Abstract  1 Dietary lead intakes, blood lead concentrations and water lead concentrations were measured and their relationships investigated for 31 adults and 11 infants living in dwellings in Ayr with lead plumbing. 2 For adults, some lead intakes were found to be higher than the provisional tolerable weekly intake for lead, and for infants most of the intakes were high. 3 A cube root relationship fitted the data on blood lead versus water lead better than a linear relationship. Similarly, blood lead varied with the cube root of weekly dietary lead intake. 4 These cube root equations provided a means of estimating the impact on blood lead concentrations of exposure to lead from food and water. If cube root relationships correctly describe the association between these parameters, then the curve fitted to the results for adults indicates that the contribution to the blood lead concentrations from sources other than the diet and water was relatively small.

Abstract  The first year of data for 10 pm particles from the Environmental Protection Agency's Inhalable Particulate Network are summarized and discussed. The discussion includes comparison among the various samplers and particulate size fractions. The data base is composed of measurements made on an every-sixth-day sampling schedule at eight different locations in 1982. This preliminary review indicates that the overall ratio of the 10 Ám fraction (PM10) to Total Suspended Particulate (TSP) is 0.485 and the relationship is reasonably linear. The relationships between PM10 and the 15 Ám fraction (IP) are very linear for all sites, increasing the utility of the existing Inhalable Particulate data bases.

Abstract  The results of this study confirm that low lead (0.01%) but not high lead (0.5%) administration results in increased blood pressure in rats treated for up to 12 months. This effect appeared to be related to an imbalance of endothelially-derived vasoconstrictor and vasodilator compounds in low lead-treated animals but not in high lead-treated animals. In low lead-treated rats, measurement of plasma endothelins 1 and 3 (ET-1 and ET-3) revealed that ET-3 concentration increased significantly after both 3 months (Experimental, 92.1 +/- 9.7 v Control, 46.7 +/- 12.0 pmol/mL; P < .001) and 12 months (Experimental, 105.0 +/- 9.3 v Control, 94.1 +/- 5.0 pmol/mL; P < .01) while ET-1 was unaffected. Plasma and urinary cGMP concentrations (as a reflection of endothelium-derived relaxing factor (EDRF)) decreased significantly at 3 months (plasma, Experimental, 1.8 +/- 0.9 v Control, 4.2 +/- 1.6 pmol/mL; P < .001) and 12 months (plasma, Experimental, 2.2 +/- 0.7 v Control, 4.2 +/- 0.9 pmol/mL; P < .001). Thus, the path to development of hypertension in low lead rats may be through an increase in the concentration of the vasoconstrictor hormone, ET-3, and a decrease in the vasodilator hormone, EDRF. High levels of lead exposure did not result in hypertension, perhaps because plasma concentrations of ET-1, ET-3 and cGMP were unaltered at 3 months, while ET-1, ET-3 and cGMP concentrations were coordinately and significantly decreased at 12 months.

Abstract  Potential reversibility of the reproductive effect of lead was studied in female albino rats after cessation of oral exposure to 7500 ppm lead as acetate in drinking water. Females mated and gave birth to their first offspring during 9 weeks of lead exposure. They then continued or discontinued exposure, were mated for the second time, and had their second offspring during a longer exposure (20 weeks) or after a period without lead. Food consumption, body weights, and fertility index were not altered irrespective of the exposure conditions. In the first and especially in the second offspring of exposed females, survival rates, litter sizes, and body weights of newborn and 11-day-old pups were decreased. Offspring born to dams in which exposure had been stopped were not different from controls. It was concluded that the adverse reproductive action of lead is reversible after withdrawal of the female from exposure.

Abstract  Background Chronic lead exposure causes hypertension and cardiovascular disease, which are associated with, and, in part, due to oxidative stress. While occurrence of oxidative stress in lead-exposed animals and cultured endothelial cells has been well-established, direct and specific evidence on the type of the reactive oxygen species (ROS) produced by lead-exposed vascular cells is lacking and was investigated. Methods Human coronary endothelial (EC) and vascular smooth muscle cells (VSMC) were incubated in appropriate culture media in the presence of either 1 ppm or 10 ppm lead acetate or sodium acetate (control) for 1 to 30 minutes or 60 hours. Productions of superoxide and hydrogen peroxide in the cell populations were determined by flow cytometry using hydroethidine and dihydrorhodamine, respectively. Data from a minimum of 10,000 cells were collected and analyzed using Cell Quest software. In addition, Cu Zn superoxide dismutase (SOD), catalase, glutathione peroxidase (GPX), and NAD(P)H oxidase (gp91phox) were measured. Results Short-term lead exposure resulted in a significant rise in both superoxide and hydrogen peroxide production by both EC and VSMC. After long-term exposure, detectable superoxide levels fell to near normal level, while hydrogen peroxide production remained high. This was associated with up-regulations of gp91phox, elevation of superoxide dismutase, reduction of VSMC catalase, and no change in GPX levels. Together, these events can account for the observed decline in superoxide and the rise in hydrogen peroxide following long-term lead exposure. Conclusion Lead exposure promotes generation of superoxide and hydrogen peroxide in human EC and VSMC. This phenomenon can potentially contribute to the pathogenesis of the lead-associated hypertension and cardiovascular disease, and points to the potential benefit of lowering lead burden in the exposed populations.

Abstract  Lead exposure is considered to be a risk factor of cardiovascular disease. To investigate the relationship between lead and cardiovascular disease/hypertension in lead exposure, beta-adrenergic system is explored in this study. We address three topics in this study: (a) the relationship between beta-adrenergic receptor and lead level in heart, aorta, and kidney of lead-exposed rats; (b) the relationship between beta-adrenergic receptor in heart, aorta, kidney, and blood pressure in lead-exposed rats; and (c) the change of cyclic AMP level in heart, aorta, and kidney of rats with different lead levels. Wistar rats were chronically fed with 2, 1, 0.5, 0.1, 0.05, and 0.01% lead acetate and water for 2 months. Plasma catecholamine level was measured by high-performance liquid chromatography. Radioligand binding assay was measured by a method that fulfilled strict criteria of beta-adrenoceptor using the ligand [125I]iodocyanopindolol. Cyclic AMP (cAMP) level was determined by radioimmunoassay. The levels of lead were determined by electrothermal atomic absorption spectrometry. The results showed that increased plasma norepinephrine level, decreased aorta beta-adrenergic receptor and cAMP, and increased kidney beta-adrenergic receptor and cAMP contributed to the elevation of blood pressure in lead-induced hypertension. The decrement of beta-adrenoceptor and cAMP in heart resulted in decreased contractility in heart.

Abstract  Kinetic and metabolic balance studies in a healthy man fed a diet normal in lead content and labeled with lead-204 indicated that approximately two-thirds of his assimilated lead was dietary in origin; the remainder was inhaled. Kinetic analysis shows that the isotopic data can be interpreted by a three-compartment model.

Abstract  Lead is a toxic and carcinogenic metal that has been extensively associated with male reproductive abnormalities. The purpose of this study was to establish the effects of lead on the primate seminal vesicle. Sixteen cynomolgus monkeys maintained in environmentally controlled conditions were orally administered gelatin capsules containing 1500 micrograms lead acetate/kg bw/day. Monkeys were randomly assigned to the following groups: control (n = 3) which received 95% glycerol and 5% distilled water (vehicle) over their lifetime, infancy (limited to the first 400 days of life; n = 4), post-infancy (dosed following 300 days of life to 9 years of age; n = 5) and lifetime exposure (9 years; n = 4). At necropsy, the seminal vesicles from each animal were removed, fixed in glutaraldehyde, and processed for ultrastructural analysis by conventional methods. The glands from animals in the control group consisted of acini lined by two cell types, viz., tall columnar secretory cells, and round basal cells. Secretory cells possessed microvilli, basally located nuclei surrounded by much rough endoplasmic reticulum, a few lipid droplets, and supra-nuclear regions dominated by pleomorphic membrane-limited secretory granules. All the treated groups exhibited an augmentation in the number of lipid droplets within the secretory cells. In both the infancy and post-infancy groups, a marked reduction in electron-dense cores of the secretory droplets was observed in severely affected regions of the glands. These findings support the evidence that lead is a potent reproductive toxicant, however, further research is needed to determine the consequences of this damage on reproductive performance.

Abstract  Studies were performed to investigate the effects of chronic, low level pre- and post-natal lead exposure on cell-mediated immune function in rats. Weanling female rats were exposed to lead (as lead acetate) in their drinking water at 0, 25, and 50 ppm for 7 weeks. At the end of 7 weeks they were mated with untreated males and continued on the same dosage throughout gestation and lactation. The offspring of these females were weaned at 21 days of age and continued on the same lead exposure regimen as their mothers. These offspring were used in immune surveillance procedures between 35 and 45 days of age. Lead exposure at the levels employed had no statistically significant effect on growth and did not result in overt signs of toxicity. Thymic weights were significantly decreased in both males and females of the two lead dosage groups. Furthermore, lead exposure resulted in suppression of responsiveness of lymphocytes to mitogen stimulation and in reduced delayed hypersensitivity responsiveness. Results indicate that chronic low-level lead exposure causes suppression of cell-mediated immune function.

Abstract  Lead-containing organic compounds such as tetraethyl and tetramethyl lead have been used for over 50 years as anti-knock additives to petrol. The occupational hazards associated with their production and use are well documented, but no adverse effects of environmental pollution by organolead compounds have yet been demonstrated. Here we present an analysis of 22 human brains which shows that a significant part of the lead content may be organolead. The highest concentrations (median, 2 times 10-7 mol per kg) were present in individuals residing in the lower floors of buildings in the city.

Abstract  Lead intoxication of mice increased the mortality due to experimental Langat virus infection. Lead enhanced viral replication, resulting in early detection and higher virus multiplication in the brain with associated widespread and more severe neurohistological changes. More severe brain damage by the virus in lead intoxicated mice contributed to increased mortality since Langat virus is known to kill by its encephalitogenic potential.

Abstract  Male and female rats whose mothers had been exposed to Pb before and during pregnancy and lactation at exposure levels of 0, 0.5, 5, 25, 50, and 250 ppm Pb as Pb-acetate in drinking water were continued on the respective regimens for 6 or 9 months. Body weights of males and females were not significantly different from controls at 6 months of age; however, female body weights were significantly decreased at 250 ppm at 9 months of age. In males at 9 months of age, spleen weights were significantly increased at 250 ppm Pb and kidney weights were increased at 0.5 ppm Pb and above; in females the liver, pituitary, and heart weights were affected at 250 ppm Pb. No significant Pb effects were found in sperm counts or sperm morphology, hematology profiles, or serum chemistries. Blood, brain, femur, and kidney Pb levels as well as urinary ALA excretion were all significantly dose related. Histopathological lesions were noted in the spleen (250 ppm) and in the kidney as evidenced by cytomegaly/karyomegaly (beginning at 5 ppm in males; 25 ppm in females), nuclear inclusion body formation and increased numbers of iron-positive granules within renal proximal tubule cells. These effects were more marked after 9 months exposure. Ultrastructural studies revealed mitochondrial swelling and the presence of increased numbers of lysosomes within renal proximal tubule cells. Energy-dispersive X-ray microanalysis, performed on adjacent sections, showed the highest intracellular Pb concentrations in nuclear inclusion bodies within renal proximal tubule cells. Inhibition of renal mitochondrial respiration for both succinate and NAD-linked substrates was found in 50- and 250-ppm Pb exposure groups at 9 months but not at 6 months. Mitochondrial ?-aminolevulinic acid synthetase and ferrochelatase, but not ?-aminolevulinic dehydratase, were also found to be inhibited at these Pb levels at 9 months. The lowest exposure level resulting in a detectable effect of Pb (cytomegaly/karyomegaly in renal proximal tubule cells) was 5 ppm associated with a median blood Pb concentration of 11 ug/dl.

Abstract  #Background- Lead and cadmium exposure may promote atherosclerosis, although the cardiovascular effects of chronic low-dose exposure are largely unknown. The objective of the present study was to evaluate the association between blood levels of lead and cadmium and peripheral arterial disease. Methods and Results- We analyzed data from 2125 participants who were 40 years of age in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES). Peripheral arterial disease was defined as an ankle brachial index <0.9 in at least 1 leg. Lead and cadmium levels were measured by atomic absorption spectrometry. After adjustment for demographic and cardiovascular risk factors, the ORs of peripheral arterial disease comparing quartiles 2 to 4 of lead with the lowest quartile were 1.63 (95% CI, 0.51 to 5.15), 1.92 (95% CI, 0.62 to 9.47), and 2.88 (95% CI, 0.87 to 9.47), respectively (P for trend=0.02). The corresponding ORs for cadmium were 1.07 (95% CI, 0.44 to 2.60), 1.30 (95% CI, 0.69 to 2.44), and 2.82 (95% CI, 1.36 to 5.85), respectively (P for trend=0.01). The OR of peripheral arterial disease for current smokers compared with never smokers was 4.13. Adjustment for lead reduced this OR to 3.38, and adjustment for cadmium reduced it to 1.84. Conclusions- Blood lead and cadmium, at levels well below current safety standards, were associated with an increased prevalence of peripheral arterial disease in the general US population. Cadmium may partially mediate the effect of smoking on peripheral arterial disease.

Abstract  The effects of elevated blood lead on semen quality were evaluated in the rabbit model and compared to published effects in humans. Mature, male rabbits were given lead acetate by subcutaneous injection in the dose range of 0 to 3.85 mg/kg on a Monday-Wednesday-Friday basis. In each of eight treatment groups, a dosing regimen was developed to produce blood lead levels of 0, 20, 40, 50, 70, 80, 90, and 110 μg/dL. A 5-week pre-exposure period was followed by a 15-week exposure testing period allowing for response through six cycles of the seminiferous epithelium. Semen analyses revealed that increased blood lead levels were associated with adverse changes in the sperm count, ejaculate volume, percent motile sperm, swimming velocities, and morphology. Hormonal responses were minimal. Testicular pathology revealed a dose-dependent inhibition of spermiation. For six measures of semen quality, threshold estimates ranged from 16 to 24 μg/dL. Using the species extrapolation factor derived in this study, a rabbit dose would have to be divided by 1.56 to obtain the equivalent human dose for an equal percentage decrease in sperm concentration; however, rabbits are 3.75 more sensitive in terms of absolute decrease in sperm count for a given blood lead level.

Abstract  House lead exposure is generally assessed using total lead, except in France, where acid-leachable lead is used for routine regulatory purposes. In order to allow an international comparison of French lead dust contamination, a sequential digestion protocol is developed to determine both leachable and total lead on the same sample with a two-step digestion stage: firstly, hydrochloric acid is added to the sample at 37°C to solubilize leachable lead; then nitric acid is added to an aliquot at 95°C to solubilize residual (i.e., non-leachable) lead. Both sample fractions are analyzed with inductively coupled plasma mass spectrometry (ICP-MS). The sum of the two fractions allows to determine total lead. This new protocol has been tested with wiped dust (n = 111) and paint chip (n = 46) samples collected in houses (n = 16). The leachability of lead ranged from 63 to 100% in dust and from 4 to 100% in paint. These findings confirm the strong variability of lead leachability in houses samples and thus the importance of considering it for lead poisoning prevention. This double determination of leachable and total lead for each wiped dust or paint sample appears to be a reproducible, simple, low-cost protocol and thus a useful tool for international comparison of house dust lead contamination.

Abstract  Solid solutions of calcium hydroxyapatite (CaOHA) and lead hydroxyapatite (PbOHA) of the formula Ca10−x Pbx (PO4)6 (OH)2 were prepared by coprecipitation followed by heating at 800°C in a stream of CO2-free water vapor of 1 atm. The samples were apatitic in the range 0

Abstract  The crystal structures of Pb2+ ion-exchanged hydroxyapatite (OHAp), chlorapatite (ClAp), and fluorapatite (FAp) in aqueous solutions with low pH value of 3.0 or 4.0 have been investigated by X-ray powder pattern-fitting methods. The site occupancy factors of Pb atoms for the M1 (column site) and M2 sites were determined to be 0.72 and 0.77 for Pb7.5Ca2.5---OHAp, 0.69 and 0.86 for Pb7.9Ca2.1---ClAp, and 0.60 and 0.52 for Pb5.5Ca4.5---FAp, respectively. These results imply that Ca2+ ions in calcium hydroxyapatite are exchanged for Pb2+ ions in acidic aqueous solution regardless of whether they occupy M1 or M2 sites.

Abstract  Heavy metal contamination from occupational origin is a cause for concern because of its potential accumulation in the environment and in living organisms leading to long term toxic effects. This study was aimed to assess Cd, Cr, Mn, Ni and Pb levels in whole blood, urine, axillary hair and saliva from 178 individuals with occupational exposure to heavy metals. Levels of metal compounds were determined by atomic absorption spectrometry. We collected information on occupation, lifestyle habits and food intake by questionnaire. Multiple linear regression analyses for metal ion concentration in whole blood, urine, axillary hair and saliva were adjusted for age, gender, smoking and alcohol consumption, lifetime workplace exposure, residence area and food habits. Overall, blood and urine median concentrations found for the five metals analyzed do not exceed biological exposure indexes, so that they are very similar to a non-occupationally exposed population. Toxicokinetic differences may account for the lack of correlations found for metal levels in hair and saliva with those in blood or urine. For those heavy metals showing higher median levels in blood with respect to hair (Cd, Mn and Pb) indicating lesser hair incorporation from blood, the lifetime working experience was inversely correlated with their hair levels. The longer the lifetime working experience in industrial environments, the higher the Mn and Ni concentration in saliva. Axillary hair and saliva may be used as additional and/or alternative samples to blood or urine for biomonitoring hair Mn, and saliva Ni in subjects with occupational exposure.

Abstract  Lead mortality analyses by quintiles and 3 strata for Pb Integrated Science Assessment.

Abstract  Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death, and its prevalence is increasing; however, few strategies are available for disease prevention or modification besides smoking interventions. To facilitate examination of modifiable risk factors for COPD in the Nurses' Health Study, the authors validated a questionnaire-based definition of COPD in a subset of this US cohort. Participants were surveyed biennially about lifestyle factors, including smoking, since 1976 and physician diagnosis of COPD since 1988. Self-reported cases were defined as reporting COPD on both the original (1988-1996) and supplemental (1998) questionnaires. The authors requested medical records for a 10% random sample of 2,790 cases and reviewed these records in a systematic, blinded fashion. Validated cases required obstructive spirometry, emphysema on chest radiograph or computed tomography, or physician diagnosis. COPD was confirmed for 78% of 273 cases. Spirometry or radiographic results were available for 84%; when available, mean forced expiratory volume in 1 second was 51% predicted (standard deviation, 19). Applying these results to a hypothetical cohort, the authors estimated the degree to which disease misclassification biases relative risks toward the null value, confirming that questionnaire-based COPD research should focus on minimizing false positives rather than false negatives. In conclusion, COPD can be studied in large, questionnaire-based cohorts of health professionals.

Abstract  Lead has been shown to exert toxic effects during early development. In these in vivo and ex vivo experiments, the effect of lead on the immune system of the developing embryo was assessed. Nine-week-old female Fischer 344 rats were exposed to lead acetate (0, 100, 250, and 500 ppm lead) in their drinking water during breeding and pregnancy (exposure was discontinued at parturition). Offspring received no additional lead treatment after birth. Immune function was assessed in female offspring at 13 weeks of age. Dams in lead-exposed groups were not different from controls with respect to the immune endpoints used in these experiments; however, in the offspring, lead modulated important immune parameters at modest exposure levels. Macrophage cytokine and effector function properties (tumor necrosis factor-alpha and nitric oxide production) were elevated in the 250 ppm group, while cell-mediated immune function was depressed, as shown by a decrease in delayed-type hypersensitivity reactions in the 250 ppm group. Interferon-gamma levels were decreased in the 500 ppm treatment group. Serum levels of IgE were increased in rats exposed to 100 ppm lead. These results indicate that exposure of mothers to moderate levels of lead produces chronic immune modulation in their F344 rat offspring exposed in utero. Since the mothers were not susceptible to chronic immune alterations, a developmental bias to the immunotoxic effects of lead is indicated. The differences observed are consistent with the possibility that lead may bias T helper subset development and/or function, resulting in alterations in the balance among type 1 and type 2 immune responses.

Abstract  Parameters of semen quality, seminal plasma indicators of secretory function of the prostate-and seminal vesicles, sex hormones in serum, and biomarkers of lead, cadmium, copper, zinc, and selenium body burden were measured in 240 Croatian men 19-52 years of age. The subjects had no occupational exposure to metals and no known other reasons suspected of influencing male reproductive function or metal metabolism. After adjusting for age, smoking, alcohol, blood cadmium, and serum copper, zinc, and selenium by multiple regression, significant (P<0.05) associations of blood lead (BPb), delta-aminolevulinic acid dehydratase (ALAD), and/or erythrocyte protoporphyrin (EP) with reproductive parameters indicated a lead-related increase in immature sperm concentration, in percentages of pathologic sperm, wide sperm, round sperm, and short sperm, in serum levels of testosterone and estradiol, and a decrease in seminal plasma zinc and in serum prolactin. These reproductive effects were observed at low-level lead exposure (BPb median 49 mu g/L, range 11-149 mu g/L in the 240 subjects) common for general populations worldwide. The observed significant synergistic effect of BPb and blood cadmium on increasing serum testosterone, and additive effect of a decrease in serum selenium on increasing serum testosterone, may have implications on the initiation and development of prostate cancer because testosterone augments the progress of prostate cancer in its early stages.

Abstract  In this study, the size distribution of airborne particles and related heavy metals Co, Cd, Sn, Cu, Ni, Cr, Pb and V in two urban areas in Istanbul: Yenibosna and Goztepe, were examined. The different inhalable particles were collected by using a cascade impactor in eight size fractions (<0.4 μm, 0.4-0.7 μm, 1.1-2.1 μm, 2.1-3.3 μm, 3.3-4.7 μm, 4.7-5.8 μm, 5.8-9 μm and >9 μm) for six months at each station. Samples were collected on glass fiber filters and filters were extracted and analyzed using ICP-MS. Log-normal distributions showed that the particles collected at the Yenibosna site have a smaller size compared to the Goztepe samples and the size distribution of PM was represented the best by the tri-modal. The average total particle concentrations and standard deviations were obtained as 67.7 ± 17.0 μg m(-3) and 82.1 ± 21.2 μg m(-3), at the Yenibosna and Göztepe sites, respectively. The higher metal rate in fine and medium coarse PM showed that the anthropogenic sources were the most significant pollutant source. Principal component analysis identified five components for PM namely traffic, road dust, coal and fuel oil combustion, and industrial.