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.

Work-related neck and upper limb disorders - quantitative exposure-response relationships adjusted for personal characteristics and psychosocial conditions.

BACKGROUND: We have previously reported quantitative exposure-response relationships between physical exposures recorded by technical methods, and complaints and diagnoses in the neck/shoulders, and the elbows/hands, based on group data. In the present study the number of workers was doubled, and information on individual factors, and psychosocial working conditions was used. Relationships between various kinds of exposure and response have been analysed in this larger and more detailed sample. METHODS: The prevalence of complaints (Nordic Questionnaire) and diagnoses (clinical examination) were recorded in a number of occupational groups within which the participants had similar work tasks, 34 groups of female employees (N = 4733 women) and 17 groups of male employees (N = 1107 men). Age and other individual characteristics were recorded, as well as psychosocial work environment factors (job-content questionnaire) for most participants. Postures and velocities (inclinometry) of the head (N = 505) and right upper arm (N = 510), right wrist postures and velocities (electrogoniometry; N = 685), and muscular activity (electromyography; EMG) in the right trapezius muscle (N = 647) and forearm extensors (N = 396) were recorded in representative sub-groups. Exposure-response relationships between physical exposure and musculoskeletal disorders, adjusted for individual factors with Poisson regression were then calculated. The effect of introducing psychosocial conditions into the models was also assessed. RESULTS: Associations were found between head velocity, trapezius activity, upper arm velocity, forearm extensor activity and wrist posture and velocity, and most neck/shoulder and elbow/hand complaints and diagnoses. Adjustment for age, other individual characteristics and psychosocial work conditions had only a limited effect on these associations. For example, the attributable fraction for tension neck syndrome among female workers with the highest quintile of trapezius activity was 58%, for carpal tunnel syndrome versus wrist velocity it was 92% in men in the highest exposure quintile. CONCLUSIONS: Based on the findings, we propose threshold limit values for upper arm and wrist velocity.

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.

Fish consumption and risk of stroke: a second prospective case-control study from northern Sweden.

BACKGROUND: Fish consumption has been concluded to be associated with decreased risk of stroke in several reviews. However, among men, but not women, an increased risk of stroke was previously found at high fish consumption (>3 meals/week) in northern Sweden. This study investigates if previous results on elevated stroke risk with high fish consumption in men in northern Sweden can be confirmed in a larger study with new cases in the same population. METHODS: A prospective nested case-control study was performed within the population-based Northern Sweden Health and Disease Study cohort. Information on fish consumption, other lifestyle and medical data was collected at baseline. Incident stroke cases (1987-2007, n = 735) were identified and 2698 controls matched for gender, age, year of baseline and geographical region. RESULTS: There were no associations between total fish or fatty fish consumption and stroke risk; thus the previous finding of increased risk of stroke with high fish consumption in men could not be repeated. High intake of lean fish (>twice/week compared to < once/month) was associated with increased stroke risk in men [OR 1.80 (95% CI 1.00, 3.21), but not in women [OR 0.50 (95% CI 0.24, 1.10)]. The association was driven by men living alone. CONCLUSIONS: The previous association between high total fish consumption and risk of stroke in men could not be repeated. The increased risk found in men with high intake of lean fish may be due to chance or confounding specific for this group.

Exposure-response relationships for work-related neck and shoulder musculoskeletal disorders--Analyses of pooled uniform data sets.

There is a lack of quantitative data regarding exposure-response relationships between occupational risk factors and musculoskeletal disorders in the neck and shoulders. We explored such relationships in pooled data from a series of our cross-sectional studies. We recorded the prevalence of complaints/discomfort (Nordic Questionnaire) and diagnoses (physical examination) in 33 groups (24 female and 9 male) within which the workers had similar work tasks (3141 workers, of which 817 were males). In representative sub-groups, we recorded postures and velocities of the head (N = 299) and right upper arm (inclinometry; N = 306), right wrist postures and velocities (electrogoniometry; N = 499), and muscular activity (electromyography) in the right trapezius muscle (N = 431) and forearm extensors (N = 206). We also assessed the psychosocial work environment (Job Content Questionnaire). Uni- and multivariate linear meta-regression analysis revealed several statistically significant group-wise associations. Neck disorders were associated with head inclination, upper arm elevation, muscle activity of the trapezius and forearm extensors and wrist posture and angular velocity. Right-side shoulder disorders were associated with head and upper arm velocity, activity in the trapezius and forearm extensor muscles and wrist posture and angular velocity. The psychosocial work environment (low job control, job strain and isostrain) was also associated with disorders. Women exhibited a higher prevalence of neck and shoulder complaints and tension neck syndrome than men, when adjusting for postures, velocities, muscular activity or psychosocial exposure. In conclusion, the analyses established quantitative exposure-response relationships between neck and shoulder disorders and objective measures of the physical workload on the arm. Such information can be used for risk assessment in different occupations/work tasks, to establish quantitative exposure limits, and for the evaluation of preventive measures.

Late effects of low blood lead concentrations in children on school performance and cognitive functions.

BACKGROUND: Although it is known that lead is a neurotoxin that negatively impacts cognitive functions at low blood concentrations (B-Pb), little is known about the impact of early exposure on later cognitive functions. OBJECTIVES: This study assesses the effects of very low lead exposure in early childhood on teenage cognitive performance. METHODS: Using data collected between 1978 and 2007, we analyzed B-Pb (median 30 µg/L; six-fold decrease over time) in 3176 Swedish children (age 7-12). School performance in grade 9 (age 16; boys and girls) and over-all IQs measured during conscription examinations (age 18-19; mainly boys) were obtained from registers. In multivariate models, potential confounders (age at blood sampling, sex, parents' education, family economy, and country of birth of child and parents) and effect modifiers (socioeconomic; father's IQ at conscription examination) were included. RESULTS: There were statistically significant adjusted negative associations between school performance (Grades up to 1991: P<0.0001; Merits 1992-2007:P<0.0001) and IQ (P=0.03) and B-Pb. The dose-response relationships were non-linear. Effects were more pronounced for B-Pb≤50 µg/L than for higher levels. In the B-Pb range 5-50 µg/L, the average IQ loss corresponded to about 5 IU. There was no significant effect modification associated with socioeconomic factors. CONCLUSIONS: Lead causes neurotoxic effects at very low exposures (B-Pb<50 µg/L) in childhood and these effects remain for many years.

Genetic modification of ALAD and VDR on lead-induced impairment of hearing in children.

Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity. Two cohorts of children were examined for hearing [pure-tone audiometry (PTA), brain stem auditory evoked potentials (BAEP)], acoustic otoemission (transient emission evoked by a click) and blood-lead concentrations (B-Pb). The children were genotyped for polymorphisms in ALAD and VDR. The median B-Pbs were 55 and 36µg/L in the two cohorts (merged cohort 45µg/L). B-Pb was significantly associated with impaired hearing when tested with PTA (correlation coefficient rS=0.12; P<0.01), BAEP (rS=0.18; P<0.001) and otoemission (rS=-0.24; P<0.001). VDR significantly modified the lead-induced effects on PTA. Carriers of the VDR alleles BsmI B, VDR TaqI t and VDR FokI F showed greater toxic effects on PTA, compared to BsmI bb, VDR TaqI TT and VDR FokI ff carriers. No significant interaction was found for ALAD. Lead impairs hearing functions in the route from the cochlea to the brain stem at low-level exposure, and polymorphisms in VDR significantly modify these effects.

Disturbance of posture in children with very low lead exposure, and modification by VDR FokI genotype.

INTRODUCTION AND OBJECTIVE: Lead has a negative effect on the central nervous system (CNS), inter alia indicated by disturbance of posture. However, knowledge of the CNS effects at low exposure is insufficient. Individuals differ in vulnerability, possibly because of genetic predisposition. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity. The objective of the study was to determine whether very low lead exposure affects posture in children, and whether ALAD and VDR genotypes modify the effect. MATERIALS AND METHODS: In 1996-2001, 108 (age 5-13, mean 6.9), and in 2008-2010 231 (age 5-11, mean 7.9) children from Poland were tested by posturography and blood-lead concentration (B-Pb; medians 50 and 36 µg/L, respectively). The children were genotyped for ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI). RESULTS: There were correlations between posture and B-Pb (sway area with closed eyes: rS=0.24, P<0.001; velocity: rS=0.21, P<0.001). Significant effects (adjusted for the potential confounders height and mother´s education) were present already at (ln-transformed) B-Pb<50 µg/L [ß (regression coefficient) for sway area 0.025, p=0.001), and even stronger than at higher levels (ß=0.006, p=0.06, respectively)]. The ff carriers in VDR FokI polymorphism were more susceptible to the effect of lead on the balance system, while other VDR or ALAD genotypes did not significantly modify the effect. CONCLUSIONS: Effects on CNS, as reflected by disturbances of posture, were present at very low lead exposure (B-Pb<50 µg/L), and the effect was significantly greater at such low B-Pbs than at higher. VDR FokI significantly modified the effect.

Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women.

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), in 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk.

Cadmium concentrations in human blood and urine are associated with polymorphisms in zinc transporter genes.

BACKGROUND: Variation in susceptibility to cadmium (Cd) toxicity may partly be due to differences in Cd toxicokinetics. Experimental studies indicate that zinc (Zn) homeostasis proteins transport Cd. OBJECTIVE: To evaluate the potential effect of variation in Zn-transporter genes (SLC39A8 and SLC39A14) on Cd concentrations in blood and urine. METHODS: We studied women from the Argentinean Andes [median urinary Cd concentration (U-Cd) = 0.24 µg L(-1); erythrocyte Cd (Ery-Cd) = 0.75 µg L(-1) (n = 172)] and from rural Bangladesh [U-Cd = 0.54 µg L(-1) (n = 359), Ery-Cd = 1.1 µg L(-1) (n = 400)]. Polymorphisms (n = 36) were genotyped with Sequenom. Gene expression was measured in whole blood with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: Polymorphisms in SLC39A8 and SLC39A14 were associated with Ery-Cd concentrations in the Andean population. For SLC39A14, women carrying GT or TT genotypes of rs4872479 had 1.25 [95% confidence interval (CI) = 1.07-1.46] times higher Ery-Cd than women carrying GG. Also, women carrying AG or AA of rs870215 had 1.17 (CI 1.01-1.32) times higher Ery-Cd than those carrying GG. For SLC39A8, women carrying AG or GG of rs10014145 had 1.18 (CI 1.03-1.35) times higher Ery-Cd than those with AA, and carriers of CA or AA of rs233804 showed 1.22 (CI 1.04-1.42) times higher Ery-Cd than CC. The Bangladeshi population had similar, but statistically non-significant associations between some of these SNPs and Ery-Cd. In the Andean population, the genotypes of SLC39A14 rs4872479 and rs870215 associated with lower Ery-Cd showed positive correlations with plasma-Zn (P-Zn) and SLC39A14 expression. CONCLUSIONS: Polymorphisms in SLC39A14 and SLC39A8 seemed to affect blood Cd concentrations, for SLC39A14 this effect may occur via differential gene expression.

Non-renal effects and the risk assessment of environmental cadmium exposure.

BACKGROUND: Exposure to cadmium (Cd) has long been recognized as a health hazard, both in industry and in general populations with high exposure. Under the currently prevailing health risk assessment, the relationship between urinary Cd (U-Cd) concentrations and tubular proteinuria is used. However, doubts have recently been raised regarding the justification of basing the risk assessment on this relationship at very low exposure. OBJECTIVES: Our objective was to review available information on health effects of Cd exposure with respect to human health risk assessment. DISCUSSION: The associations between U-Cd and urinary proteins at very low exposure may not be due to Cd toxicity, and the clinical significance of slight proteinuria may also be limited. More importantly, other effects have been reported at very low Cd exposure. There is reason to challenge the basis of the existing health risk assessment for Cd. Our review of the literature found that exposure to low concentrations of Cd is associated with effects on bone, including increased risk of osteoporosis and fractures, and that this observation has implications for the health risk assessment of Cd. Other effects associated with Cd should also be considered, in particular cancer, although the information is still too limited for appropriate use in quantitative risk assessment. CONCLUSION: Non-renal effects should be considered critical effects in the health risk assessment of Cd.

Investigation of lead concentrations in whole blood, plasma and urine as biomarkers for biological monitoring of lead exposure.

Lead in blood is a major concept in biomonitoring of exposure but investigations of its alternatives are scarce. The aim of the study was to describe different lead biomarkers' variances, day-to-day and between individuals, estimating their fraction of the total variance. Repeated sampling of whole blood, plasma and urine were conducted for 48 lead-exposed men and 20 individuals under normal environmental lead exposure, in total 603 measurements. For lead workers, the fraction of the total variance attributed to differences between individuals was 91% for whole-blood lead (geometric mean 227 µg/l; geometric standard deviation (GSD): 1.55 µg/l); plasma 78% (0.57 µg/l; GSD: 1.84 µg/l); density-adjusted urine 82%; and unadjusted urine 75% (23.7 µg/l; GSD: 2.48 µg/l). For the individuals under normal lead exposure, the corresponding fractions were 95% of the total variance for whole blood (20.7 µg/l; GSD: 8.6 µg/l), 15% for plasma (0.09 µg/l; GSD: 0.04 µg/l), 87% for creatinine-adjusted urine and 34% for unadjusted (10.8 µg/l; GSD: 6.7 µg/l). Lead concentration in whole blood is the biomarker with the best ability to discriminate between individuals with different mean concentration. Urinary and plasma lead also performed acceptably in lead workers, but at low exposures plasma lead was too imprecise. Urinary adjustments appear not to increase the between-individual fraction of the total variance among lead workers but among those with normal lead exposure.

Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by δ-aminolevulinic acid dehydratase gene polymorphism.

UNLABELLED: Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that δ-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), ALAD polymorphism (rs1800435, ALAD1/2; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary δ-aminolevulic acid), on the kidneys (urinary albumin, ß2-microglobulin and N-acetyl-ß-d-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27)µg/L, B-Pb 401 (110-950)µg/L, and U-Pb 188 (22-590)µg/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: rS=-0.10 to 0.79; B-Pb: rS=-0.08 to 0.75; all p<0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p=0.04) in ALAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb. CONCLUSIONS: (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics.

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

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

Polymorphisms in iron homeostasis genes and urinary cadmium concentrations among nonsmoking women in Argentina and Bangladesh.

BACKGROUND: Cadmium (Cd) is a human toxicant and carcinogen. Genetic variation might affect long-term accumulation. Cd is absorbed via iron transporters. OBJECTIVES: We evaluated the impact of iron homeostasis genes [divalent metal transporter 1 (SLC11A2), transferrin (TF), transferrin receptors (TFR2 and TFRC), and ferroportin (SLC40A1)] on Cd accumulation. METHODS: Subjects were nonsmoking women living in the Argentinean Andes [n = 172; median urinary Cd (U-Cd) = 0.24 µg/L] and Bangladesh (n = 359; U-Cd = 0.54 µg/L) with Cd exposure mainly from food. Concentrations of U-Cd and Cd in whole blood or in erythrocytes (Ery-Cd) were measured by inductively coupled plasma mass spectrometry. Fifty polymorphisms were genotyped by Sequenom. Gene expression was measured in whole blood (n = 72) with Illumina DirectHyb HumanHT-12 v4.0. RESULTS: TFRC rs3804141 was consistently associated with U-Cd. In the Andean women, mean U-Cd concentrations were 22% (95% CI: -2, 51%), and they were 56% (95% CI: 10, 120%) higher in women with GA and AA genotypes, respectively, relative to women with the GG genotype. In the Bangladeshi women, mean U-Cd concentrations were 22% (95% CI: 1, 48%), and they were 58% (95% CI: -3, 157%) higher in women with GA and AA versus GG genotype, respectively [adjusted for age and plasma ferritin in both groups; ptrend = 0.006 (Andes) and 0.009 (Bangladesh)]. TFRC expression in blood was negatively correlated with plasma ferritin (rS = -0.33, p = 0.006), and positively correlated with Ery-Cd (significant at ferritin concentrations of < 30 µg/L only, rS = 0.40, p = 0.046). Rs3804141 did not modify these associations or predict TFRC expression. Cd was not consistently associated with any of the other polymorphisms evaluated. CONCLUSIONS: One TFRC polymorphism was associated with urine Cd concentration, a marker of Cd accumulation in the kidney, in two very different populations. The consistency of the findings supports the possibility of a causal association.

End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden.

BACKGROUND: Cadmium (Cd), lead (Pb), and mercury (Hg) cause toxicological renal effects, but the clinical relevance at low-level exposures in general populations is unclear. The objective of this study is to assess the risk of developing end-stage renal disease in relation to Cd, Pb, and Hg exposure. METHODS: A total of 118 cases who later in life developed end-stage renal disease, and 378 matched (sex, age, area, and time of blood sampling) referents were identified among participants in two population-based prospective cohorts (130,000 individuals). Cd, Pb, and Hg concentrations were determined in prospectively collected samples. RESULTS: Erythrocyte lead was associated with an increased risk of developing end-stage renal disease (mean in cases 76 µg/L; odds ratio (OR) 1.54 for an interquartile range increase, 95% confidence interval (CI) 1.18-2.00), while erythrocyte mercury was negatively associated (2.4 µg/L; OR 0.75 for an interquartile range increase, CI 0.56-0.99). For erythrocyte cadmium, the OR of developing end-stage renal disease was 1.15 for an interquartile range increase (CI 0.99-1.34; mean Ery-Cd among cases: 1.3 µg/L). The associations for erythrocyte lead and erythrocyte mercury, but not for erythrocyte cadmium, remained after adjusting for the other two metals, smoking, BMI, diabetes, and hypertension. Gender-specific analyses showed that men carried almost all of the erythrocyte lead and erythrocyte cadmium associated risks. CONCLUSIONS: Erythrocyte lead is associated with end-stage renal disease but further studies are needed to evaluate causality. Gender-specific analyses suggest potential differences in susceptibility or in exposure biomarker reliability.

Exposure-response relationships in work-related musculoskeletal disorders in elbows and hands - A synthesis of group-level data on exposure and response obtained using uniform methods of data collection.

There is a serious lack of quantitative data regarding exposure-response relationships between occupational risk factors and musculoskeletal elbow and hand disorders. This paper explores such relationships in group-level data from our earlier cross-sectional studies. Prevalence of complaints (Nordic Questionnaire) and diagnoses (physical examination) were recorded in 19 groups of female workers (1891 individuals), and 8 groups of male workers (761 individuals), with highly similar work tasks within each group. Linear regression was performed on the group means of wrist postures and angular velocity (obtained by electrogoniometers), as well as muscular load (obtained using electromyography), recorded in representative sub-samples, and psychosocial exposure (Job Content Questionnaire). To tackle within-group variations in physical exposure, sensitivity analyses were performed by bootstrapping simulations, rendering confidence intervals. The sex-adjusted slope of the regression line (ß) for wrist angular velocity vs. complaints during the past 7 days was 0.6%/(°/s), (95% CI 0.3-0.9), and for carpal tunnel syndrome (CTS) 0.2%/(°/s), (0.1-0.3). For palmar flexion, p50, ß over the past 7 days was 0.8%/° (0.4-1.2); for CTS 0.3%/° (0.1-0.5); ß for muscular activity p90: 0.9%/%MVE (0.3-1.6), and 0.3%/%MVE (-0.03-0.6) respectively and finally ß for muscular rest: -1.2%/%time (-2.4-0.03) and -0.5%/%time (-0.9 to -0.01). Relationships were also demonstrated for low job control, job strain and isostrain. Women exhibited a higher prevalence of complaints than men. In conclusion, we have established quantitative exposure-response relationships between physical work load and elbow/hand disorders. Wrist angular velocity was the most consistent risk factor.

Polymorphisms in genes encoding potential mercury transporters and urine mercury concentrations in populations exposed to mercury vapor from gold mining.

BACKGROUND: Elemental mercury (Hg0) is widely used in small-scale gold mining. Persons working or living in mining areas have high urinary concentrations of Hg (U-Hg). Differences in genes encoding potential Hg-transporters may affect uptake and elimination of Hg. OBJECTIVE: We aimed to identify single nucleotide polymorphisms (SNPs) in Hg-transporter genes that modify U-Hg. METHODS: Men and women (1,017) from Indonesia, the Philippines, Tanzania, and Zimbabwe were classified either as controls (no Hg exposure from gold mining) or as having low (living in a gold-mining area) or high exposure (working as gold miners). U-Hg was analyzed by cold-vapor atomic absorption spectrometry. Eighteen SNPs in eight Hg-transporter genes were analyzed. RESULTS: U-Hg concentrations were higher among ABCC2/MRP2 rs1885301 A-allele carriers than among GG homozygotes in all populations, though differences were not statistically significant in most cases. MRP2 SNPs showed particularly strong associations with U-Hg in the subgroup with highest exposure (miners in Zimbabwe), whereas rs1885301 A-allele carriers had higher U-Hg than GG homozygotes [geometric mean (GM): 36.4 µg/g creatinine vs. 21.9; p = 0.027], rs2273697 GG homozygotes had higher U-Hg than A-allele carriers (GM: 37.4 vs. 16.7; p = 0.001), and rs717620 A-allele carriers had higher U-Hg than GG homozygotes (GM: 83 vs. 28; p = 0.084). The SLC7A5/LAT1 rs33916661 GG genotype was associated with higher U-Hg in all populations (statistically significant for all Tanzanians combined). SNPs in SLC22A6/OAT1 (rs4149170) and SLC22A8/OAT3 (rs4149182) were associated with U-Hg mainly in the Tanzanian study groups. CONCLUSIONS: SNPs in putative Hg-transporter genes may influence U-Hg concentrations.

Mercury in serum predicts low risk of death and myocardial infarction in Gothenburg women.

PURPOSE: Markers of mercury (Hg) exposure have shown both positive and negative associations with cardiovascular disease (CVD). We assessed the association between serum Hg (S-Hg) and risk of cardiovascular disease in a prospective population-based cohort, with attention to the roles of dental health and fish consumption. METHODS: Total mortality, as well as morbidity and mortality from acute myocardial infarction (AMI) and stroke, was followed up for 32 years in 1,391 women (initially age 38-60), in relation to S-Hg at baseline, using Cox regression models. Potential confounders (age, socioeconomic status, serum lipids, alcohol consumption, dental health, smoking, hypertension, waist-hip ratio, and diabetes) and other covariates (e.g., fish consumption) were also considered. RESULTS: Hazard ratios (HR) adjusted only for age showed strong inverse associations between baseline S-Hg and total mortality [highest quartile: hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.59-0.97], incident AMI (HR 0.56; CI 0.34-0.93), and fatal AMI (HR 0.31; CI 0.15-0.66). Adjustment for potential confounding factors, especially dental health, had a strong impact on the risk estimates, and after adjustment, only the reduced risk of fatal AMI remained statistically significant. CONCLUSIONS: There was a strong inverse association between Hg exposure and CVD. Likely, reasons are confounding with good dental health (also correlated with the number of amalgam fillings in these age groups) and/or fish consumption. The results suggest potential effects of dental health and/or fish consumption on CVD that deserve attention in preventive medicine.

Myocardial infarction in relation to mercury and fatty acids from fish: a risk-benefit analysis based on pooled Finnish and Swedish data in men.

BACKGROUND: Exposure to methylmercury from fish has been associated with increased risk of myocardial infarction (MI) in some studies. At the same time, marine n-3 (omega-3) PUFAs are an inherent constituent of fish and are regarded as beneficial. To our knowledge, no risk-benefit model on the basis of data on methylmercury, PUFA, and MI risk has yet been presented. OBJECTIVE: The objective of this study was to describe how exposure to both marine n-3 PUFAs and methylmercury relates to MI risk by using data from Finland and Sweden. DESIGN: We used matched case-control sets from Sweden and Finland that were nested in population-based, prospective cohort studies. We included 361 men with MI from Sweden and 211 men with MI from Finland. MI risk was estimated in a logistic regression model with the amount of mercury in hair (hair-Hg) and concentrations of n-3 PUFAs (EPA and DHA) in serum (S-PUFA) as independent variables. RESULTS: The median hair-Hg was 0.57 µg/g in Swedish and 1.32 µg/g in Finnish control subjects, whereas the percentage of S-PUFA was 4.21% and 3.83%, respectively. In combined analysis, hair-Hg was associated with higher (P = 0.005) and S-PUFA with lower (P = 0.011) MI risk. Our model indicated that even a small change in fish consumption (ie, by increasing S-PUFA by 1%) would prevent 7% of MIs, despite a small increase in mercury exposure. However, at a high hair-Hg, the modeled beneficial effect of PUFA on MI risk was counteracted by methylmercury. CONCLUSIONS: Exposure to methylmercury was associated with increased risk of MI, and higher S-PUFA concentrations were associated with decreased risk of MI. Thus, MI risk may be reduced by the consumption of fish high in PUFAs and low in methylmercury.