Occupational particle exposure and chronic kidney disease: a cohort study in Swedish construction workers.

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.

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.

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.

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.

Exposure to high levels of PFAS through drinking water is associated with increased risk of type 2 diabetes-findings from a register-based study in Ronneby, Sweden.

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.

Placental and Cord Blood Telomere Length in Relation to Maternal Nutritional Status.

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.

Exploring telomere length in mother-newborn pairs in relation to exposure to multiple toxic metals and potential modifying effects by nutritional factors.

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 log2-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 D3). 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.

Pre- and postnatal environmental boron exposure and infant growth: Results from a mother-child cohort in northern Argentina.

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; rs = 0.94) 0-3 months post-partum. In multivariable-adjusted linear regression, urinary boron (log2-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.

Determinants of international variation in the prevalence of disabling wrist and hand pain.

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.

Blood Lead Levels and Decreased Kidney Function in a Population-Based Cohort.

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/1.73m2 (based on creatinine) and 24mL/min/1.73m2 (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.

Exposure to lithium through drinking water and calcium homeostasis during pregnancy: A longitudinal study.

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.

The effects of arsenic exposure on blood pressure and early risk markers of cardiovascular disease: Evidence for population differences.

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.

Maternal-child transfer of essential and toxic elements through breast milk in a mine-waste polluted area.

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.

Influence of genetic polymorphisms on arsenic methylation efficiency during pregnancy: Evidence from a Spanish birth cohort.

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 (ß 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.

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.

Patterns of change of multisite pain over 1 year of follow-up and related risk factors.

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.

Normal variability of 22 elements in 24-hour urine samples - Results from a biobank from healthy non-smoking adults.

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.

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.

Blood Lead Levels and Risk of Atherosclerosis in the Carotid Artery: Results from a Swedish Cohort.

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 25µg/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. Q1=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. Q1=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.

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

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

Epidemiological Differences Between Localized and Nonlocalized Low Back Pain.

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.