Effects of Exposure to Lead on Selected Biochemical and Haematological Variables

Abstract: Blood and urine samples were taken from 34 persons occupationally exposed to lead and from 56 non-exposed control persons and blood lead and haemoglobin concentrations, red blood cell count, erythrocyte glutathione peroxidase (GSH-peroxidase) and acetylcholinesterase (AChE), and urinary δ-aminolevulinic acid were determined. Blood lead concentrations of the lead-exposed subjects were within the range generally accepted as safe for occupationally-exposed adults in many countries (i.e. below 50 μg Pb/dl blood). Yet, significant dose-dependent elevations were found in erythrocyte GSH-peroxidase and urinary δ-aminolevulinic acid. The urinary δ-aminolevulinic acid concentration of lead-exposed smokers was significantly elevated over that of lead-exposed non-smokers. Smoking did not affect the urinary δ-aminolevulinic acid concentration of control persons. In addition, a statistically significantly lower red blood cell count was observed in the lead-exposed group. Our results indicate that the above described safety standard for blood lead concentrations in occupationally exposed adults, although generally accepted, needs revision.     

In vitro effects of lead, mercury and cadmium on the enzymic activity of red-blood cell pyrimidine 5'-nucleotidase

The decrease of pyrimidine 5'-nucleotidase (P5N) in human erythrocytes, detected in persons occupationally exposed to lead (Pb), is not an in vitro artefact resulting from the release of lead during erythrocyte hemolysis but is a true reflection of the enzyme activity in vivo. Like Pb, mercury (Hg) and cadmium (Cd) ions exhibit an important in vitro inhibitory action on the P5N enzymic activity. However, when the metals are preincubated as metallothionein complexes with P5N preparations, their inhibitory power disappears.     

Determinants of inorganic arsenic methylation capability among residents of the Lanyang Basin,Taiwan: arsenic and selenium exposure and alcohol consumption

The objective of this study was to assess individual variation in inorganic arsenic methylation capability and the association between selenium levels in urine and blood, and inorganic arsenic methylation capability among residents of the Lanyang Basin who drank groundwater and were exposed to high concentrations of inorganic arsenic. According to the arsenic concentration of their drinking water, they were equally and randomly classified into four groups of 252 persons. It turned out that the higher the concentration of arsenic in well water was and thus the cumulative arsenic exposure, the higher the total inorganic arsenic metabolites in urine (total As(i)) and the overall inorganic and organic arsenic in urine (overall As(i+o)) were. The percentage of inorganic arsenic significantly decreased and the DMA percentage significantly increased as the concentration of urinary selenium and serum alpha-tocopherol increased. It appeared that urinary selenium levels increased the metabolism by methylation of arsenic, a finding that requires further investigation.     

Genetic variability in the system of natriuretic B peptide and principal toxicological parameters in workers exposed to lead

The study was aimed at evaluating the influence of selected polymorphisms of natriuretic peptide B precursor (NPPB) and natriuretic peptide receptor C (NPR3) genes on blood lead concentration (Pb-B) and blood zinc protoporphyrin concentration (ZnPP) in persons occupationally exposed to lead. Investigations were conducted on 360 persons (mean age: 44.49 ± 9.62 years), workers exposed to lead compounds. The analysis examined four polymorphisms of BNP gene, i.e.,: rs198388, rs198389, rs632793, and rs6676300; as well as one polymorphism of receptor C for natriuretic peptides, i.e., rs1421811. Heterozygosity in locus rs632793 of NPPB gene may result in higher concentrations of Pb-B, while allele A in locus rs632793 of NPPB gene seems to determine higher concentrations of ZnPP in persons occupationally exposed to lead. Workers exposed to lead and carrying allele C in locus rs198388 of NPPB gene, particularly in the heterozygotic setup, seem to be predisposed to present higher concentrations of ZnPP. Carriership of A allele in locus rs198389 of NPPB gene probably determines higher concentrations of ZnPP in study group. In summary, among persons occupationally exposed to lead, certain relationships were demonstrated between rs632793, rs198388 and rs198389 polymorphisms of NPPB gene and principal toxicological parameters characterizing exposure to lead.     

Concentrations of arsenic,cadmium and lead in human hair and typical foods in eleven Chinese cities

Concentrations of arsenic (As), cadmium (Cd) and lead (Pb) were determined in 384 human hair samples and 445 purchased food samples from 11 cities in China. The mean concentrations of hair As, Cd and Pb were 0.23, 0.062 and 2.45 mg kg⁻¹, respectively. The As, Cd and Pb concentrations in different foods were lower than the national maximum allowable contaminant levels. By comparison, males had higher hair As concentrations but lower Cd concentrations than females. When the interaction effects of gender and age were considered, males had the higher hair As, Cd and Pb concentrations in the 51–65 year-old age group. Residents of rural areas had higher hair As, Cd and Pb concentrations than people living in urban areas. Further analysis indicates that hair As, Cd and Pb concentrations and their changes with biological and environmental factors cannot be satisfactorily explained by the estimated intakes from purchased food.     

Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 ± 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I — men occupationally exposed to lead (n = 53), and group II — men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently in group I than in group II. In eTracking examination mean values of stiffness parameter (β), augmentation index (AI) and one-point pulse wave velocity (PWV-β) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness.     

Metal(loid) levels in biological matrices from human populations exposed to mining contamination--Panasqueira Mine (Portugal)

Mining activities may affect the health of miners and communities living near mining sites, and these health effects may persist even when the mine is abandoned. During mining processes various toxic wastes are produced and released into the surrounding environment, resulting in contamination of air, drinking water, rivers, plants, and soils. In a geochemical sampling campaign undertaken in the Panasqueira Mine area of central Portugal, an anomalous distribution of several metals and arsenic (As) was identified in various environmental media. Several potentially harmful elements, including As, cadmium (Cd), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), and selenium (Se), were quantified in blood, urine, hair, and nails (toe and finger) from a group of individuals living near the Panasqueira Mine who were environmentally and occupationally exposed. A group with similar demographic characteristics without known exposure to mining activities was also compared. Genotoxicity was evaluated by means of T-cell receptor (TCR) mutation assay, and percentages of different lymphocyte subsets were selected as immunotoxicity biomarkers. Inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis showed elevated levels of As, Cd, Cr, Mn, and Pb in all biological samples taken from populations living close to the mine compared to controls. Genotoxic and immunotoxic differences were also observed. The results provide evidence of an elevated potential risk to the health of populations, with environmental and occupational exposures resulting from mining activities. Further, the results emphasize the need to implement preventive measures, remediation, and rehabilitation plans for the region.     

Function of respiratory system evaluated using selected spirometry parameters in persons occupationally exposed to lead without evident health problems

This study aimed at evaluation of selected spirometric parameters in persons occupationally exposed to lead without evident health problems. The studies were conducted on 69 men occupationally exposed to lead. Occupational exposure to lead was characterized by estimation of blood lead concentration (Pb-B) and blood zinc protoporphyrin concentration (ZnPP). Function of respiratory system was examined using spirometric analysis with evaluation of its basic parameters: forced vital capacity (FVC), forced expiratory volume (in 1 s) (FEV1), Tiffeneau index (FEV1%VC) and peak expiratory flow (PEF). In the study group negative linear correlations were documented between Pb-B and FVC, FEV 1 and FEV1%VC. A more pronounced age, higher values of BMI and higher blood lead concentration constituted independent risk factors for reduced FEV1%VC.ConclusionPersons occupationally exposed to lead with elevated blood lead concentration and blood zinc protoporphyrin concentration manifested the impaired function of respiratory system, evaluated using parameters of spirometry.     

Assessment of cardiovascular risk in workers occupationally exposed to lead without clinical presentation of cardiac involvement

PURPOSE: The objective of this study was to assess, with aid of SCORE system, of 10-year risk of fatal cardiovascular incidents among workers occupationally exposed to lead, without circulatory system disorders. METHODS: The studies included 83 men (mean age: 55.14±4.62 years): the 1st group consisted of persons occupationally exposed to lead (group I, n=40), and 2nd group - persons not exposed to lead (group II, n=43). 10-Year risk of fatal cardiovascular incidents was assessed with application of SCORE risk chart designed for Polish population. RESULTS: In the first group, mean values of SCORE calculated on the basis of the chart including total cholesterol concentration in serum were significantly higher. Also, there were significantly higher: mean values of SCORE calculated on the basis of the chart including total cholesterol to HDL cholesterol ratio, mean values of relative SCORE, percentage of individuals with risk estimated as increased, percentage of individuals with risk estimated as significantly increased. Simultaneously, the significantly lower percentage of individuals with risk estimated as small or moderate was found in the occupationally exposed subjects. CONCLUSIONS: Persons occupationally exposed to lead compounds are burdened with significantly higher 10-year risk of fatal cardiovascular incident than individuals from the same population not exposed to lead.     

Prevalence and associated demographic characteristics of exposure to multiple metals and their species in human populations: The United States NHANES, 2007–2012

Lead (Pb), cadmium (Cd), mercury (Hg), and arsenic (As) are among the top 10 pollutants of global health concern. Studies have shown that exposures to these metals produce severe adverse effects. However, the mechanisms underlying these effects, particularly joint toxicities, are poorly understood in humans. The objective of this investigation was to identify and characterize prevalent combinations of these metals and their species in the U.S. NHANES population to provide background data for future studies of potential metal interactions. Exposure was defined as urine or blood levels ≥ medians of the NHANES 2007–2012 participants ≥6 years (n = 7408). Adjusted-odds ratios (adj-OR) and 95% confidence intervals were determined for covariates (age, gender, and race/ethnicity, cotinine and body mass index). Species-specific analysis was also conducted for As and Hg including iAs (urinary arsenous acid and/or arsenic acid), met-iAs (urinary monomethylarsonic acid and/or dimethylarsinic acid), and oHg (blood methyl-mercury and/or ethyl-mercury). For combinations of As and Hg species, age- and gender-specific prevalence was determined among NHANES 2011–2012 participants (n = 2342). Data showed that approximately 49.3% of the population contained a combination of three or more metals. The most prevalent unique specific combinations were Pb/Cd/Hg/As, Pb/Cd/Hg, and Pb/Cd. Age was consistently associated with these combinations: adj-ORs ranged from 10.9 (Pb/Cd) to 11.2 (Pb/Cd/Hg/As). Race/ethnicity was significant for Pb/Cd/Hg/As. Among women of reproductive age, frequency of oHg/iAs/met-iAS and oHg/met-iAs was 22.9 and 40.3%, respectively. These findings may help prioritize efforts to assess joint toxicities and their impact on public health.     

Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats

Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures.     

Placental concentrations of mercury,lead, cadmium,and arsenic and the risk of neural tube defects in a Chinese population

To examine whether in utero exposure to mercury (Hg), cadmium (Cd), lead (Pb) and arsenic (As) is associated with an elevated neural tube defects (NTDs) risk, placental concentrations of total Hg, Cd, Pb and As were measured with an inductively coupled plasma mass spectrometer (ICP-MS) in 36 anencephaly and 44 spina bifida cases as well as in 50 healthy controls. The median Hg concentration in the NTD cases (2.25 ng/g) was higher than that of the controls (1.16 ng/g). The odds ratio (OR) for an Hg concentration above the median was 8.80 (95% CI 3.80–20.36) for the NTD cases. NTD risks increased for the second and third high levels of the concentrations, with ORs of 2.70 (95% CI 1.13–6.43) and 18.20 (95% CI 5.45–60.73), respectively. Therefore, higher placental levels of Hg are associated with an elevated risk of NTDs.     

The concentration of protoporphyrin IX in workers occupationally exposed to lead

In the study a relationship was undertaken between the concentration of erythrocyte protoporphyrin IX and concentrations of lead and hemoglobin in blood as well as iron serum concentration in men workers exposed to lead. The test group were 54 men, 28-56 years of age, occupationally exposed to lead for a period of 9-33 years. The control were 40 men not exposed to lead, between 25-60 years of age. The test group was divided into 3 subgroups according to exposure duration. As regards the concentrations of protoporphyrin and other parameters examined, the study revealed no significant differences between the subgroups. Those concentrations were also found to be similar in respective control groups. Significantly increased level of protoporphyrin IX concentration was noted in 17 men out of the whole test group. However as compared with other groups results, all the remaining parameters showed no difference. As regards the concentrations of iron in serum and hemoglobin in blood, they fell within the range of physiological values, in all the groups studied.     

In vitro and in vivo effect of mercury, lead and cadmium on the generation of chemiluminescence by human whole blood

A method based on the use of the luminogenic substance, luminol, was developed for measuring the respiratory burst induced by phorbolmyristate acetate in 4 microliters of human whole blood. In vitro, the three cations, Hg2+, Pb2+ and Cd2+, inhibit the peak luminescence response at concentrations higher than those usually found in blood of subjects exposed to these metals. Cadmium metallothionein, however, in a concentration range similar to that found in whole blood of workers exposed to cadmium strikingly reduces the respiratory oxidative burst. In workers exposed to inorganic lead or mercury vapour, no reduction of the chemiluminescence response of whole blood was observed while a slight but statistically significant reduction was found in whole blood from cadmium exposed workers. If a similar effect occurs in lung macrophages, it might decrease the respiratory tract resistance to infection.     

Evaluation of lead exposure in battery‐manufacturing workers with focus on different biomarkers

The influence of exposure to lead on the frequency of micronuclei (MN), nuclear buds and nucleoplasmatic bridges was investigated in peripheral blood lymphocytes in 15 male battery‐manufacturing workers and 15 controls matched for age and smoking habits. In addition to MN test, blood lead (B‐Pb) and cadmium (B‐Cd), delta aminolevulinic acid dehydratase (ALAD) activity, erythrocyte protoporphyrin (EP), serum vitamin B₁₂ (S‐Vit B₁₂) and folate (S‐folate) were determined in all subjects. Lead‐exposed subjects had significantly higher MN frequency and B‐Pb concentrations than controls. In control smokers we found a significant negative correlation between B‐Pb concentration and frequency of nucleoplasmatic bridges, and nuclear division index. In control non‐smokers a significant positive correlation was observed only between age and nuclear buds frequency, and between S‐folate and B‐Pb level. In lead exposed smokers, significant positive correlations between MN frequency and S‐Vit B₁₂, S‐folate, and nuclear buds frequency were found. A positive correlation in exposed smokers was also found between nuclear buds frequency and S‐Vit B₁₂ concentration. A negative correlation was found between ALAD and EP, and B‐Pb in exposed smokers. Exposed non‐smokers showed significant negative correlation between MN frequency and B‐Cd, and ALAD and EP. The results indicate a genotoxicity of lead, pointing to a micronucleus assay as a relevant test for assessing genotoxic effects resulting from occupational exposure. The other indicators did not necessarily follow the results of THE MN test. Influence of smoking should be further investigated. Copyright © 2009 John Wiley & Sons, Ltd.     

Estimation of the dietary intake of cadmium, lead, mercury, and arsenic by the population of Santiago (Chile) using a Total Diet Study.

Dietary intake of arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) by the population of Santiago (Chile) was determined using a Total Diet Study in the market basket modality. After conducting a survey of the foods consumed in the last 24 h, the most consumed food products were included in the basket. Subsequently, they were cooked or prepared according to typical Chilean procedures and grouped into 17 food categories according to their chemical characteristics. The fish and shellfish group had the highest contents of As (1351 ng/g wet weight, ww), Cd (277 ng/g ww), and Hg (48 ng/g ww), while the sugar group had the highest content of Pb (251 ng/g ww). For a person with a body weight of 68 kg, the dietary intakes of As (77 microg/day), Cd (20 microg/day), Hg (5 microg/day), and Pb (206 microg/day) are lower than the provisional tolerable weekly intake values established by the FAO/WHO. Consequently, the total intakes of As, Cd, Hg, and Pb in Santiago (Chile) are within the limits estimated as safe.     

Simultaneous determination of heavy metal pollution in commercial traditional Chinese medicines in China

A rapid and accurate method of quantifying heavy metal pollution in commercial traditional Chinese medicines (TCMs) is described. The method uses modified wet digestion for sample preparation and atomic absorption spectrophotometry for detecting the content of copper (Cu), cadmium (Cd), arsenic (As), lead (Pb) and mercury (Hg). The determination limits of the method were 0.001, 0.002, 0.001, 0.001 and 0.001 mg/kg for Cu, Cd, As, Pb and Hg, respectively. The method was applied to the quantification of heavy metal pollution in 50 different commercial TCMs in a total of 250 samples. Heavy metal contents in the samples investigated were found at different levels. The level of As did not exceed the legal limit stated in the China pharmacopoeia 2010, whereas Cu, Cd, Pb and Hg were above permitted levels in some samples.     

Correlation between environmental low-dose cadmium exposure and early kidney damage: A comparative study in an industrial zone vs. a living quarter in Shanghai,China

To investigate heavy metal exposure in an industrial zone vs. a living quarter in Shanghai and explore the relationship between the heavy metal source and urine cadmium (Cd) and early kidney damage. Blood lead and urine Cd, manganese (Mn), mercury (Hg), arsenic (As) and EKD indexes were compared between residents in Exposure group (n = 168) and Control group (n = 168). It was found that PM_2.5 level in Exposure group was significantly higher than that in Control group, and serum Cys-C and urine Cd, NAG, mAlb, KIM-1 and Cd-MT levels in Exposure group were also significantly higher than those in Control group, suggesting that differences in urine Cd and heavy metal levels between the residents of the two groups may be due to different PM_2.5 concentrations in the environments of the two areas. Cd accumulation within the human body can induce kidney damage, probably through its potential hazard to the proximal tubular epithelial cells.     

Heavy metals exposure is associated with early liver dysfunction among rural residents aged 40–75 years in southwest China

Heavy metals exposure has been associated with liver dysfunction in recent reports, while the hepatoxicity of lead (Pb) and cadmium (Cd) has been well established. However, the combined effects of multi-metal in real-world scenario on liver dysfunction are still unclear. This cross-sectional study examined associations between 10 biomarkers of early liver injury and multiple heavy metals levels. The levels of heavy metals/metalloid (magnesium [Mg], calcium [Ca], iron [Fe], zinc [Zn], arsenic [As], Cd, copper [Cu], and Pb) were measured in blood and urinary sample collected from 725 participants in a Cd-polluted area and an unpolluted area in southwest China. The early liver dysfunction biomarkers included the liver enzymes (ALT, ALP, AST, and GGT), proteins (TP, ALB, and GLO), and bilirubin (TBIL, DBIL, and IBIL). Confounder-adjusted beta coefficients were determined using multiple linear regression model analysis for the group-classified and gender-classified samples. Our results showed that blood Fe, Cd, and Cu levels were found to be positively related to elevated ALT levels and blood Cu was positively associated with AST levels in the Cd-polluted area, while the highest blood Zn quartile in the polluted area and blood Mg quartile in the unpolluted area were associated with lower ALT levels. Our finding implies that industrial pollution results in heavy metals of Cd and Pb exposure and effects of Fe, Cd, Cu, and Pb in the Cd-polluted area may be the main contributors to increase the risk of liver dysfunction while Zn in the Cd-polluted area and Mg in the unpolluted area may be the protective factors.     

Bovine blood quality control material for cadmium, mercury, and lead

A protocol is elaborated for the preparation and characterization of a quality control material (QCM) containing intrinsic concentration of cadmium (Cd) (0.8 microgram/L) and lead (Pb) (13.4 micrograms/dL) from bovine blood and an elevated QCM containing Cd (5.0 micrograms/L), mercury (Hg) (11.2 micrograms/L), and Pb (34.5 micrograms/dL) from bovine blood spiked with aqueous spiking-solutions prepared with salts of Cd, Hg, and Pb. Borosilicate glass septum vials of 7-mL capacity were filled with 5 mL of blood, sealed with Teflon-silicone discs and plastic screw caps, and stored at -20 degrees C. Quality control, intervial and intravial, and storage stability values for Cd, Hg, and Pb were ascertained by analyzing the blood in randomly selected vials by an internal laboratory using modified published methods which were established for detection limit, accuracy, and precision. Validation of the protocol was demonstrated by intravial and intervial homogenity for Cd, Hg, and Pb and no change occurred in the concentrations of the elements in bovine blood containing EDTA at storage temperatures of 4 degrees C and -20 degrees C for 2 years.