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Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens.

OBJECTIVE: To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers. METHODS: Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl). RESULTS: Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use. CONCLUSION: In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

Adult↗

Calcium disodium ethylenediaminetetraacetate-chelated lead as a predictor for subclinical lead neurotoxicity: follow-up study on gun-metal foundry workers.

OBJECTIVES: To examine if chelated lead was a more predictive indicator of the subclinical effect of lead on conduction velocities of faster or slower nerve fibers as compared with blood lead (BPb). METHODS: Distribution of conduction velocities (DCV) in large myelinated fibers of the sensory median nerve was measured twice at a 1-year interval in 17 male gun-metal foundry workers with BPb concentrations of 22-59 (mean 40.2) microg/dl and a mobilization yield of lead into urine (MPb) by calcium disodium ethylenediaminetetraacetate of 0.15-2.09 (mean 1.19) mg/24 h for the 1st year and in 20 healthy males (controls). RESULTS: Yearly changes in the conduction velocities of faster fibers were significantly correlated with the corresponding change in MPb (P < 0.05) but not with that in BPb (P > 0.05). In ten workers showing an increase in MPb during the 1-year period (0.44 mg/24 h on average) the conduction velocities of faster fibers were decreased significantly, resulting in the values being significantly lower in all the workers combined than in the controls (P < 0.05). On the other hand, in the remaining workers, who showed a lesser extent of reduction in MPb (0.08 mg/24 h on average), the DCV did not change (P > 0.05). CONCLUSION: Chelated lead might be a more predictive indicator of the effect of lead on the conduction velocities of faster fibers than blood lead.

Adult↗

On the toxic effects of tetraethyl lead and its derivatives on the chrysophyte Poterioochromonas malhamensis. IV. Influence of lead antidotes and related agents.

The unicellular alga Poterioochromonas malhamensis was exposed to 12.5 microM of inorganic or triethyl lead and simultaneously treated with lead antidotes and related agents at concentrations of 12.5, 31.25 and 62.5 microM. With increasing concentrations some of the antidotes alone slightly to severely inhibited algal growth (BAL, CaNa2EDTA, EDTA, Na2EDTA), whereas others (DPA, EGTA, DIZO) were non-toxic at the concentrations tested. EGTA and CaNa2EDTA, at all concentrations tested, completely suppressed the growth inhibition caused by inorganic lead; Na2EDTA and EDTA were protective at the lower or medium concentrations, but DIZO, DPA and BAL considerably enhanced lead toxicity with increasing concentrations. None of the tested agents was able to reduce the toxic effects of triethyl lead. All antidotes markedly increased inhibition of algal growth caused by triethyl lead and some were even lethal to the poisoned algae either at the highest (Na2EDTA, EDTA, DPA) or at all concentrations used (DIZO, BAL). P. malhamensis proved to be a highly sensitive and valuable tests system and the results obtained exhibited striking parallels to medical and clinical experience in therapy of human poisoning with inorganic and organic lead compounds.

Antidotes↗

The contribution of drinking water lead to maternal blood lead concentrations.

The association between domestic water lead concentrations and blood lead concentrations has been examined in 232 mothers at delivery. The blood lead was found to vary significantly with the cube root of the water lead. This association was stronger for first flush water lead rather than for running water lead. This study emphasises the danger to mothers and to their children of environmental lead over-exposure in areas of soft acid plumbosolvent water.

Adolescent↗

Effect of plumbing systems on lead content of drinking water and contribution to lead body burden.

Stable lead isotopes and lead contents in drinking water from a number of Australian cities have been measured to determine the contribution of drinking water to body burden. Lead contents are generally < 2 micrograms/l and thus contribute an insignificant amount to the lead budget in humans in Australia. First-flush and running water samples taken at intervals of up to 10 min show that equilibrium is reached within 1 min or approximately 10 l by volume. There is, however, large variability in both lead content and isotopic composition within the first minute which brings into question the reliability of the recommended sampling time of 30 s. Extremely large isotopic differences between individual dwellings within the one city and between dwellings and the storage tanks for the water supply are attributed to differences in lead residing in the plumbing within the dwellings, usually from lead solder in brass fittings. Isotopic analysis of solder and water from two dwellings confirm this relationship.

Australia↗

Lead (II)-dithiothreitol equilibria and their potential influence on lead inhibition of 5-aminolevulinic acid dehydratase in in vitro assays.

Dithiothreitol (threo-2,3-dihydroxy-1,4-dithiobutane = DTT) has recently been used to activate 5-aminolevulinic acid dehydratase in kinetic studies for the inhibition of this zinc enzyme by lead. Since the DTT molecule contains donor groups capable of forming metal ion complexes, its presence in the experimental medium used for this kind of assay may largely influence the concentration of lead available for the active sites of the enzyme. Before any quantitative investigation of this phenomenon can be contemplated, all possible complexes formed by lead with DTT must first be identified and their stabilities determined. Accordingly, formation equilibria of DTT complexes with lead(II) have been investigated under physiological conditions (37 degrees C, NaCl, 0.15 mol. dm-3 using glass electrode potentiometry. Corresponding stability constants were refined with MINIQUAD and ESTA computer programs. DTT log protonation constants have been found equal to 9.811 +/- 0.002 and 18.672 +/- 0.002. The following lead-dithiothreitol complexes have been characterized: ML (12.243 +/- 0.063), MLH-1 (2.391 +/- 0.061), M2LH-1 (13.285 +/- 0.059), and M4L3 (51.668 +/- 0.157). Appropriate computer simulations show that the interactions of the two reactants are indeed most significant under the pH and concentration conditions used in the above mentioned biological investigations. In particular, the influence of lead(II)-DTT equilibria on the free concentration of lead available for the active sites of the enzyme is described.

Binding Sites↗

Dose response relationships during perinatal lead administration in the rat: a model for the study of lead effects on brain development.

Pregnant rats were dosed with 300, 600, 1000, 2000, 3000 or 4000 ppm inorganic lead through their drinking water during pregnancy and during lactation until 21 days post partum. An effect on live litter size was noted at the higher doses as was an increased tendency for sperm positive females to fail to produce a litter. Dose related responses were seen in the offspring for brain weight, body weight, body length and blood lead at birth and at age 21 days. In neonates from the dose groups above 1000 ppm Pb these 3 indices of growth indicated that there was an effect of lead on nutrition. The 300 ppm, 600 ppm and 1000 ppm dose groups showed no significant dose related effects for body length or brain weight and only slight effects on body weight. These low dose groups gave average blood lead values of 39.8 micrograms/100 ml blood, 54.6 micrograms/100 ml blood and 85.4 micrograms/100 ml blood respectively in the 21-day old neonates. These values correspond to blood lead values in children with so called "subclinical lead poisoning" and we suggest the use of this regime as a model to investigate effects of lead on development of the nervous system.

Animals↗

Effect of environmental temperature on tissue lead accumulation in mice repeatedly treated with lead acetate.

The effect of environmental temperature on lead accumulation in tissues of mice repeatedly treated with lead acetate (2 mg/kg per day and 5 mg/kg per day) for 3 or 6 weeks was studied. In blood, kidney and liver, the amount of lead accumulated after 3 weeks of treatment was markedly higher in animals exposed to 22 degrees C than those maintained at 35 degrees C. Conversely, when the treatment was extended to 6 weeks, lead concentrations in the liver and kidney were equal or higher respectively, in the mice exposed to 35 degrees C. In the brain, lead concentration was lower than that found in kidney and liver and it was independent of dose and ambient temperature of lead being higher at 35 degrees C than at 22 degrees C. These results demonstrate that environmental temperature influences the amount of lead accumulated in some rodent tissues, and that the duration of the treatment modifies the effect produced by temperature, suggesting that the changes elicited during the period of acclimation to the hot environment could be responsible for these findings.

Animals↗

Uptake and accumulation of lead by plants from the Bo Ngam lead mine area in Thailand.

A field survey of terrestrial plants growing on Bo Ngam lead mine area, Thailand, was conducted to identify species accumulating exceptionally high concentrations of lead. Plant and soil samples were collected from five areas. Lead concentrations in surface soil ranged from 325 to 142,400 mg/kg. The highest lead concentration in soil was found at the ore dressing plant area and lowest at a natural pond area. In different areas, the concentrations of lead in plants were different when comparing various study sites. A total of 48 plant species belonging to 14 families were collected from five sampling sites. Twenty-six plant species had lead concentrations more than 1000 mg/kg in their shoots. Three species (Microstegium ciliatum, Polygala umbonata, Spermacoce mauritiana) showed extremely high lead concentrations in their shoots (12,200-28,370 mg/kg) and roots (14,580-128,830 mg/kg).

Biodegradation, Environmental↗

Effectiveness of leaded petrol phase-out in Tianjin, China based on the aerosol lead concentration and isotope abundance ratio.

The phase-out of leaded petrol has been a measure widely used to reduce atmospheric lead pollution. Since the 1980s, China began to promote unleaded petrol. In order to assess the effectiveness of the measure an isotope fingerprint technique was applied for aerosol samples in the city of Tianjin. After dilute acid leaching, the lead concentration and isotope abundance ratios were determined for 123 samples collected in Tianjin during eight years (1994-2001). The 206Pb/207Pb ratio was lower in summer, when coal combustion emission was low and vehicle exhaust became more important, indicating that the 206Pb/207Pb ratio of leaded petrol in Tianjin is lower than that of aerosol samples. The 206Pb/207Pb ratio gradually increased from 1994 to 2001, a trend that suggests that the contribution from vehicle exhaust was diminishing. Overall, the measurements matched well with national statistical data of leaded and unleaded petrol production. After the nationwide switch to unleaded gasoline, comprehensive control measures are urgently needed to reduce air lead pollution in China, as aerosol lead reduced slightly but remains at a relatively high level.

Aerosols↗

Comparison of lead attenuation and lead hardening equivalence of materials used in respect of diagnostic X-ray shielding.

Present interest is in the shielding of diagnostic X-ray units. Numerical comparison has been made of the attenuation and hardening properties of lead and some particular alternative materials: steel, plate glass and gypsum wallboard. Results show, for particular choices of thickness, that lead and steel can be made to provide closely similar attenuation and spectral hardening, values of lead attenuation equivalent (LAE) and lead hardening equivalent (LHE) thicknesses being nearly the same. Significant differences in the attenuation and hardening properties of lead are found in comparison with plate glass and gypsum wallboard. LAE produces better matching of exposure for lead-plate glass and lead-gypsum wallboard than LHE.

Diagnostic Imaging↗

A comparison of X-ray fluorescence and wet chemical analysis for lead on air filters from different personal samplers used in a secondary lead smelter/solder manufacturer.

Portable X-ray fluorescence (XRF) technology may provide faster turn-around without compromising accuracy when assessing personal exposures to metals such as lead, but it has only been tested in limited field environments. This study is part of a series, where various types of sampler are used to collect airborne lead in different environments for presentation to a portable XRF analyzer. In this case personal samples were taken at a manufacturer of solder alloys consisting mainly of lead and tin, using the closed-face 37 mm cassette (CFC), the 37 mm GSP or "cone" sampler, the 25 mm Institute of Occupational Medicine (IOM) inhalable sampler, the 25 mm button sampler, and the open-face 25 mm cassette. Mixed cellulose-ester filters were used in all samplers. Following XRF analysis the samples were extracted with acid and analyzed by inductively coupled plasma optical emission spectroscopy (ICP). The internal surfaces of CFC's and 25 mm open-face cassettes were also wiped, and the wipes analyzed for lead to assess wall-losses in these two samplers. Analysis of all elements present is useful to ascertain contributions to matrix interference effects. In addition to lead, other metals such as tin, copper, iron, silver, cadmium and antimony were also detected in some or all of the samples by ICP analysis, but only copper and iron could be determined using the XRF analyzer under test. After the removal of a few outliers, all five samplers gave good correlations (r(2) > 0.9) between the two analytical methods over the entire range of found lead mass, which encompassed both the action level and the permissible exposure limit enforced in the USA by the Occupational Safety and Health Administration (OSHA). Linear regression on the results from most samplers gave almost 1 ratio 1 correlations without additional correction, indicating an absence of matrix effects, particularly from tin, which was the most common element after lead. The average of three XRF readings across filters from the GSP samplers gave the best results with 96.7% of results within +/-25% and 100% within +/-30% of the associated ICP values. Using the center reading only was almost as good with 90.0% of results within +/-25% and 96.7% within +/-30% of the associated ICP values, and results can be obtained faster with a single reading. The use of an algorithm developed by OSHA for three readings from the CFC filter samples gave the next best results with 93.3% of XRF results within +/-25% of the corresponding ICP values. However, analysis of wipes from the interior of the cassettes indicated a substantial loss of sample to the walls, and even larger wall-losses were encountered in the 25 mm open-face cassette. Neither this latter sampler nor the IOM or button sampler met the 95% criterion, even for +/-30% accuracy.

Air Pollutants, Occupational↗

The relationship between blood lead, bone lead and child intelligence.

We report associations between serial measures of blood lead and intelligence in children age 10-12 years, half heavily exposed to lead from the prenatal period onward, and half relatively unexposed. For a subsample, we examine bone lead-IQ associations, comparing them with bone lead associations. Both blood and bone lead levels were associated with intelligence decrements, small relative to the contribution of social factors. For each doubling of Tib-Pb, Full Scale, Performance, and Verbal IQ decreased by an estimated 5.5, 6.2, and 4.1 points, respectively. Bone lead-IQ associations were stronger than those for blood lead, which nonetheless provide robust analogues. Current BPb, easy to obtain, provides a useful means for assessing Pb exposure/IQ associations.

Bone and Bones↗

Lead in bone. IV. Distribution of lead in the human skeleton.

Flameless atomic absorption spectroscopy was used to measure lead concentrations in samples from 5 selected human skeletal sites (tibia, skull, rib, ilium, and vertebra) obtained from 134 hospital autopsies. Lead was distributed unequally among the different bones in distinct patterns that were age-, and to some extent, sex-dependent. To estimate lead concentration of the entire skeleton, all skeletal bones were divided into 5 groups based on their approximate compact/trabecular bone ratios, considering each of our 5 sampled sites to be the prototype for each such group. Regression analysis of the 10 possible bone site pair values at different ages yielded age-related constants. These constants were incorporated into an equation we developed that can be used both to estimate mean skeletal lead concentration (Pb) of the entire body skeleton and also to predict the lead concentration at any of the other 4 bone sites if any 1 of the 5 is measured. Applications of these data to in vivo bone lead measurements are detailed with respect to selection of the site to be measured, estimation of total skeletal lead burden, anticipated variations or error, and dependence of these factors on age and sex of the sampled population.

Adolescent↗

Lead bioavailability in the environment of children: blood lead levels in children can be elevated in a mining community.

Lower blood lead averages in mining communities, compared with other child exposure settings, e.g., innercity areas of the United States and smelter communities, have been attributed to lower bioavailability of lead to children in the mining areas. Direct supporting evidence of the lower bioavailability has, however, generally been lacking. Elevated blood lead levels for approximately 85% of children with > 10 micrograms/dl have been reported from the Broken Hill mining community in Australia. Lead isotope, optical, and scanning electron microscope analyses on the lead species from soils and dusts show them to be derived mainly from weathered ore body material. Solubility tests using 0.1M HCl on the -53 + 38 microns fraction of soil and dust show the lead species to have a high degree of bioavailability. Ingestion of soil and dust, either directly or via mouthing activity, is the main source and pathway for elevated blood lead in children from this community.

Australia↗

Cellular and molecular toxicology of lead. I. Effect of lead on cultured cell proliferation.

Growth studies were done on a cultured rat liver cell line (RLC-GAI) grown in a chemically defined medium in the presence of lead nitrate. Lead reversibly inhibited the growth of these cells even after 6 d of exposure to the heavy metal. To compare lead sensitivity in various cell lines, GI50 and LD50 values were determined in the RLC-GAI cells as well as two glioma cell lines (B82 and C(6)) and a neuroblastoma cell line (N18). The LD50 values paralleled but were consistently lower than the GI50 values. Since lead is known to affect heme synthesis, hemin was added to test the possibilty of preventing the growth-inhibitory effect of the lead. The growth capacity of lead-treated cells did not change with the addition of hemin. It is thought that differentiated cultured cell lines such as these could be useful in examining the molecular mechanism of lead toxicity.

Animals↗

Cellular and molecular toxicology of lead. II. Effect of lead on delta-aminolevulinic acid synthetase of cultured cells.

The effect of lead nitrate on delta-aminolevulinic acid synthetase (ALA synthetase), the first and rate-limiting enzyme of the heme biosynthetic pathway, was studied by using an established rat liver cell line (RLC-GAI). Lead was shown to produce a time-dependent increase in ALA synthetase activity, with a maximum after incubation of the cells for 24 h with 10(-5) M lead nitrate. The effect of lead was not liver-specific in that increases in enzyme activity were produced in other tissue-derived cell lines. Cycloheximide but not actinomycin D, cordycepin, or hydroxyurea, at concentrations that inhibit the synthesis of protein, RNA, and DNA, prevented the lead-associated increase in ALA synthetase activity. Heme, added to the cells as hemin, also prevented the effect of lead. These results indicate that lead induced the synthesis of ALA synthetase secondary to an inhibition of the synthesis of heme.

5-Aminolevulinate Synthetase↗

Cellular and molecular toxicology of lead. III Effect of lead on heme synthesis.

The effect of lead nitrate on the biosynthesis of heme and the cellular uptake of (59)Fe was studied in an established rat liver cell line (RLC-GAI) grown in serum-free medium. Heme synthesis was shown to be increased in lead-treated cells when determined by measuring the amount of (59)Fe incorporated into the heme fraction of cell homogenates; concomitant with increased (59)Fe incorporation into heme, cellular uptake of (59)Fe was also increased. By contrast, heme synthesis was inhibited by lead in a dose-dependent manner when determined by measuring the conversion of ((14)C) aminolevulinic acid into heme under identical experimental conditions. Cellular degradation of heme was not found to be significantly affected by lead. It is proposed that lead inhibited the biosynthesis of heme and that the increased incorporation of (59)Fe into the heme fraction of the lead-treated cells was the result of the increased uptake of (59)Fe and hence labeling of the heme molecules. Evidence is presented that suggests that only (59)Fe present in solution as a low-molecular-weight complex was accumulated in increased amounts by lead-treated cells.

Animals↗