Effect of the delta-aminolevulinic acid dehydratase gene polymorphism on renal and neurobehavioral function in workers exposed to lead in China

Effects of delta-aminolevulinic acid dehydratase (ALAD) polymorphisms on the renal and neurobehavioral functions were investigated in Chinese workers from a storage battery plant exposed to inorganic lead. Blood and urine were collected from each worker to determine the ALAD genotypes, blood lead levels (PbB), urinary β2-MG and urinary NAG activity. The World Health Organization Neurobehavioral Core Test Battery (WHO-NCTB) was used. Of the 135 lead workers tested for ALAD genotype, 126 were ALAD1-1, 9 were ALAD1-2 but none were ALAD2-2. The gene frequencies of ALADl-1 and ALADl-2 were 93.33% and 6.67%, respectively. The workers with ALAD1-2 genotype had significantly higher concentrations of PbB (62.52 µg/dl vs. 41.02 µg/dl), urinary NAG (22.01 U/gCr vs. 13.49 U/gCr), urinary β2-MG (194.98 μg/gCr vs. 112.88 μg/gCr), and digit span backward (DSB) score (6.67 vs. 5.33) than those of ALAD1-1 genotype. Urinary NAG of ALAD1-2 genotype carriers was significantly higher than that of ALAD1-1 genotype under the same blood lead level (b_i 0.75 vs. b_i 0.29). Interaction between PbB and ALAD genotypes has a significant influence on NAG (P = 0.02) and β₂-MG (P = 0.01). It is postulated that the workers with the ALAD2 allele appear to be more susceptible to the effects of lead on renal injury, whereas neurobehavioral functions in ALAD1 homozygote tend to be more vulnerable.     

Lung cancer risks among lead smelter workers also exposed to arsenic.

Recent publications indicate an increased incidence of lung cancer in non-ferrous smelter workers exposed to lead. The present study provides further data on selected subgroups in one such cohort. The cohort was based on 3979 smelter workers employed for at least 1 year between 1928 and 1979, and also exposed to lead and included in the Blood Lead Register that was started at the smelter in 1950. Two subcohorts were formed from the original cohort. One consists of 710 workers employed at the lead departments (Lead subcohort 1), and the other of 383 workers employed at the lead departments (Lead subcohort 2), but never at other works where an excess lung cancer risk was previously identified. Standardized Cancer Incidence Rates (SIR) 1958-1987 were calculated relative to county rates. In the subcohorts, arsenic exposure in lung cancer cases was assessed in detail based on occupational hygiene information from the company. Lung cancer incidence was raised in both subcohorts (Lead subcohort 1: SIR 2.4; 95% CI 1.2-4.5; Lead subcohort 2: SIR 3.6; 95% CI 1.2-8.3). Total cancer incidence in the cohorts was not increased. A detailed study of arsenic exposure in the 10 lung cancer cases in these two subcohorts revealed that all but one of these cases had a significant exposure also to arsenic. An elevated incidence of lung cancer was observed in smelter workers exposed to lead. However, considerable arsenic exposure also occurred in a majority of the lung cancer cases in the investigated subcohorts. In this multifactorial exposure situation it has not been possible to separate the carcinogenic effects of lead and arsenic, but a possible interaction between these metals may be involved in explaining the carcinogenic risks.     

Immune parameters in female workers exposed to urban pollutants

Urban outside workers, such as traffic police, are daily exposed to air pollutants and psychosocial stressors: for these workers, the working environment corresponds to the living environment of the general population. Studies in the literature have shown that immune parameters could be affected by chronic exposure to various chemical pollutants. The aim of this study is to evaluate whether occupational exposure to urban pollutants can cause alterations in NK, IL-2, IFN-gamma and C3 plasma levels in female traffic police compared to a control group. After excluding subjects with the principal confounding factors, 86 female traffic police and 87 controls were matched by age, years of police work and habitual alcohol consumption. The distribution of NK values in female traffic police and controls was significantly different (p=0.000); NK values above the upper limit of the normal laboratory range were observed in 23 female traffic police and in 2 controls (p=0.000). IL-2 mean levels were higher in traffic police compared to controls, but the difference was not significant. The mean and the distribution of IFN-gamma values in female traffic police and controls were not different. C3 mean levels were higher in female traffic police versus controls, but the difference was not significant. Considering that the subjects with the principal confounding factors were excluded from the study and that female traffic police and controls were matched by the above-mentioned variables, our results suggest that chronic occupational exposure to low doses of chemical stressors, which may interact with and add to psychosocial ones, can affect both innate and adaptative immunity.     

Distribution of cadmium,lead and zinc in lung,liver and kidney in long-term exposed smelter workers

Increased mortality due to various malignancies is reported from long-term exposed, non-ferrous smelter workers. In the present study the post-mortem distribution of cadmium, lead and zinc in lung, liver and kidney is reported and related to exposure and mortality.The study involved 86 male copper smelter workers who died after April 1975. Lung samples were taken from all workers and liver and kidney samples were taken from about one-quarter of the workers. Two control groups were used. The exposed workers were divided into six groups based upon diagnoses in medical records and autopsy protocols.Lead and zinc were analyzed by atomic absorption spectrophotometry and cadmium by neutron activation analysis. For the skewly distributed tissue levels, non-parametric statistical processing was used.Of the workers, 53% died from cardiovascular diseases and 30% from malignancies (8% from lung cancer). Cardiovascular diseases predominated in the two control groups: about 75 and 100%, respectively.Lung and liver cadmium concentrations were significantly higher in the lung cancer group of smelter workers than in the other groups of smelter workers (p < 0.05) and rural controls (p < 0.01). Cadmium in kidney, and lead in lung and liver were significantly higher (p < 0.03) in the lung cancer group than in rural controls, but did not differ from that of the other workers. Zinc in lung, liver and kidney did not differ between exposed workers and controls. Rather strong Spearman rank-order correlation coefficients were found between the cadmium content of lung, liver and kidney tissue, especially in non-smoking smelter workers and rural controls. Smoking was more common in the lung cancer group than in the total group of smelter workers. Cadmium levels in the lungs of exposed workers were significantly higher (p < 0.001) in smokers than in both ex-smokers and non-smokers.Earlier studies of the same workers gave significantly lower selenium levels in lung tissue compared with other groups of smelter workers and controls. As other carcinogenic substances are present in the working environment, e.g. arsenic, chromium and benzo[a]-pyrene, the specific effect of cadmium in the development of lung cancer cannot be evaluated at present.     

Proteomic analysis of serum of workers occupationally exposed to arsenic, cadmium, and lead for biomarker research: A preliminary study

The main factor of environmental contamination is the presence of the heavy metals lead, cadmium, and arsenic. The aim of serum protein profile analysis of people chronically exposed to heavy metals is to find protein markers of early pathological changes. The study was conducted in a group of 389 healthy men working in copper foundry and 45 age-matched non-exposed healthy men. Toxicological test samples included whole blood, serum, and urine. Thirty-seven clinical parameters were measured. Based on the parameters values of the healthy volunteers, the centroid in 37-dimensional space was calculated. The individuals in the metal-exposed and control groups were ordered based on the Euclidean distance from the centroid defined by the first component according to Principal Component Analysis (PCA). Serum samples of two individuals, one from the control and one from the metal-exposed group, were chosen for proteomic analysis. In optimized conditions of two-dimensional gel electrophoresis (2-DE), two protein maps were obtained representing both groups. Twenty-eight corresponding protein spots from both protein maps were chosen and identified based on PDQuest analysis and the SWISS-2DPAGE database. From a panel of six proteins with differences in expression greater than a factor of two, three potential markers with the highest differences were selected: hemoglobin-spot 26 (pI 7.05, Mw 10.53), unidentified protein-spot 27 (pI 6.73, Mw 10.17), and unidentified protein-spot 25 (pI 5.75, Mw 12.07). Further studies are required to prove so far obtained results. Identified proteins could serve as potential markers of preclinical changes and could be in the future included in biomonitoring of people exposed to heavy metals.     

The longitudinal evaluation of verbal-reasoning in lead workers

Four times during the course of a year, asymptomatic lead workers from the printing industry underwent a series of psychological tests assessing memory, attention, verbal-reasoning and spatial skills. In a syntactic reasoning task, the exposed group were less accurate, tended to be slower on the more complex problems and showed less consistent improvement over the year. An examination of subjects with changing blood-lead levels during the year showed that, within the exposed group, those with rising blood-lead levels were less accurate than those whose blood-leads fell or remained constant. This may indicate that effects of changing blood-lead concentrations depend upon overall level of exposure.     

Sweat lead levels in persons with high blood lead levels: lead in sweat of lead workers in the tropics

Samples of blood, sweat and urine were collected from eight control subjects and 19 lead workers in a battery manufacturing factory in the tropics. Sweat samples were collected while workers cycled on a bicycle ergometer at room temperature (27-31 degrees C). All samples were analysed by atomic absorption spectrophotometry. Workers with blood lead levels of 13-36 micrograms dl-1 had sweat levels of 72-256 micrograms l-1 and urinary levels of 28-288 micrograms/g creatinine, while controls had levels of 9-12.2 micrograms dl-1, 9-30 micrograms l-1 and 9-19.6 microgram/g creatinine, respectively. Estimations of sweat lead in lead workers can be masked by skin contamination.     

Luteinizing hormone (LH) levels in male workers exposed to urban stressors

The aim of the study is to evaluate if occupational exposure to urban stressors could cause alterations in luteinizing hormone (LH) plasma levels in male traffic policemen vs. administrative staff of Municipal Police.After excluding the subjects with the main confounding factors, male traffic police and administrative staff of Municipal Police were matched by age, working life, body mass index (BMI), alcohol drinking habit, cigarette smoking habit and habitual consumption of Italian coffee.In 166 male traffic police mean LH values were significantly higher compared to 166 male administrative employees. The distribution of LH values in traffic police and in administrative employees was statistically significant.Our results suggest that recent exposure to urban stressors (chemical, physical and psycho-social) can alter the plasma concentration of LH. In agreement with our previous research, levels of plasma LH may be used as early biological markers, valuable for the group, used in occupational set before the appearance of the disease.     

Risk of birth defects in a population exposed to environmental lead pollution.

To investigate the relation between environmental lead and risk of birth defects in humans, we examined the prevalence at birth of congenital anomalies in an industrial area of northern Italy heavily polluted with lead. Through a population-based registry of birth defects, we identified anomalies diagnosed during three consecutive periods characterized by decreasing environmental lead exposure, 1982-1986, 1987-1990 and 1991-1995. In the lead-polluted area, we observed an excess risk of cardiovascular defects which decreased from 2.59 [95% confidence interval (CI) 1.68-3.82] in the first period to 1.18 (95% CI 0.62-2.06) and 0.97 (95% CI 0.57-1.54) in the subsequent periods. We also found an excess risk of oral clefts and musculoskeletal anomalies, with decreasing trends over time. We could not identify homogeneous patterns of temporal variation for other congenital anomalies, neither did we detect cases of neural tube defects. These results appear to support an association between severe parental lead exposure and specific birth defects.     

Morphology of enamel in primary teeth from children in Thailand exposed to environmental lead

Lead is one of the major environmental pollutants and a health risk. Dental hard tissues have a capacity to accumulate lead from the environment. Eighty exfoliated primary teeth were collected from children residing around a shipyard area in southern Thailand, known for its lead contamination. The morphology of the enamel was examined by polarized light microscopy (PLM), microradiography (MRG), and scanning electron microscopy (SEM). The specimens derived from two groups of children, one group with high blood levels of lead (57 teeth) and one group having low blood levels of lead (23 teeth). The enamel irrespective of group appeared normal. However, in a majority of the specimens the enamel surface appeared hypomineralized, which was confirmed in SEM. No morphological changes connected to lead in blood could be found. The hypomineralized surface zone could possibly be attributed to an acid oral environment.     

Monocyte-macrophage system and polymorphonuclear leukocytes in workers exposed to low levels of metallic mercury

Our previous research (Soleo L, Vacca A, Vimercati L et al. Occup Environ Med 1997;54:437-442) showed a reduction in tumor necrosis factor-alpha (TNF-alpha) serum levels in workers with prolonged exposure to low doses of inorganic mercury, suggesting an in vivo functional defect of the monocyte-macrophage system. On this basis, here we wondered whether workers exposed to lower doses of metallic mercury displayed possible changes in the monocyte-macrophage system. In this particular cohort of workers, we also sought for the effects of the exposure on the polymorphonuclear leukocytes (PMNL) chemotaxis. The monocyte-macrophage system and the natural killer (NK) cells were examined in 19 exposed workers and in 25 unexposed workers, as the control group (controls). Specifically, the circulating monocyte-macrophage cells and their CD13, CD15 and CD33 subsets, serum cytokines (IL-8, GM-CSF and TNF-alpha) and the NK cells were analyzed. In seven exposed and seven controls randomly chosen workers the PMNL chemotaxis was also assessed. The selected indicator of mercury exposure were the levels of mercury in the urine (U-Hg), that was significantly higher in exposed workers than the controls (9.7 +/- 5.5 microg/l and 2.4 +/- 1.2 microg/l, respectively). None of the exposed workers had shown signs of either acute or chronic inorganic mercury toxicity or any form of hypersensitivity. Several immunological variables tested, monocyte-macrophage cells and their subsets, NK cells and serum cytokines overlapped between the exposed and the control workers. When the workers were considered as a whole (exposed plus controls), no correlation was found between current U-Hg and all immunological parameters. However, when exposed workers were studied separately, an inverse correlation was disclosed between cumulative U-Hg and cells (as percentage) expressing the CD13 (r = -0.599; P = 0.007) and CD15 (r = -0.614; P = 0.005) molecules, and NK cells (r = -0.455; P = 0.05). Moreover, a significant impairment in the PMNL chemotaxis (t = 3.70; P = 0.003) was observed in the exposed workers. The results of our study suggest that the exposure to very low levels of metallic mercury led to subtle impairment of circulating monocyte and NK cells (as percentages) according to the increase in U-Hg levels, as well as of the PMNL chemotactic function in this particular group of workers, even though they remain clinically asymptomatic. Therefore, we suggest that impairment of these parameters provide a sensitive indicator of metallic mercury and other chemical contaminants present in the environment.     

Chemical composition of enamel and dentine in primary teeth in children from Thailand exposed to lead

Enamel and dentine in teeth of children with high blood levels of lead were analyzed by means of secondary ion mass spectrometry (SIMS) and X-ray micro-analyses (XRMA) and compare with teeth from children with low blood levels of lead. The SIMS analysis revealed detectable levels of Pb in dentine close to the pulp. The XRMA analyses could not detect any lead. There were no differences found in lead level in enamel of high lead level exposed teeth from low level exposed. The results confirm that children with high blood levels of lead have an uptake of lead in dentine close to the pulp.     

Observations on the tolerance of the isopod Asellus meridianus Rac. to copper and lead

Asellus meridianus Rac. from sites receiving mine-drainage in the rivers Hayle and Gannel in Cornwall have been shown, by toxicity tests and growth rate experiments to be particularly tolerant to copper and lead. Animals from the Hayle, where there are high concentrations of copper in both waters and sediments but only trace amounts of lead, are tolerant to both copper and lead. Animals from the River Gannel where there are moderately high concentrations of copper and exceptionally high concentrations of lead, are markedly tolerant to only lead. Tolerance to lead was shown to persist in animals from the Gannel F₂ generation which had been cultured in the laboratory.     

Lipid peroxidation and antioxidant status in workers exposed to PCDD/Fs of metal recovery plants

Secondary copper smelters, which primarily utilize the waste materials that contain organic impurities, and the zinc recovery plant, which handles mostly fly ash and slag from the iron and steel industry, are major emission sources of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) in Taiwan. In this study, we compared the levels of erythrocyte glutathione (GSH), erythrocyte superoxide dismutase (SOD) and plasma malondialdehyde (MDA) in workers at a secondary copper smelting plant and a zinc recovery plant who may have been exposed to PCDD/Fs. Though the PCDD/F levels were higher in workers of zinc recovery plant than those of secondary copper smelting plant, no significant difference was found for serum PCDD/F levels between the two kinds of plants. We observed a significant difference in plasma MDA levels between workers at the zinc recovery plant (2.54 microM) and those at the copper smelting plant (1.79 microM). There was and a significant positive correlation between plasma MDA levels and the PCDD/Fs levels. In addition, we observed that the MDA levels were not affected by smoking and exercise status. Therefore, the data suggest that the MDA levels of the metal recovery workers are influenced by their PCDD/F exposure. The erythrocyte SOD activity in workers from the zinc recovery plant was marginally higher than that from the secondary copper plant (196 vs. 146 units/ml, p<0.06). In both plants, large variations in the MDA and SOD levels were found, especially in the high-PCDD/Fs-exposure group, which may be attributed, at least partially, to the differences in smoking status and the number of cigarettes smoked. Overall, our results indicate a higher oxidative stress in workers of the zinc recovery plant than in workers of the secondary copper smelting plant in Taiwan.     

Effects derived from long-term low-level chromium exposure in ferro-alloy metallurgy. Study of absorption and renal function in workers

Ferro-chromium production is based on the use of chromium oxide (III) and it is generally accepted that chromium in this form is not able to cross biological barriers. However, the data on the toxic and carcinogenic effects of hexavalent chromium in man are now firmly established. Some studies have questioned these data, calling for a clarification as to whether exposure to trivalent chromium can also produce human effects, perhaps with different latency time. A study was carried out on the exposure conditions (type and degree) in a ferro-chromium foundry that had been in operation since 1972. The absorption levels in the working population of the foundry, and the possible toxic effects on the kidney have been investigated. A total of 236 workers (142 employed in production departments, 33 office workers and 61 sub-contractor employees) were examined with measurement of the indicators of dose (urinary-chromium) and of effect on the kidney (albumin, retinol binding protein, and renal tubular epithelium antigens in the urine). Environmental hygiene measurements showed relatively low values of total chromium in the air (always less than 0.160 mg/m3). Hexavalent chromium was absent or, if present, at levels below the sensitivity of the analytical method used (0.001 mg/m3). The values of urinary chromium measured at the beginning and at the end of the working day and at the end of the work shift were always less than 5 micrograms/g creatinine, which has been proposed as a biological limit in chromium exposure. However, differences were observed between groups of subjects employed on different jobs, which is indicative of an absorption process varying according to the degree of exposure. The indicators of effect did not reveal any renal impairment, even early, that could be attributed to the toxic action of chromium.     

Effect of chromium on the level of IL-12 and IFN-gamma in occupationally exposed workers

Chromium may affect humoral and cellular immunity, acting on T lymphocytes as well as on granulocytes and monocytes cells. Cytokines play an important role in the immune balance. In this study, the level of IL-12 and IFN-γ were evaluated in the sera and PHA/LPS stimulated culture supernatant of human PBMCs of healthy volunteers and occupationally exposed chromium workers. All the workers were highly exposed to chromium having mean of 104.65 ± 77.21 µg/dL (range 23.7-316.8 µg/dL). A suspension of exposed and unexposed human PBMC (0.5 × 10⁶ cells/ml) prepared and cultured in RPMI-1640 supplemented with 10% FCS for 18 h in the presence or absence of LPS (10 ng/ml) which used for stimulation of IL-12 and IFN-γ. The level of IL-12 and IFN-γ were evaluated in the sera samples as well as LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers. In these chromium exposed workers the level of IL-12 was 433.66 ± 197.49 pg/ml and 983.45 ± 330.99 pg/ml in LPS stimulated culture supernatant of normal individuals and highly chromium exposed workers, which was significant (P < 0.05). Although the level of IL-12 was (78.61 ± 61.03 pg/ml to 146.52 ± 46.37 pg/ml) elevated in unstimulated culture supernatant of h-PBMCs of chromium exposed individuals as compared to control, but it was not significant. This observation also suggests that a significant increase in IFN-γ production in LPS stimulated and unstimulated culture supernatant of h-PBMCs of chromium exposed workers as compared to control. However, IFN-γ level have a significant positive correlation between blood chromium level (r = 0.833, t = 6.3872, P 0.05) and exposure time (in years) (r = 0.8916, t = 8.3540, P 0.05) of the occupationally exposed workers.     

Antaxia-telangiectasia mutated gene polymorphisms and susceptibility to chromosomal damage among polycyclic aromatic hydrocarbons exposed workers

The aim was to explore the relationship between the ataxia-telangiectasia mutated (ATM) gene polymorphisms and susceptibility to cytokinesis-block micronucleus among workers exposed to polycyclic aromatic hydrocarbons (PAH). Blood and urine samples of 140 PAH-exposed workers and 66 non-PAH-exposed workers were collected. Seven tagging single nucleotide polymorphisms in ATM gene were selected by pariwise r² method and minor allele frequency cutoff of 0.05 from Chinese genotype data in HapMap project. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the polymorphisms of ATM rs600931, rs652311, rs227060, rs227292, rs624366, rs189037 and rs228589. The results showed that ATM rs600931 AG and AG+AA genotypes exhibited significantly higher cytokinesis-block micronucleus (CBMN) frequency (11.14 ± 6.91‰ and 10.57 ± 6.82‰) than did the GG genotype (7.66 ± 5.69‰, P = 0.015 and 0.038, respectively). The subjects with rs189037 GA and GA+AA genotypes exhibited significantly higher CBMN frequency (10.99 ± 6.90‰ and 10.51 ± 6.76‰) than that of the GG genotype (7.72 ± 5.82‰, P = 0.018 and 0.035, respectively). The PAH-exposed workers with rs624366 GC and GC+CC genotypes exhibited significantly higher CBMN frequency (11.34 ± 6.74‰ and 10.73 ± 6.62‰) than did the GG genotype (7.61 ± 6.07‰, P = 0.001 and 0.003, respectively). rs227092 GT genotype exhibited significantly higher CBMN frequency (10.78 ± 6.60‰) than did the GG genotype (7.91 ± 6.30‰, P = 0.025) among the PAH-exposed workers. The haplotype pairs GGGGTGC/AAACATT exhibited significantly higher CBMN frequency (12.05 ± 7.40‰) than did the GGGGTGC/GGGGTGC (7.51 ± 6.19‰, P = 0.007) among the PAH-exposed group. In conclusion, it is suggested that the polymorphisms of ATM were associated with the CBMN frequencies among PAH-exposed workers.     

Levels of antimony,arsenic, cadmium,copper, lead,mercury, selenium,silver, tin and zinc in bone tissue of industrially exposed workers

The contents of the elements antimony, arsenic, cadmium, copper, lead, mercury, selenium, silver, tin and zinc in bone tissue from autopsy specimens of the femur of workers who had been exposed to a large number of metals in a smeltery and refinery in Northern Sweden as well as of a control group have been quantitatively assayed.The analytical techniques used were atomic absorption spectrophotometry, neutron activation analysis and particle induced X-ray emission analysis (PIXE) in a proton microprobe. Increased levels of lead in the bone tissue of exposed workers compared to a non-exposed control group were observed. The median level of lead in the group of exposed workers exceeded the corresponding value of the control group about 5 times.Using the proton microprobe in the PIXE-mode, concentration profiles of copper, lead and zinc were examined within the Haversian system of the bone samples.     

Impairment of chemotaxis of polymorphonuclear leukocytes from lead acid battery workers

Since lead impairs in vitro the functions of macrophagic cells, we have studied the chemotactic activity of polymorphonuclear leukocytes (PMNs) obtained from lead acid battery workers who were removed from exposure one month before, because they had an abnormal lead absorption. Controls were 18 age matched subjects without any history of occupational lead exposure. Both lead acid battery workers and controls had no alterations of the blood haematological and metabolic parameters. Chemotaxis was carried on in Boyden chambers using zymosan activated serum as chemotactic stimulus. The chemotactic indexes are 56.4 +/- 8.7 in acid battery workers and 75.6 +/- in controls. The difference, which is statistically significant, shows that lead workers have an impairment of PMNs chemotactic activity.