0.98-1.50) or "late-high" (HR 1.17, 95% CI 1.00-1.37) to "never-high", after adjusting for age and sex. Individuals aged 18-45 years had even higher HRs. Adjusting for the highest-achieved education level attenuated the estimates, but the directions of associations remained. Elevated HRs were also found among those who had lived in areas with a heavily contaminated water supply for 1-5 years (HR 1.26, 95% CI 0.97-1.63) and 6-10 years (HR 1.25, 95% CI 0.80-1.94)., Conclusion: This study suggests an increased risk of T2D after long-term high PFAS exposure through drinking water. In particular, a higher risk of early onset diabetes was found, indicating increased susceptibility to PFAS-related health effects at younger ages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Multisite musculoskeletal pain is common and disabling. This study aimed to prospectively investigate the distribution of musculoskeletal pain anatomically, and explore risk factors for increases/reductions in the number of painful sites., Methods: Using data from participants working in 45 occupational groups in 18 countries, we explored changes in reporting pain at 10 anatomical sites on two occasions 14 months apart. We used descriptive statistics to explore consistency over time in the number of painful sites, and their anatomical distribution. Baseline risk factors for increases/reductions by ≥3 painful sites were explored by random intercept logistic regression that adjusted for baseline number of painful sites., Results: Among 8927 workers, only 20% reported no pain at either time point, and 16% reported ≥3 painful sites both times. After 14 months, the anatomical distribution of pain often changed but there was only an average increase of 0.17 painful sites. Some 14% workers reported a change in painful sites by ≥3. Risk factors for an increase of ≥3 painful sites included female sex, lower educational attainment, having a physically demanding job and adverse beliefs about the work-relatedness of musculoskeletal pain. Also predictives were as follows: older age, somatizing tendency and poorer mental health (each of which was also associated with lower odds of reductions of ≥3 painful sites)., Conclusions: Longitudinally, the number of reported painful sites was relatively stable but the anatomical distribution varied considerably. These findings suggest an important role for central pain sensitization mechanisms, rather than localized risk factors, among working adults., Significance: Our findings indicate that within individuals, the number of painful sites is fairly constant over time, but the anatomical distribution varies, supporting the theory that among people at work, musculoskeletal pain is driven more by factors that predispose to experiencing or reporting pain rather than by localized stressors specific to only one or two anatomical sites., (© 2022 European Pain Federation - EFIC®.)

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 0.24 μ g / 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 ( < 0.16 μ g / L ), the highest quartile (median 0.63 μ g / 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.

Background: Urine is often used for biomonitoring the exposure to elements. However, most studies report concentrations in spot urine samples, which may not accurately mirror the "gold standard" of complete 24-h (24 h) urine samples. There are relatively few data published for 24 h samples, and little information on the within- and between person variability., Objectives: The present study aimed at assessing variability within and between individuals in 24 h excretion for a number of elements in adults from the general population and the typical 24 h excretion of these elements. In addition, we assessed concentrations adjusted for creatinine and specific gravity (SG), and associations between elements., Methods: 60 healthy non-smokers (31 women and 29 men) from Sweden, aged 21-64 years, collected all urine during 24 h (split into six separate samples) on two occasions, about one week apart. Concentrations of As, Br, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Ni, P, Pb, S, Sb, Se, Sn, U, V, W, and Zn in urine were analyzed by inductively coupled plasma sector-field mass spectrometry (ICP-SF-MS) and 24 h excretion rates were calculated for each day. The ratio of between-individual variance and the total variance, the intra-class correlation (ICC) was calculated based on natural log-transformed 24 h excretion. Correlation coefficients were calculated between excretion rates (mass/24 h), and concentrations adjusted for creatinine and SG., Results: Geometric means (GM), and 90-percentiles are presented for each element. The 24 h excretion was higher in men than in women for most elements, and the difference was statistically significant for Cr, Cu, Fe, Li, P, Pb, S, Se, U, V, and Zn. However, for Cd and Co, the excretion was higher in women. Variability between days was low for Cd, Co, Hg, Pb, Sn, Se, V, and Zn (ICC 0.75-0.90), highest for Cr (ICC = 0.3) and Sb (ICC = 0.18), and moderate for the other elements. Spearman's rank correlation coefficients were about 0.8-0.9 for 17 elements, and 0.3-0.7 for Br, Cu, P, S, Se. Excretion of P and S were highly correlated, and also associated with excretion of most of the other elements, especially Cu, Se, V, and Zn. A high correlation was also found between As and Hg, between Mo and W, as well as between Cr, Fe and Mn., Conclusions: These data present normal variability of 24 h excretion of a number of elements, and can also be used as updated reference levels for elements with no or limited previous literature available. Information on variability within- and between individuals is important to know when designing studies with urine levels of elements used as exposure biomarker in studies of associations with health outcomes., (Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: The uterine environment may be important for the chromosomal telomere length (TL) at birth, which, in turn, influences disease susceptibility throughout life. However, little is known about the importance of specific nutritional factors., Objectives: We assessed the impact of multiple maternal nutritional factors on TL in placenta and cord blood., Methods: In a population-based mother-child cohort in northwestern Argentina, we measured maternal weight, BMI, body fat percentage (BFP), and several nutrients [selenium, magnesium, calcium, zinc, manganese, iodine, vitamin B-12, folate, 25-hydroxycholecalciferol (25(OH)D3)], hemoglobin, and homocysteine in maternal whole blood, serum, plasma, or urine during pregnancy (mean gestational week 27). We measured the relative TL (rTL) in placenta (n = 99) and cord blood (n = 98) at delivery by real-time PCR. Associations were evaluated by multivariable-adjusted linear regression., Results: The women's prepregnancy BMI (kg/m2; mean ± SD: 23.7 ± 4.1), body weight (55.4 ± 9.9 kg), and BFP (29.9 ± 5.5%), but not height (153 ± 5.3 cm), were inversely associated with placental rTL (P < 0.01 for all), with ∼0.5 SD shorter rTL for an IQR increase in prepregnancy body weight, BMI, or BFP. Also, impedance-based BFP, but not lean body mass, in the third trimester was associated with shorter placental rTL. In addition, serum vitamin B-12 (232 ± 96 pmol/L) in pregnancy (P = 0.038), but not folate or homocysteine, was associated with shorter placental rTL (0.2 SD for an IQR increase). In contrast, plasma 25(OH)D3 (46 ± 15 nmol/L) was positively associated with placental rTL (P < 0.01), which increased by 0.4 SD for an IQR increase in 25(OH)D3. No clear associations of the studied maternal nutritional factors were found with cord blood rTL., Conclusions: Maternal BMI, BFP, and vitamin B-12 were inversely associated, whereas 25(OH)D3 was positively associated, with placental TL. No association was observed with cord blood TL. Future studies should elucidate the role of placental TL for child health., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Lead exposure has been associated with increased incidence of adverse clinical cardiovascular outcomes. Atherosclerosis has been suggested as one of the underlying mechanisms, and findings from experimental studies support this, but human data are scarce., Objectives: Our objective was to determine the association between environmental lead exposure based on blood lead (B-Pb) concentrations and the prevalence of atherosclerotic plaque in the carotid artery., Methods: We used cross-sectional data from the Malmö Diet and Cancer Study cardiovascular cohort (MDCS-CC; recruitment in 1991-1994) covering 4,172 middle-aged men and women. B-Pb at baseline, measured by inductively coupled plasma mass spectrometry, was used as the exposure biomarker. The presence of atherosclerotic plaque in the carotid artery was determined by B-mode ultrasonography. We used logistic regression to estimate odds ratios (ORs) for prevalence of plaque in the carotid artery according to B-Pb quartiles., Results: The median B-Pb was 25 μ g / L (range: 1.5-258), and 36% of the cohort had any atherosclerotic plaque. After controlling for confounders and known cardiovascular risk factors, the OR for prevalence of plaque in the highest quartile (Q4) of B-Pb compared with the lowest quartile (Q1) was 1.35 (95% CI: 1.09, 1.66) in the total group, 1.58 (95% CI: 1.20, 2.08) among women, and 1.18 (95% CI: 0.83, 1.69) among men. Among women, associations were limited to those who were postmenopausal [OR for Q4 vs. Q 1 = 1.72 (95% CI: 1.26, 2.34) vs. OR = 0.96 (95% CI: 0.49, 1.89 in premenopausal women)]. Associations were weak and nonsignificant in never-smokers [OR for Q4 vs. Q 1 = 1.14 (95% CI: 0.81, 1.61)]., Discussion: Our study shows an association between B-Pb concentrations and occurrence of atherosclerotic plaque in the carotid artery, adding evidence for an underlying pro-atherogenic role of lead in cardiovascular disease. Associations appeared to be limited to postmenopausal (vs. premenopausal) women. https://doi.org/10.1289/EHP5057.

Background: Previous research has indicated that wide international variation in the prevalence of disabling low back pain among working populations is largely driven by factors predisposing to musculoskeletal pain more generally. This paper explores whether the same applies to disabling wrist/hand pain (WHP)., Methods: Using data from the Cultural and Psychosocial Influences on Disability (CUPID) study, we focused on workers from 45 occupational groups (office workers, nurses and other workers) in 18 countries. Among 11,740 participants who completed a baseline questionnaire about musculoskeletal pain and potential risk factors, 9082 (77%) answered a further questionnaire after a mean interval of 14 months, including 1373 (15%) who reported disabling WHP in the month before follow-up. Poisson regression was used to assess associations of this outcome with baseline risk factors, including the number of anatomical sites other than wrist/hand that had been painful in the 12 months before baseline (taken as an index of general propensity to pain)., Results: After allowance for other risk factors, the strongest associations were with general pain propensity (prevalence rate ratio for an index ≥6 vs. 0: 3.6, 95% confidence interval 2.9-4.4), and risk rose progressively as the index increased. The population attributable fraction for a pain propensity index > 0 was 49.4%. The prevalence of disabling WHP by occupational group ranged from 0.3 to 36.2%, and correlated strongly with mean pain propensity index (correlation coefficient 0.86)., Conclusion: Strategies to prevent disability from WHP among working populations should explore ways of reducing general propensity to pain, as well as improving the ergonomics of occupational tasks.

Background: The uterine environment may influence telomere length at birth, which is essential for cellular function, aging, and disease susceptibility over the lifespan. However, little is known about the impact of toxic chemicals on early-life telomeres. Therefore, we assessed the potential impact of multiple toxic metals on relative telomere length (rTL) in the maternal blood, cord blood, and placenta, as well as the potential modifying effects of pro-oxidants., Method: In a mother-child cohort in northern Argentina (n = 169), we measured multiple toxic metals in the maternal blood or urine collected during late pregnancy, as well as the placenta and cord blood collected at delivery, using inductively coupled plasma mass spectrometry (ICP-MS). We assessed associations of log 2 -transformed metal concentrations with rTL, measured in maternal and cord blood leukocytes and the placenta by real-time PCR, using multivariable-adjusted linear regression. Additionally, we tested for modifications by antioxidants (zinc, selenium, folate, and vitamin D 3 )., Results: Exposure to boron and antimony during pregnancy was associated with shorter maternal rTL, and lithium with longer maternal rTL; a doubling of exposure was associated with changes corresponding to 0.2-0.4 standard deviations (SD) of the rTL. Arsenic concentrations in the placenta (n = 98), blood, and urine were positively associated with placental rTL, about 0.2 SD by doubled arsenic. In the cord blood (n = 88), only lead was associated with rTL (inversely), particularly in boys (p for interaction 0.09). Stratifying by newborn sex showed ten times stronger association in boys (about 0.6 SD) than in girls. The studied antioxidants did not modify the associations, except that with antimony., Conclusions: Elevated exposure to boron, lithium, arsenic, and antimony was associated with maternal or newborn rTL in a tissue-specific, for lead also sex-specific, manner. Nutritional antioxidants did not generally influence the associations.

Background: Experimental studies show developmental toxicity of boron and we recently found impaired weight and length in newborns of mothers exposed to boron through drinking water during pregnancy., Objectives: To evaluate potential impact of pre- and postnatal boron exposure on infant anthropometry., Methods: In our mother-child cohort (n = 177) in Argentinean Andes, where drinking water concentrations of boron, lithium and arsenic have been found to vary considerably, we collected maternal blood and urine during and after pregnancy, placenta, breast milk, as well as infant urine and blood during the first 6 months of life. In all samples, boron and other potentially toxic elements were measured by ICP-MS. Infant weight (g), length (cm) and head circumference (cm) were measured at birth, 0-3 (n = 120) and/or 3-6 months (n = 120; 79 overlap) of age., Results: Boron concentrations in breast milk (range: 46-786 µg/L) correlated strongly with those in maternal serum (range: 47-624 µg/L; r s = 0.94) 0-3 months post-partum. In multivariable-adjusted linear regression, urinary boron (log 2 -transformed; range 60-9200 µg/L) in the youngest infants, but not maternal serum boron during pregnancy, was inversely associated with body weight at both 0-3 months (B: -141, 95% CI: -240; -42, p = 0.006) and 3-6 months (B: -200, 95% CI: -377; -23, p = 0.027). Infant urinary boron was also inversely associated with head circumference at 0-3 months (B: -0.39, 95% CI: -0.74; -0.04, p = 0.028), as well as length (B: -0.57, 95% CI: -1.1; -0.03, p = 0.040) and head circumference (B: -0.30, 95% CI: -0.64; 0.04, p = 0.083) at 3-6 months., Conclusions: The observed first evidence that elevated environmental boron exposure in early infancy may adversely affect growth supports previous findings of boron-related impaired fetal growth. More research is needed to verify the findings at older age and in other populations., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental lead exposure has been associated with decreased kidney function, but evidence from large prospective cohort studies examining low exposure levels is scarce. We assessed the association of low levels of lead exposure with kidney function and kidney disease., Study Design: Prospective population-based cohort., Setting & Participants: 4,341 individuals aged 46 to 67 years enrolled into the Malmö Diet and Cancer Study-Cardiovascular Cohort (1991-1994) and 2,567 individuals subsequently followed up (2007-2012)., Predictor: Blood lead concentrations in quartiles (Q1-Q4) at baseline., Outcomes: Change in estimated glomerular filtration rate (eGFR) between the baseline and follow-up visit based on serum creatinine level alone or in combination with cystatin C level. Chronic kidney disease (CKD) incidence (185 cases) through 2013 detected using a national registry., Measurements: Multivariable-adjusted linear regression models to assess associations between lead levels and eGFRs at baseline and follow-up and change in eGFRs over time. Cox regression was used to examine associations between lead levels and CKD incidence. Validation of 100 randomly selected CKD cases showed very good agreement between registry data and medical records and laboratory data., Results: At baseline, 60% of study participants were women, mean age was 57 years, and median lead level was 25 (range, 1.5-258) μg/L. After a mean of 16 years of follow-up, eGFR decreased on average by 6mL/min/1.73m 2 (based on creatinine) and 24mL/min/1.73m 2 (based on a combined creatinine and cystatin C equation). eGFR change was higher in Q3 and Q4 of blood lead levels compared with Q1 (P for trend = 0.001). The HR for incident CKD in Q4 was 1.49 (95% CI, 1.07-2.08) compared with Q1 to Q3 combined., Limitations: Lead level measured only at baseline, moderate number of CKD cases, potential unmeasured confounding., Conclusions: Low-level lead exposure was associated with decreased kidney function and incident CKD. Our findings suggest lead nephrotoxicity even at low levels of exposure., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Study Design: A cross-sectional survey with a longitudinal follow-up., Objectives: The aim of this study was to test the hypothesis that pain, which is localized to the low back, differs epidemiologically from that which occurs simultaneously or close in time to pain at other anatomical sites SUMMARY OF BACKGROUND DATA.: Low back pain (LBP) often occurs in combination with other regional pain, with which it shares similar psychological and psychosocial risk factors. However, few previous epidemiological studies of LBP have distinguished pain that is confined to the low back from that which occurs as part of a wider distribution of pain., Methods: We analyzed data from CUPID, a cohort study that used baseline and follow-up questionnaires to collect information about musculoskeletal pain, associated disability, and potential risk factors, in 47 occupational groups (office workers, nurses, and others) from 18 countries., Results: Among 12,197 subjects at baseline, 609 (4.9%) reported localized LBP in the past month, and 3820 (31.3%) nonlocalized LBP. Nonlocalized LBP was more frequently associated with sciatica in the past month (48.1% vs. 30.0% of cases), occurred on more days in the past month and past year, was more often disabling for everyday activities (64.1% vs. 47.3% of cases), and had more frequently led to medical consultation and sickness absence from work. It was also more often persistent when participants were followed up after a mean of 14 months (65.6% vs. 54.1% of cases). In adjusted Poisson regression analyses, nonlocalized LBP was differentially associated with risk factors, particularly female sex, older age, and somatizing tendency. There were also marked differences in the relative prevalence of localized and nonlocalized LBP by occupational group., Conclusion: Future epidemiological studies should distinguish where possible between pain that is limited to the low back and LBP that occurs in association with pain at other anatomical locations., Level of Evidence: 2.

Background: Boron is a metalloid found at highly varying concentrations in soil and water. Experimental data indicate that boron is a developmental toxicant, but the few human toxicity data available concern mostly male reproduction., Objectives: To evaluate potential effects of boron exposure through drinking water on pregnancy outcomes., Methods: In a mother-child cohort in northern Argentina (n=194), 1-3 samples of serum, whole blood and urine were collected per woman during pregnancy and analyzed for boron and other elements to which exposure occurred, using inductively coupled plasma mass spectrometry. Infant weight, length and head circumference were measured at birth., Results: Drinking water boron ranged 377-10,929μg/L. The serum boron concentrations during pregnancy ranged 0.73-605μg/L (median 133μg/L) and correlated strongly with whole-blood and urinary boron, and, to a lesser extent, with water boron. In multivariable-adjusted linear spline regression analysis (non-linear association), we found that serum boron concentrations above 80μg/L were inversely associated with birth length (B-0.69cm, 95% CI -1.4; -0.024, p=0.043, per 100μg/L increase in serum boron). The impact of boron appeared stronger when we restricted the exposure to the third trimester, when the serum boron concentrations were the highest (0.73-447μg/L). An increase in serum boron of 100μg/L in the third trimester corresponded to 0.9cm shorter and 120g lighter newborns (p=0.001 and 0.021, respectively)., Conclusions: Considering that elevated boron concentrations in drinking water are common in many areas of the world, although more screening is warranted, our novel findings warrant additional research on early-life exposure in other populations., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Nickel is a strong skin and respiratory sensitizer and a recognized carcinogen. Oil refineries are important sources of atmospheric emissions of toxic pollutants, including nickel. Populations residing close to oil refineries are at potential risk. The aim of this study was to evaluate the exposure to nickel in a population living close to the largest oil refinery in Ecuador, located in the city of Esmeraldas., Methodology: We recruited 47 workers from the oil refinery as well as 195 students from 4 different schools close to the plant and 94 students from another school 25 km far from the industry. Urinary nickel concentrations were used to assess the exposure to nickel., Results: Students from the school next to the oil refinery showed the highest urinary nickel concentrations while workers from the refinery showed the lowest concentrations. Median nickel concentrations were > 2µg/L in all study groups., Conclusions: The populations living close to the oil refineries are potentially exposed to nickel from atmospheric emissions. Further studies investigating nickel-related health effects in the population residing close to the refinery of Esmeralda are needed.

Background: Exposure to inorganic arsenic (iAs) through drinking water causes cancer. Alterations in mitochondrial DNA copy number (mtDNAcn) and telomere length in blood have been associated with cancer risk. We elucidated if arsenic exposure alters mtDNAcn and telomere length in individuals with different arsenic metabolizing capacity., Methods: We studied two groups in the Salta province, Argentina, one in the Puna area of the Andes (N = 264, 89% females) and one in Chaco (N = 169, 75% females). We assessed arsenic exposure as the sum of arsenic metabolites [iAs, methylarsonic acid (MMA), dimethylarsinic acid (DMA)] in urine (U-As) using high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. Efficiency of arsenic metabolism was expressed as percentage of urinary metabolites. MtDNAcn and telomere length were determined in blood by real-time PCR., Results: Median U-As was 196 (5-95 percentile: 21-537) μg/L in Andes and 80 (5-95 percentile: 15-1637) μg/L in Chaco. The latter study group had less-efficient metabolism, with higher %iAs and %MMA in urine compared with the Andean group. U-As was significantly associated with increased mtDNAcn (log2 transformed to improve linearity) in Chaco (β = 0.027 per 100 μg/L, p = 0.0085; adjusted for age and sex), but not in Andes (β = 0.025, p = 0.24). U-As was also associated with longer telomere length in Chaco (β = 0.016, p = 0.0066) and Andes (β = 0.0075, p = 0.029). In both populations, individuals with above median %iAs showed significantly higher mtDNAcn and telomere length compared with individuals with below median %iAs., Conclusions: Arsenic was associated with increased mtDNAcn and telomere length, particularly in individuals with less-efficient arsenic metabolism, a group who may have increased risk for arsenic-related cancer.

There is increasing evidence of adverse health effects due to elevated lithium exposure through drinking water but the impact on calcium homeostasis is unknown. This study aimed at elucidating if lithium exposure through drinking water during pregnancy may impair the maternal calcium homeostasis. In a population-based mother-child cohort in the Argentinean Andes (n=178), with elevated lithium concentrations in the drinking water (5-1660μg/L), blood lithium concentrations (correlating significantly with lithium in water, urine and plasma) were measured repeatedly during pregnancy by inductively coupled plasma mass spectrometry and used as exposure biomarker. Markers of calcium homeostasis included: plasma 25-hydroxyvitamin D3, serum parathyroid hormone (PTH), and calcium, phosphorus and magnesium concentrations in serum and urine. The median maternal blood lithium concentration was 25μg/L (range 1.9-145). In multivariable-adjusted mixed-effects linear regression models, blood lithium was inversely associated with 25-hydroxyvitamin D3 (-6.1nmol/L [95%CI -9.5; -2.6] for a 25μg/L increment in blood lithium). The estimate increased markedly with increasing percentiles of 25-hydroxyvitamin D3. In multivariable-adjusted mixed-effects logistic regression models, the odds ratio of having 25-hydroxyvitamin D3<30nmol/L (19% of the women) was 4.6 (95%CI 1.1; 19.3) for a 25μg/L increment in blood lithium. Blood lithium was also positively associated with serum magnesium, but not with serum calcium and PTH, and inversely associated with urinary calcium and magnesium. In conclusion, our study suggests that lithium exposure through drinking water during pregnancy may impair the calcium homeostasis, particularly vitamin D. The results reinforce the need for better control of lithium in drinking water, including bottled water., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

To inform case definition for neck/shoulder pain in epidemiological research, we compared levels of disability, patterns of association, and prognosis for pain that was limited to the neck or shoulders (LNSP) and more generalised musculoskeletal pain that involved the neck or shoulder(s) (GPNS). Baseline data on musculoskeletal pain, disability, and potential correlates were collected by questionnaire from 12,195 workers in 47 occupational groups (mostly office workers, nurses, and manual workers) in 18 countries (response rate = 70%). Continuing pain after a mean interval of 14 months was ascertained through a follow-up questionnaire in 9150 workers from 45 occupational groups. Associations with personal and occupational factors were assessed by Poisson regression and summarised by prevalence rate ratios (PRRs). The 1-month prevalence of GPNS at baseline was much greater than that of LNSP (35.1% vs 5.6%), and it tended to be more troublesome and disabling. Unlike LNSP, the prevalence of GPNS increased with age. Moreover, it showed significantly stronger associations with somatising tendency (PRR 1.6 vs 1.3) and poor mental health (PRR 1.3 vs 1.1); greater variation between the occupational groups studied (prevalence ranging from 0% to 67.6%) that correlated poorly with the variation in LNSP; and was more persistent at follow-up (72.1% vs 61.7%). Our findings highlight important epidemiological distinctions between subcategories of neck/shoulder pain. In future epidemiological research that bases case definitions on symptoms, it would be useful to distinguish pain that is localised to the neck or shoulder from more generalised pain that happens to involve the neck/shoulder region.

Somatising tendency, defined as a predisposition to worry about common somatic symptoms, is importantly associated with various aspects of health and health-related behaviour, including musculoskeletal pain and associated disability. To explore its epidemiological characteristics, and how it can be specified most efficiently, we analysed data from an international longitudinal study. A baseline questionnaire, which included questions from the Brief Symptom Inventory about seven common symptoms, was completed by 12,072 participants aged 20-59 from 46 occupational groups in 18 countries (response rate 70%). The seven symptoms were all mutually associated (odds ratios for pairwise associations 3.4 to 9.3), and each contributed to a measure of somatising tendency that exhibited an exposure-response relationship both with multi-site pain (prevalence rate ratios up to six), and also with sickness absence for non-musculoskeletal reasons. In most participants, the level of somatising tendency was little changed when reassessed after a mean interval of 14 months (75% having a change of 0 or 1 in their symptom count), although the specific symptoms reported at follow-up often differed from those at baseline. Somatising tendency was more common in women than men, especially at older ages, and varied markedly across the 46 occupational groups studied, with higher rates in South and Central America. It was weakly associated with smoking, but not with level of education. Our study supports the use of questions from the Brief Symptom Inventory as a method for measuring somatising tendency, and suggests that in adults of working age, it is a fairly stable trait.

Background: Impaired thyroid function is a common side effect of lithium medication. Recent data indicate that lithium exposure through drinking water, although providing much lower doses than the medication, may also affect thyroid hormone levels. However, the effects in susceptible groups like pregnant women are not known., Methods: In a population-based mother-child cohort in the Argentinean Andes (n = 194), an area with varying concentrations of lithium in the drinking water, we assessed lithium exposure repeatedly during pregnancy by measuring the concentrations in blood using inductively coupled plasma mass spectrometry. The markers of thyroid function included thyrotropin (TSH), free/total thyroxine (fT4/T4), free/total triiodothyronine (fT3/T3), thyroglobulin, and transthyretin in serum, sampled at the same time. Multiple potential confounders, including exposure to arsenic, cesium, and boron (elevated in water) as well as selenium and iodine (essential for thyroid function) were considered., Results: The lithium concentrations in blood [median 25 μg/L (0.0036 mmol/L); range 1.9-145 μg/L (0.000027-0.021 mmol/L)] correlated significantly with those in urine and drinking water (rs = 0.84, p < 0.001, and rs = 0.40, p < 0.001, respectively). Using linear quantile regression models, we found a positive association between blood lithium (log2 transformed) and TSH concentrations, particularly in the lowest percentiles of TSH (B = 0.20 mIU/L, [95% confidence interval 0.048-0.35] at the fifth percentile). We also found inverse associations of blood lithium with transthyretin, particularly at the highest percentiles, as well as with fT3 and T3, with less obvious variation across percentiles. Unexpectedly, blood cesium concentrations (median 111 μg/L, range 2.5-711 μg/L) were also inversely associated with fT3 and T3, particularly at the highest T3 percentiles, but not with TSH or transthyretin. Arsenic and boron exposure (also through drinking water) did not show any associations with the thyroid parameters., Conclusions: The study supports previous findings that lithium exposure through drinking water may impair thyroid function. The results regarding cesium exposure through drinking water are new. During pregnancy, impaired thyroid function may be detrimental for fetal development. The findings reinforce the need for better control of drinking water, including bottled water, as well as a health-based guideline value.

Methylation of the promoter of BRCA1 gene in peripheral blood (epimutation) has been associated with increased risk for breast cancer. Some studies have indicated that this epimutation is of constitutional origin and hence it could potentially be transmitted across generations. We used methylation sensitive high resolution melting technique to measure methylation of BRCA1 promoter in blood samples from 226 healthy women from the Andean region in Salta province, northern Argentina. In total 29 (13%) of the women showed detectable methylation of this gene. The analyses of mother-daughter pairs in this study, showed discordant methylation of BRCA1 between generations, with mothers tested positive for BRCA1 methylation in blood having daughters without signs of BRCA1 methylation, and vice versa. Our results show that the BRCA1 epimutation is unlikely transmitted from mother to daughters and hence may be a consequence of environmental exposure., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Exposure to inorganic arsenic has been identified as a risk factor for elevated blood pressure and cardiovascular disease. Our aim with this study was to elucidate effects of arsenic on blood pressure and early risk markers of cardiovascular disease in a population with efficient arsenic metabolism that can modify other arsenic-related health effects., Methods: The study included 225 women in the northern Argentinean Andes. Exposure to arsenic was assessed by the sum of arsenic metabolite concentrations in urine. Blood pressure was measured in the supine position. Blood samples were collected for measurement of hemoglobin, homocysteine, triglycerides, apolipoproteins A and B, and cytokines in separated plasma., Results: The median arsenic concentration in urine was 200 µg/L (range 22-545 µg/L). Unexpectedly, urinary arsenic concentrations were inversely associated with both systolic (p=0.081), and diastolic (p=0.002) blood pressure, and with the ratio of apolipoproteins B/A (p<0.001). There was no clear sign of increased inflammation, measured as cytokine concentrations, in relation to arsenic. Furthermore, urinary arsenic was associated with low hemoglobin concentrations (p<0.001)., Conclusions: Our results show that arsenic exposure was not associated with elevated levels of early risk markers for cardiovascular disease in this population. This provides evidence that the effects of arsenic on risk of cardiovascular disease differ between populations, which needs to be taken into account in risk assessment., (Copyright © 2015. Published by Elsevier Inc.)

Background: Lithium, used for treating bipolar disease, crosses freely the placenta and is classified as teratogenic. It is unclear to what extent environmental lithium exposure may affect fetal growth and development., Objectives: To elucidate potential effects of lithium exposure through drinking water during pregnancy on fetal size., Methods: We developed a prospective population-based mother-child cohort (N=194) in an area with highly varying drinking water lithium concentrations (5-1600 μg/L) in northern Argentinean Andes. Blood and urinary lithium concentrations (sampled repeatedly during pregnancy) were measured using inductively coupled plasma mass spectrometry. We measured fetal size by ultrasound in second and third trimesters, and weight, length and head circumference at birth. Multivariable models were used to examine associations between lithium exposure (continuous and in tertiles) and fetal size measures., Results: Lithium in maternal blood (median 25; range 1.9-145 μg/L) and urine (1645; 105-4600 μg/L) was inversely associated (apparently linearly) with all fetal measures (body, head and femur) in the second trimester, and with birth length (β -0.53 cm per 25 μg/L increase in blood lithium, 95%CI -1.0; -0.052). An increase of 100 μg/L in blood was associated with 2 cm shorter newborns (about one standard deviation)., Conclusions: Lithium exposure through drinking water was associated with impaired fetal size and this seemed to be initiated in early gestation. Further studies are warranted to confirm causality and to understand the mechanisms. If confirmed, these findings have public health relevance and emphasize the need for more data on lithium concentrations in drinking water, including bottled water., (Copyright © 2015. Published by Elsevier Ltd.)

Objectives: The direct dilution of blood with alkali has been introduced as an alternative to acid digestion for improvement of the analytical productivity when measuring trace elements using inductively coupled plasma mass spectrometry (ICP-MS). This study compared these two sample preparation methods for the ICP-MS determination of multiple elements in human blood and serum., Methods: Aliquots (0.2 or 0.5 mL) of human whole blood and serum samples, including reference samples (whole blood and serum), were subjected to alkali dilution (ammonia solution) or acid digestion (nitric acid). The samples were then analysed for their concentrations of Li, B, Mg, P, S, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Rb, Sr, Mo, Cd, Sb, Cs, Ba, Pb and U with a quadrupole ICP-MS instrument equipped with a collision/reaction cell., Results: Analysis of the reference materials showed that the alkali dilution and acid digestion methods provided equally good agreement with the reference values for Mg, Mn, Co, Ni, Cu, Zn, As, Se, Rb, Mo, Cd, Sb and Pb. The alkali dilution method generally gave better agreement with the reference values for Li, B, P, S, K, Cr and U, whereas acid digestion gave better agreement for Ca, Fe, Sr and Cs. Strong associations (R(2)>0.90) between the two methods were obtained for the concentrations of Li, B, Mn, Co, Cu, As, Se, Rb, Sr, Mo, Cd, Cs and Pb in the collected human whole blood and for Li, B, Mg, P, S, K, Fe, Co, Cu, Zn, As, Se, Rb, Sr, Sb and Cs in the collected serum., Conclusions: The results suggest that the alkali dilution method is suitable for the determination of Li, B, Mn, Co, Cu, Zn, As, Se, Rb and Sr in whole blood and serum; Mo, Cd and Pb in whole blood; and Sb in serum by ICP-MS. Acid digestion is preferred for Fe and for low concentrations of Cs., (Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Project: Ficoll density gradient centrifugation is widely used to separate cellular components of human blood. We evaluated the suitability to use erythrocytes and blood plasma obtained from Ficoll centrifugation for assessment of elemental concentrations., Procedure: We determined 22 elements (from Li to U) in erythrocytes and blood plasma separated by direct or Ficoll density gradient centrifugation, using inductively coupled plasma mass spectrometry., Results: Compared with erythrocytes and blood plasma separated by direct centrifugation, those separated by Ficoll had highly elevated iodine and Ba concentration, due to the contamination from the Ficoll-Paque medium, and about twice as high concentrations of Sr and Mo in erythrocytes. On the other hand, the concentrations of Ca in erythrocytes and plasma were markedly reduced by the Ficoll separation, to some extent also Li, Co, Cu, and U. The reduced concentrations were probably due to EDTA, a chelator present in the Ficoll medium. Arsenic concentrations seemed to be lowered by Ficoll, probably in a species-specific manner. The concentrations of Mg, P, S, K, Fe, Zn, Se, Rb, and Cs were not affected in the erythrocytes, but decreased in plasma. Concentrations of Mn, Cd, and Pb were not affected in erythrocytes, but in plasma affected by EDTA and/or pre-analytical contamination., Conclusions: Ficoll separation changed the concentrations of Li, Ca, Co, Cu, As, Mo, I, Ba, and U in erythrocytes and blood plasma, Sr in erythrocytes, and Mg, P, S, K, Fe, Zn, Se, Rb and Cs in blood plasma, to an extent that will invalidate evaluation of deficiencies or excess intakes., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Objective: To determine the daily intake of essential micronutrients and toxic elements through breast milk in exclusive and nonexclusive breastfed infants living in an area with major mine tailing deposition (n = 24), compared with a control area (n = 11)., Study Design: The milk volume ingested by 2 to 4 and 4 to 6 month infants was measured by a stable isotopic method. Elements in milk, maternal and infant urine, and drinking water were measured by inductively coupled plasma mass spectrometry (ICP-MS)., Results: Similar breast milk volume and essential micronutrients intake in groups of exclusively breastfed infants, but more cadmium, boron, and lithium through breastfeeding in experimental area was found. This exposure was even higher in the nonexclusively breastfed infants, who also ingested more arsenic, boron, and lithium than exclusive breastfed infants., Conclusion: The use of the deuterium and the ICP-MS methods made it possible to evaluate the exact amount of essential and toxic elements ingested by infants through breast milk demonstrating that lower amount of toxic elements are transferred to exclusive breastfed infants compared with those who additionally received nonmaternal milk., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

To explore definitions for multisite pain, and compare associations with risk factors for different patterns of musculoskeletal pain, we analysed cross-sectional data from the Cultural and Psychosocial Influences on Disability (CUPID) study. The study sample comprised 12,410 adults aged 20-59 years from 47 occupational groups in 18 countries. A standardised questionnaire was used to collect information about pain in the past month at each of 10 anatomical sites, and about potential risk factors. Associations with pain outcomes were assessed by Poisson regression, and characterised by prevalence rate ratios (PRRs). Extensive pain, affecting 6-10 anatomical sites, was reported much more frequently than would be expected if the occurrence of pain at each site were independent (674 participants vs 41.9 expected). In comparison with pain involving only 1-3 sites, it showed much stronger associations (relative to no pain) with risk factors such as female sex (PRR 1.6 vs 1.1), older age (PRR 2.6 vs 1.1), somatising tendency (PRR 4.6 vs 1.3), and exposure to multiple physically stressing occupational activities (PRR 5.0 vs 1.4). After adjustment for number of sites with pain, these risk factors showed no additional association with a distribution of pain that was widespread according to the frequently used American College of Rheumatology criteria. Our analysis supports the classification of pain at multiple anatomical sites simply by the number of sites affected, and suggests that extensive pain differs importantly in its associations with risk factors from pain that is limited to only a small number of anatomical sites., (Copyright © 2013 International Association for the Study of Pain. All rights reserved.)

Background: In humans, inorganic arsenic is metabolized to methylated metabolites mainly by arsenic (+3 oxidation state) methyltransferase (AS3MT). AS3MT polymorphisms are associated with arsenic metabolism efficiency. Recently, a putative N-6-adenine-specific DNA methyltransferase 1 (N6AMT1) was found to methylate arsenic in vitro., Objective: We evaluated the role of N6AMT1 polymorphisms in arsenic methylation efficiency in humans., Methods: We assessed arsenic methylation efficiency in 188 women exposed to arsenic via drinking water (~ 200 µg/L) in the Argentinean Andes by measuring the relative concentrations of arsenic metabolites in urine [inorganic arsenic, methylarsonic acid (MMA), and dimethylarsinic acid] by high-performance liquid chromatography coupled with hydride generation and inductively coupled plasma mass spectrometry. We performed genotyping for N6AMT1 and AS3MT polymorphisms by Taqman assays, and gene expression (in blood; n = 63) with Illumina HumanHT-12 v4.0., Results: Five N6AMT1 single nucleotide polymorphisms (SNPs; rs1997605, rs2205449, rs2705671, rs16983411, and rs1048546) and two N6AMT1 haplotypes were significantly associated with the percentage of MMA (%MMA) in urine, even after adjusting for AS3MT haplotype. %MMA increased monotonically according to the number of alleles for each SNP (e.g., for rs1048546, mean %MMA was 7.5% for GG, 8.8% for GT, and 9.7% for TT carriers). Three SNPs were in linkage disequilibrium (R2 > 0.8). Estimated associations for joint effects of N6AMT1 (haplotype 1) and AS3MT (haplotype 2) were generally consistent with expectations for additive effects of each haplotype on %MMA. Carriers of N6AMT1 genotypes associated with lower %MMA showed the lowest N6AMT1 expression, but associations were monotonic according to copy number for only one genotype and one haplotype., Conclusions: N6AMT1 polymorphisms were associated with arsenic methylation in Andean women, independent of AS3MT. N6AMT1 polymorphisms may be susceptibility markers for arsenic-related toxic effects.

To compare the prevalence of disabling low back pain (DLBP) and disabling wrist/hand pain (DWHP) among groups of workers carrying out similar physical activities in different cultural environments, and to explore explanations for observed differences, we conducted a cross-sectional survey in 18 countries. Standardised questionnaires were used to ascertain pain that interfered with everyday activities and exposure to possible risk factors in 12,426 participants from 47 occupational groups (mostly nurses and office workers). Associations with risk factors were assessed by Poisson regression. The 1-month prevalence of DLBP in nurses varied from 9.6% to 42.6%, and that of DWHP in office workers from 2.2% to 31.6%. Rates of disabling pain at the 2 anatomical sites covaried (r = 0.76), but DLBP tended to be relatively more common in nurses and DWHP in office workers. Established risk factors such as occupational physical activities, psychosocial aspects of work, and tendency to somatise were confirmed, and associations were found also with adverse health beliefs and group awareness of people outside work with musculoskeletal pain. However, after allowance for these risk factors, an up-to 8-fold difference in prevalence remained. Systems of compensation for work-related illness and financial support for health-related incapacity for work appeared to have little influence on the occurrence of symptoms. Our findings indicate large international variation in the prevalence of disabling forearm and back pain among occupational groups carrying out similar tasks, which is only partially explained by the personal and socioeconomic risk factors that were analysed., (Copyright © 2013 International Association for the Study of Pain. All rights reserved.)

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.

The transfer of lithium and boron from exposed mothers to fetuses and breast-fed infants was investigated in areas in northern Argentina and Chile with up to 700 μg lithium/L and 5-10 mg boron/L in drinking water. Maternal and cord blood concentrations were strongly correlated and similar in size for both lithium (47 and 70 μg/L, respectively) and boron (220 and 145 μg/L, respectively). The first infant urine produced after birth contained the highest concentrations (up to 1700 μg lithium/L and 14,000 μg boron/L). Breast-milk contained 40 and 60% of maternal blood concentrations of lithium and boron, respectively (i.e. about 30 and 250 μg/L, respectively, in high exposure areas), and infant urine concentrations decreased immediately after birth (120 μg lithium/L and 920 μg boron/L). We conclude that lithium and boron easily passed the placenta to the fetus, and that exclusively breast-fed infants seemed to have lower exposure than formula-fed infants., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Traditional gold mining, using metallic mercury (Hg(0)) to form gold amalgam, followed by burning to remove the Hg(0), is widely used in South America, Africa and Asia. The gold is sold to merchants who burn it again to eliminate remaining Hg(0). In Ecuador, 200 gold miners, 37 gold merchants and 72 referents were studied. The median Hg concentrations in urine (U-Hg) were 3.3 (range 0.23-170), 37 (3.2-420), and 1.6 (0.2-13)μg/g creatinine, respectively, and in whole blood (B-Hg) were 5.2, 30, and 5.0 μg/L, respectively. Biomarker concentrations among merchants were statistically significantly higher than among miners and referents; also the miners differed from the referents. Burning of gold amalgam among miners was intermittent; U-Hg decreased in the burning-free period. In computerized neuromotor examinations, B-Hg and U-Hg concentrations were associated with increases in the centre frequency of the tremor, as well as in reaction time and postural stability.Retention of Hg (B-Hg), and the elimination rate (U-Hg) appears to be modified by polymorphism in a gene of an enzyme in the glutathione synthesis (GCLM), but there were no significant genetic modifications for the associations between exposure and neurotoxicity.Thus, the gold merchants have a much higher exposure and risk than the miners, in whom the exposure varies over time. The metabolism of Hg is modified by genetic traits. The present exposure to Hg had limited neurotoxic effects., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)