Natalia Pawlas

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.

Modification by the genes ALAD and VDR of lead-induced cognitive effects in children.

Lead has negative effect on cognitive functions in children. However, individuals differ in susceptibility. One possible explanation is a genetic predisposition. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity, but information regarding the central nervous system is very limited. The aim of the study was to determine whether ALAD and VDR polymorphisms modify blood lead (B-Pb), and the association between B-Pb and cognitive function (IQ) in children. In 2007-2010 a cohort of 175 children (age 6-10years, mean 7.8) was recruited in Southern Poland, tested for IQ (Wechsler intelligence scale) and analyzed for B-Pb (range 9.0-221; mean 46.6μg/L), ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI) polymorphisms. ALAD or VDR genotypes were not associated with B-Pb. B-Pb was non-significantly negatively associated with full scale IQ (r(S)=-0.11; P=0.14), and significantly with performance subscale results (r(S)=-0.19; P=0.01). The ALAD RsaI polymorphism modified the relationship between full scale IQ and B-Pb: RsaI T carriers had a steeper slope compared to CC homozygote carriers (β coefficient -0.06 vs 0.32, respectively, P for interaction <0.001, adjusted for the childs age, mothers education and family income). This means that with increasing B-Pb with 1μg/L, T carriers demonstrate 0.06 score lower IQ. For the VDR BsmI, B carriers had a steeper slope than the bb homozygotes carriers (β coefficient -0.08 vs 0.16, respectively, P for interaction=0.001), and similar effect was found for TaqI t carriers vs TT homozygotes (P for interaction=0.02). For ALAD MspI and VDR FokI there was no significant modification. The ALAD RsaI, VDR BsmI and TaqI polymorphisms modified the relationship between IQ and B-Pb. Hence, there is a fraction of the population, which is particularly sensitive to lead neurotoxicity.

The effect of occupational lead exposure on blood levels of zinc, iron, copper, selenium and related proteins.

The study objective was to evaluate the effect of occupational lead exposure on blood concentrations of zinc, iron, copper, selenium and proteins related to them, such as transferrin, caeruloplasmin and haptoglobin. The examined group consisted of 192 healthy male employees of zinc–lead works. By the degree of lead exposure, the exposed group was subdivided into three subgroups. The control group was composed of 73 healthy male administrative workers. The markers of lead exposure (blood levels of lead and zinc protoporphyrin) were significantly elevated in the exposed group compared with the control group. Additionally, concentrations of copper and caeruloplasmin were raised. The significant increase in haptoglobin level was observed only in the low exposure group. Selenium levels were significantly decreased, whereas iron, zinc and transferrin levels were unchanged in the exposed group compared with the control group. There were positive correlations between the lead toxicity parameters and the copper and caeruloplasmin levels. In conclusion, the effect of occupational exposure to lead on the metabolism of trace metals appears to be limited. However, significant associations between lead exposure and levels of copper and selenium were shown. Changed levels of positive acute-phase proteins, such as caeruloplasmin and haptoglobin, were also observed.

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.

A multicenter study on the audiometric findings of styrene-exposed workers

Abstract Objective: The objective of this study was to evaluate hearing loss among workers exposed to styrene, alone or with noise. Design: This cross-sectional study was conducted as part of NoiseChem, a European Commission 5th Framework Programme research project, by occupational health institutes in Finland, Sweden, and Poland. Study sample: Participants’ ages ranged from 18–72 years (n = 1620 workers). Participants exposed to styrene, alone or with noise, were from reinforced fiberglass products manufacturing plants (n = 862). Comparison groups were comprised of workers noise-exposed (n = 400) or controls (n = 358). Current styrene exposures ranged from 0 to 309 mg/m3, while mean current noise levels ranged from 70–84 dB(A). Hearing thresholds of styrene-exposed participants were compared with Annexes A and B from 2. Results: The audiometric thresholds of styrene exposed workers were significantly poorer than those in published standards. Age, gender, and styrene exposure met the significance level criterion in the multiple logistic regression for the binary outcome ‘hearing loss’ (P = 0.0000). Exposure to noise (<85 dBA p = 0.0001; ≥85 dB(A) p = 0.0192) interacted significantly with styrene exposure. Conclusions: Occupational exposure to styrene is a risk factor for hearing loss, and styrene-exposed workers should be included in hearing loss prevention programs. Sumario Objetivo: El objetivo de este estudio fue evaluar la pérdida auditiva en trabajadores expuestos a estireno, aisladamente o con ruido. Diseño: Se realizó este estudio transversal como parte del NoiseChem, Comisión Europea del 5°. Proyecto Marco de investigación, en institutos de salud ocupacional de Finlandia, Suecia y Polonia. Muestra de estudio: La edad de los participantes fue de 18–72 a os (N = 1,620 trabajadores). Los trabajadores (n = 862) estuvieron expuestos a estireno, solo o con ruido, en plantas de fabricación de productos de fibra de vidrio reforzada. Los grupos de comparación fueron trabajadores expuestos a ruido (n = 400) y los de un grupo control (n = 358). Las exposiciones reales a estireno variaron de 0 a 309 mg/m3, mientras que los niveles reales de ruido, variaron de 80–84 dB(A). Se compararon los niveles de audición de los participantes expuestos a estireno con los de los anexos A y B de 2. Resultados: Los umbrales audiométricos de los trabajadores expuestos a estireno, fueron significativamente más pobres que los que se han publicado como estándar. La edad, el género y la exposición a estireno, cubrieron los criterios de niveles de significatividad de la regresíón logística múltiple para los resultados binarios de la “perdida auditiva” (P = 0.0000). La exposición a ruido (<85 dB(A) p = 0.0001; ≥85 dB(A) p = 0.0192) interactu significativamente con la exposición a estireno. Conclusiones: La exposición ocupacional a estireno es un factor de riesgo de pérdida auditiva por lo que los trabajadores expuestos a estireno deben ser incluidos en programas de prevención de pérdidas auditivas.

Effect of treatment with N-acetylcysteine on non-enzymatic antioxidant reserves and lipid peroxidation in workers exposed to lead

There are no published studies examining the effects of N-acetylcysteine (NAC) administration on the non-enzymatic defence systems in humans exposed to lead. In view of this, it was decided to measure the levels of uric acid (UA), albumin, bilirubin and alpha-tocopherol before and after treatment with NAC. An estimation was also made of the degree of oxidative stress by measuring the ferric reducing ability of plasma (FRAP), the levels of conjugated dienes (CD) and lipid hydroperoxides (LHP). Male employees who worked with lead were randomized into two groups. The first group included workers who were not administered any drugs (n=49), while the second group (n=122) consisted of workers who were treated with NAC at three different doses (200 mg, 400 mg and 800 mg) for 12 weeks. The administration of NAC (400 mg, 800 mg) resulted in significant decreases in the LHP levels. Similarly, a strong tendency toward lower levels of CD was observed in the same groups. The UA levels were significantly lower only in the group receiving the 200 mg dose of NAC. However, the alpha-tocopherol levels were significantly elevated after treatment with NAC (400 mg, 800 mg). NAC administration did not significantly affect the levels of bilirubin and albumin, but a tendency toward higher values was observed for FRAP. NAC reduced the extent of lipid peroxidation in a dose-dependent manner. Elevated concentrations of alpha-tocopherol may have enhanced the beneficial effects of NAC. Treatment with NAC may contribute to the restoration of non-enzymatic antioxidant reserves when administered to lead-exposed workers.

Effects of chronic exposure to lead, cadmium, and manganese mixtures on oxidative stress in rat liver and heart

Abstract The aim of this study was to assess the effects of chronic combined exposure to low, environmental doses of Cd, Pb, and Mn on oxidative stress in the liver and heart of rats and on their liver function parameters. Male Wistar rats were divided randomly into eight groups. For nine months controls were receiving drinking water alone, whereas the exposed groups were receiving drinking water with Pb (0.2 mg L-1), Cd (1 mg L-1), and Mn (2 mg L-1) alone or in combinations. Malondialdehyde (MDA) significantly increased in both heart and liver of the animals after combined exposure to metals. Heart MDA correlated with blood Cd, Pb, and Mn and liver MDA with blood Cd. Aspartate aminotransferase (AST) activity and bilirubin concentration also increased significantly in the animal group exposed to all three metals and correlated positively with blood Cd, Pb, and Mn. Our study has confirmed the synergistic effect of the Cd, Mn, and Pb combination on the increase in heart MDA. A similar synergy was observed for Pb+Mn in the increase of serum alanine aminotransferase (ALT) activity as an indicator of liver function. Cilj je ovog istraživanja bio ocijeniti učinke kronične izloženosti kombinaciji Cd, Pb i Mn u niskim dozama kakve su u okolišu na oksidativni stres u jetrima i srcu štakora te na pokazatelje jetrene funkcije. U tu smo svrhu mužjake Wistar štakora nasumce podijelili u osam skupina, od kojih je kontrolna pila čistu vodu, a izložene skupine vodu pomiješanu s olovom (0,2 mg L-1), kadmijem (1 mg L-1) i manganom (2 mg L-1), zasebno ili u kombinacijama. Koncentracija malondialdehida (MDA) značajno se povećala u oba organa životinja izloženih kombinacijama metala. Srčani MDA korelirao je s razinama kadmija, olova i mangana u krvi, a jetreni MDA s razinom kadmija u krvi. Aktivnost aspartat aminotransferaza (AST) i koncentracije bilirubina također su bile značajno povišene u skupini izloženoj svim trima metalima te su korelirale s razinama kadmija, olova i mangana u krvi. Rezultati istraživanja potvrdili su da zajedno ova tri metala djeluju na povećanje MDA u srcu. Slična je sinergija zamijećena i između olova i mangana s obzirom na povećanje razine alanin aminotransferaze (ALT) u serumu, koji je pokazatelj jetrene funkcije.

Oxidative DNA damage and oxidative stress in lead-exposed workers.

There are many discrepancies among the results of studies on the genotoxicity of lead. The aim of the study was to explore lead-induced DNA damage, including oxidative damage, in relation to oxidative stress intensity parameters and the antioxidant defense system in human leukocytes. The study population consisted of 100 male workers exposed to lead. According to the blood lead (PbB) levels, they were divided into the following three subgroups: a group with PbB of 20–35 μg/dL (low exposure to lead (LE) group), a group with a PbB of 35–50 µg/dL (medium exposure to lead (ME) group), and a group with a PbB of >50 μg/dL (high exposure to lead (HE) group). The control group consisted of 42 healthy males environmentally exposed to lead (PbB < 10 μg/dL). A comet assay was used to measure the DNA damage in leukocytes. We measured the activity of superoxide dismutase (SOD), catalase, glutathione reductase (GR), glucose-6-phosphate dehydrogenase (G6PD), and glutathione-S-transferase (GST) as well as the concentration of malondialdehyde (MDA), and the value of the total antioxidant capacity. The level of PbB was significantly higher in the examined subgroups than in the control group. The percentage of DNA in the tail was significantly higher in the LE, ME, and HE subgroups than in the control group by 10% (p = 0.001), 15% (p < 0.001), and 20% (p < 0.001), respectively. The activity of GR was significantly lower in the LE and ME subgroups than in the control group by 25% (p = 0.007) and 17% (p = 0.028), respectively. The activity of G6PD was significantly lower in the ME subgroup by 25% (p = 0.022), whereas the activity of GST was significantly higher in the HE subgroup by 101% (p = 0.001) than in the control group. Similarly, the activity of SOD was significantly higher in the LE and ME subgroups by 48% (p = 0.026) and 34% (p = 0.002), respectively. The concentration of MDA was significantly higher in the LE, ME, and HE subgroups than in the control group by 43% (p = 0.016), 57% (p < 0.001), and 108% (p < 0.001), respectively. Occupational lead exposure induces DNA damage, including oxidative damage, in human leukocytes. The increase in DNA damage was accompanied by an elevated intensity of oxidative stress.

Glutathione, glutathione-related enzymes, and oxidative stress in individuals with subacute occupational exposure to lead

The aim of the study was to investigate the influence of subacute exposure to lead on the glutathione-related antioxidant defense and oxidative stress parameters in 36 males occupationally exposed to lead for 40±3.2days. Blood lead level in the examined population increased significantly by 359% due to lead exposure. Simultaneously, erythrocyte glutathione level decreased by 16%, whereas the activity of glutathione-6-phosphate dehydrogenase in erythrocytes and leukocytes decreased by 28% and 10%, respectively. Similarly, the activity of glutathione-S-transferase in erythrocytes decreased by 45%. However, the activity of glutathione reductase in erythrocytes and leukocytes increased by 26% and 6%, respectively, whereas the total oxidant status value in leukocytes increased by 37%. Subacute exposure to lead results in glutathione pool depletion and accumulation of lipid peroxidation products; however, it does not cause DNA damage. Besides, subacute exposure to lead modifies the activity of glutathione-related enzymes.

Effect of N-acetylcysteine administration on homocysteine level, oxidative damage to proteins, and levels of iron (Fe) and Fe-related proteins in lead-exposed workers

N-Acetylcysteine (NAC) could be included in protocols designed for the treatment of lead toxicity. Therefore, in this study, we decided to investigate the influence of NAC administration on homocysteine (Hcy) levels, oxidative damage to proteins, and the levels of iron (Fe), transferrin (TRF), and haptoglobin (HPG) in lead (Pb)-exposed workers. The examined population (n = 171) was composed of male employees who worked with Pb. They were randomized into four groups. Workers who were not administered any antioxidants, drugs, vitamins, or dietary supplements were classified as the reference group (n = 49). The remaining three groups consisted of workers who were treated orally with NAC at three different doses (1 × 200, 2 × 200, or 2 × 400 mg) for 12 weeks. After the treatment, blood Pb levels significantly decreased in the groups receiving NAC compared with the reference group. The protein concentration was not affected by NAC administration. In contrast, Hcy levels significantly decreased or showed a strong tendency toward lower values depending on the NAC dose. Levels of the protein carbonyl groups were significantly decreased in all of the groups receiving NAC. Conversely, glutamate dehydrogenase activity was significantly elevated in all of the groups receiving NAC, while the level of protein thiol groups was significantly elevated only in the group receiving 200 mg of NAC. Treatment with NAC did not significantly affect Fe and TRF levels, whereas HPG levels showed a tendency toward lower values. Treatment with NAC normalized the level of Hcy and decreased oxidative stress as measured by the protein carbonyl content; this effect occurred in a dose-dependent manner. Moreover, small doses of NAC elevated the levels of protein thiol groups. Therefore, NAC could be introduced as an alternative therapy for chronic Pb toxicity in humans.