Florencia Harari

Blood cadmium, mercury, and lead in children: an international comparison of cities in six European countries, and China, Ecuador, and Morocco.

Childrens blood-lead concentration (B-Pb) is well studied, but little is known about cadmium (B-Cd) and mercury (B-Hg), in particular for central Europe. Such information is necessary for risk assessment and management. Therefore, we here describe and compare B-Pb, B-Cd and B-Hg in children in six European, and three non-European cities, and identify determinants of these exposures. About 50 school children (7-14 years) from each city were recruited (totally 433) in 2007-2008. Interview and questionnaire data were obtained. A blood sample was analyzed: only two laboratories with strict quality control were used. The European cities showed only minor differences for B-Cd (geometric means 0.11-0.17 μg/L) and B-Pb (14-20 μg/L), but larger for B-Hg (0.12-0.94 μg/L). Corresponding means for the non-European countries were 0.21-0.26, 32-71, and 0.3-3.2 μg/L, respectively. For B-Cd in European samples, traffic intensity close to home was a statistically significant determinant, for B-Hg fish consumption and amalgam fillings, and for B-Pb sex (boys higher). This study shows that European city childrens B-Cd and B-Pb vary only little between countries; B-Hg differs considerably, due to varying tooth restoration practices and fish intake. Traffic intensity seemed to be a determinant for B-Cd. The metal concentrations were low from a risk perspective but the chosen non-European cities showed higher concentrations than the cities in Europe.

Exposure and toxic effects of elemental mercury in gold-mining activities in Ecuador

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.

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

ObjectivesThe 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 MethodsAbout 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.ResultsBetween 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.ConclusionsThe 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.

Impact of Ficoll density gradient centrifugation on major and trace element concentrations in erythrocytes and blood plasma.

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.

Alkali dilution of blood samples for high throughput ICP-MS analysis-comparison with acid digestion.

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.

Environmental exposure to lithium during pregnancy and fetal size: A longitudinal study in the Argentinean Andes

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.

Early-life exposure to lithium and boron from drinking water.

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.

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.

Exposure to Inorganic Arsenic Is Associated with Increased Mitochondrial DNA Copy Number and Longer Telomere Length in Peripheral Blood

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.

Boron exposure through drinking water during pregnancy and birth size

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.