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Lead poisoning: II. Biological standards for occupational lead exposure--where do we stand now?

Lead poisoning is an occupational and environmental disease of great public health concern. During the past two decades major efforts have been made in many countries to minimize exposure to lead both in the occupational and general environment. Blood lead concentrations at which adverse effects can be detected have become progressively lower. Despite legislation concerning medical surveillance of lead-exposed workers and improvement in environmental control measures that took place during the 1980s, review of recent surveillance data indicates that excessive lead absorption among workers is still a problem in Israel. An approach is suggested for the reporting of surveillance data that will provide safety managers with the information necessary for introducing effective environmental control measures.

Adult↗

Lead toxicity part II: the role of free radical damage and the use of antioxidants in the pathology and treatment of lead toxicity.

Lead is an environmentally persistent toxin that causes neurological, hematological, gastrointestinal, reproductive, circulatory, and immunological pathologies. The propensity for lead to catalyze oxidative reactions and generate reactive oxygen species has been demonstrated in multiple studies. These reactive oxygen species (ROS) inhibit the production of sulfhydryl antioxidants, inhibit enzyme reactions impairing heme production, cause inflammation in vascular endothelial cells, damage nucleic acids and inhibit DNA repair, and initiate lipid peroxidation in cellular membranes. These wide-ranging effects of ROS generation have been postulated to be major contributors to lead-exposure related disease. Antioxidants - vitamins B6, C and E, zinc, taurine, N-acetylcysteine, and alpha-lipoic acid, either alone or in conjunction with standard pharmaceutical chelating agents - have been studied in lead-exposed animals. The evidence for their use in lead exposure, alone and in conjunction with chelating agents, is reviewed in this article.

Animals↗

Regional distribution of lead in the brains of lead-intoxicated adult mice.

The susceptibility of adult neural tissues to the detrimental effects of Pb poisoning has prompted the present distributional analysis of lead in the brains of chronically lead-exposed mice. A high-resolution microPIXE method was developed for measuring Pb in whole-brain cryosections derived from chronically lead-exposed mice. Spatial resolutions as small as 20 micron were obtained. Details of the methodology are presented together with procedures for Pb standard preparation and control measures employed to reduce potential errors of Pb assay associated with taking brain sections with steel alloy knives. The unique advantages of making microPIXE Pb determinations in nonpreselected brain anatomic regions using freeze-dried semithick cryosections are reviewed. The study revealed that, in lead-intoxicated mice, there existed wide regional variation in Pb concentration in the ppm range, in 50 micron sagittal or coronal sections. Higher Pb levels were found in discrete brain regions of lead-treated adult mice than in matched control brains. Suggestions for further studies of Pb kinetics using microPIXE methods in adults and immature animals, including components of neural barrier tissues, are reviewed.

Animals↗

Industrial lead exposure: a review of blood lead levels in South Island industries, 1974-83.

Relative risks of increased lead absorption found in 31 occupations were investigated. Serial red cell lead measurements on 1319 males and 186 females provided a mean and range for each occupational type. The magnitude of the mean and percentage of raised levels identified the degree of occupational risk. The mean red cell lead for 50% of employees was within the regional usual range for those not occupationally exposed. In 77% the mean red cell lead was less than 4.1 mumol/l. Of the remainder, 4% had levels greater than 5.7 mumol/l and 1% had levels greater than 7.7 mumol/l. Our findings have been used to manage local chronic and acute lead problems.

Erythrocytes↗

Influence of trimethyl lead and inorganic lead on the in vitro assembly of microtubules from mammalian brain.

The influence of trimethyl lead (TriML) and inorganic lead (Pb) on the in vitro assembly of microtubules (MTs) from tubulin of porcine brain was studied using turbidity measurements and electron microscopy. At concentrations of 150 to 650 microM Pb, no significant effects on the in vitro assembly of MTs could be detected by both methods. On the other hand, TriML increasingly blocked MT assembly at 100 to 200 microM and completely inhibited assembly at 300 microM TriML and higher concentrations. Application of 400 microM TriML to preassembled MTs caused an immediate drop of the optical density. Electron microscopy showed that one minute after addition of TriML to assembled MTs only very few intact MTs could be detected whereas ten minutes later MTs were completely absent. The observed increase of optical density following the TriML-induced drop was found to be due to the formation of clusters of aggregates but not to assembly of MTs. The results demonstrate that inorganic lead and trimethyl lead have different effects on the in vitro assembly of MTs. It is assumed that the selective neurotoxic effects of organic lead might be due, at least in part, to impairments of neurotubular structures and functions.

Animals↗

[Lead in the blood and protoporphyrin levels in erythrocytes in glass workers exposed to lead].

This paper investigates how the indicators of lead exposure (blood lead-PbB, delta-aminolevulinic acid dehydratase-delta-ALAD, erythrocyte protoporphyrin-EP), relate to the exposure duration prior to the analyses, alcohol intake, gamma-glutamyltranspherase (GGT), and smoking habits of 25 glass workers exposed to lead oxide over a period between 1988 and 1994. The PbB was analyzed with the ET ASS method, (ALAD with Standardized European Method) while EP with the spectrofluorometric method. The alcohol intake assessment was based on answers to a medical questionnaire. The results are presented as median values and analyzed by the method of Spearman Correlation. The findings show correlation between EP and the exposure duration to the lead dust over a period of three months prior to the analyses (r = +0.42; t = 2.2; p < 0.05). The median value of PbB was higher (2.4 mumol/L) in workers who consumed over 50 g of alcohol a day than in workers with lower alcohol consumption (1.9 mumol/L). The median value of PbB was higher in workers whose serum GGT surpassed the normal value of 0.66 mukat/L and was lower in workers with GGT lower than 0.66 mukat/L, (2.4 mumol/L and 2.05 mumol/L, respectively). ALAD was lower in the subgroup of workers with GGT higher than 0.66 mukat/L. The smokers manifested a higher median PbB value. The PbB values correlated with the alcohol intake and smoking habit, while the EP values correlated with the duration of exposure to lead dust.

Adult↗

Auditory event-related potential (P300) in relation to peripheral nerve conduction in workers exposed to lead, zinc, and copper: effects of lead on cognitive function and central nervous system.

By measuring auditory event-related potential (P300 and N100) and peripheral nerve conduction velocities, the subclinical effects of lead, zinc, and copper on the central and peripheral nervous system were examined in 22 male gun metal foundry workers exposed to these metals. Their blood lead (BPb) concentrations ranged from 12 to 59 micrograms/dl (median 30). Control subjects were 14 healthy workers, employed at the same factory, who had never been occupationally exposed to these metals. In the gun metal foundry workers, the latencies of P300 and N100 were significantly prolonged; the latency of P300 was significantly correlated with BPb concentrations and other indicators of lead absorption. Similarly, the maximal motor and sensory conduction velocities in the radial and median nerves were significantly slowed, and were significantly correlated with indicators of lead absorption. The data suggest that lead exposure at low levels affects cognitive and central auditory nervous system function together with peripheral nerve conduction.

Adult↗

Lead exposure in a tank demolition crew: implications for the new OSHA construction lead standard.

The Federal Occupational Safety and Health Administration (OSHA) has recently extended the basic health and safety provisions of the OSHA lead standard for general industry to workers in the construction industry. In this report we describe a tank demolition worksite that midway through the project strengthened its lead exposure control activities to a level that approximated the current lead standard. Of 12 tested ironworkers and laborers who worked at the site before the change, zinc protoporphyrin levels increased and seven developed blood lead levels (BLL) > 50 micrograms/dL. After the change these workers' BLLs declined. Six workers hired after the change did not experience increases in zinc protoporphyrin and none developed BLL > 25 micrograms/dL. The experience at this worksite demonstrates the usefulness and feasibility of implementing the current lead standard in construction settings.

Adult↗

Blood lead concentrations in marine mammals validate estimates of 10(2)- to 10(3)-fold increase in human blood lead concentrations.

Measurements of ultra-low ambient blood lead (PbB) concentrations (mean +/- SD = 0.13 +/- 0.06 micrograms/dL) in Northern elephant seal (Mirounga angustirostris) validate previous estimates of ultra-low PbB levels in preindustrial humans. These estimates had been unsubstantiated, since PbB levels in this range had never been measured in any organisms prior to this study. Similarities in PbB levels among these contemporary and preindustrial mammals are consistent with similarities in their measured and estimated lead exposures, respectively. The marginally higher PbB levels and rates of lead exposure in contemporary marine mammals are, also, consistent with lead isotopic composition analyses that indicate their PbB levels have been elevated from exposure to industrial lead. Consequently, these analyses substantiate concerns that current baseline PbB levels in humans, which are estimated to be two to three orders of magnitude above natural levels, may still constitute public health risks.

Animals↗

Measurement of the flux of lead from bone to blood in a nonhuman primate (Macaca fascicularis) by sequential administration of stable lead isotopes.

To better understand the kinetics of the transfer of lead from bone to blood, we have developed and tested a method in which sequential doses of lead, each enriched with a different stable isotope, were administered in a nonhuman primate Macaca fascicularis whose skeleton had been previously labeled with lead of known isotopic composition. Lead isotopic ratios of blood and bone samples, analyzed by thermal ionization mass spectrometry (TIMS), were unmixed by isotope dilution techniques. The first label administered allows the contribution from historical bone stores to be measured. Subsequent labels allow measurement of both the historical bone stores and the previous labels that have become recently incorporated into bone. The method may be extended to studies of bone lead mobilization in pregnancy, lactation, menopause, or in disease states such as postmenopausal osteoporosis.

Animals↗

The effects of CaEDTA injection on lead, zinc, copper and ALAD in erythrocyte, plasma and urine in lead-exposed workers: a 24-h observation.

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 micrograms/dl (mean 49 micrograms/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.

Adult↗

A rapid lead test: public outreach and testing to detect leachable lead in ceramic ware.

A modification of the U.S. Food and Drug Administration (FDA) lead screening test of ceramic ware was made to screen large numbers of samples in a short time frame. Ceramic ware in use by Davis and Sacramento, California residents was tested. Lead was leached from ceramic ware with citric acid and identified by rhodizonic acid in this quick, qualitative test. Of 92 individual pieces of pottery tested, approximately 6.6% were positive for leachable lead. Approximately 67% of the positive samples were handmade in Mexico. This rapid test is sensitive to two (2) parts per million (ppm, microgram/g) leachable lead. Ceramic ware with detectable leachable lead levels may present a health risk to individuals who habitually use such items for food storage and/or consumption. Because only 20-30 minutes is needed to perform the test, immediate communication of results to the participant is possible.

Ceramics↗

The effect of lead on protein and DNA metabolism of normal and lead-adapted rat kidney cells in culture.

Cultures of epithelial rat kidney cells were used to investigate the effect of lead on protein and DNA metabolism. Lead-adapted cells were cultured in 5 and 10 microM Pb(NO3)2 for several months and subsequently showed the same growth characteristics but a higher resistance to increased lead doses than untreated cells. Both normal and adapted cell types were exposed to lead nitrate in concentrations from 5 to 1000 microM for incubation periods of from 1 to 24 h. 3H-leucine incorporation was increased in 10 microM lead by up to 140% in normal but not in adapted cells, pointing to a resistance forming mechanism. Not only is the overall rate of protein synthesis increased, but separations of cytosolic proteins by SDS-polyacrylamide electrophoresis indicate the novel or increased synthesis of several proteins. A difference could also be observed in the DNA metabolism, where normal cells show a very pronounced increase of up to 900% after 24 h of incubation. This was not observed in adapted cells.

Adaptation, Physiological↗

Human lung cell growth is not stimulated by lead ions after lead chromate-induced genotoxicity.

Chromate compounds are known human lung carcinogens. Water solubility is an important factor in the carcinogenicity of these compounds with the most potent carcinogenic compounds being water-insoluble or 'particulate'. Previously we have shown that particulate chromates dissolve extracellularly releasing chromium (Cr) and lead (Pb) ions and only the Cr ions induce genotoxicity. Pb ions have been considered to have epigenetic effects and it is thought that these may enhance the carcinogenic activity of lead chromate, perhaps by stimulating Cr-damaged cells to divide. However, this possibility has not been directly tested. Accordingly, we investigated the ability of Pb ions to stimulate human lung cells and possibly force lead chromate-damaged cells to grow. We found that at concentrations of lead chromate that induced damage, human lung cells exhibited cell cycle arrest and growth inhibition that were very similar to those observed for sodium chromate. Moreover, we found that soluble Pb ions were not growth stimulatory to human lung cells and in fact induced progressive mitotic arrest. These data indicate that lead chromate-generated Cr ions cause growth inhibition and cell cycle arrest and that Pb does not induce epigenetic effects that stimulate chromate-damaged cells to grow.

Cations, Divalent↗

Effects of lead inclusion bodies on subcellular distribution of lead in rat kidney: the relationship to mitochondrial function.

The effect of Pb pretreatment on the subcellular binding of a tracer dose of 203Pb was studied in kidneys of rats in which intranuclear and cytoplasmic inclusion bodies had been induced by a single ip injection of Pb acetate (50 mg Pb/kg) 6 days earlier. Results of subcellular fractionation studies in rats injected iv with 203Pb 24 hr prior to sacrifice demonstrated that 203Pb activity was about 1.5 times higher in kidney homogenates and mitochondrial fractions of control compared to Pb-pretreated rats. Cytosolic 203Pb activity in control rats was 5 times higher than that in Pb-pretreated rats. In contrast, Pb pretreatment increased the 203Pb binding capacity to the nuclear and inclusion body fractions by 7 and 20 times, respectively, compared with controls. Pb pretreatment decreased total mitochondrial 203Pb binding but resulted in a higher proportion of 203Pb bound to the inner membrane and matrix fractions relative to the controls. After in vitro incubation of control renal mitochondria with 203Pb the binding to inner and outer membranes and matrix fractions increased with increasing concentration of unlabeled lead added to the incubation. Deposits on the inner membrane of isolated mitochondria from Pb-pretreated rats were observed by isotonic ammonium molybdate negative staining and these mitochondria also showed decreased respiratory control ratios (RCRs). Succinate-mediated respiration rates and membrane binding of the fluorescent probe ethidium bromide were not affected by Pb pretreatment. These data indicate that lead influences its own subcellular distribution in the kidney following Pb pretreatment as shown by the increase of nuclear and inclusion body binding and increase of mitochondrial inner membrane and matrix binding of lead. The mitochondrial inner membrane shows a preferential affinity for lead following in vivo treatment which can be correlated with impairment of a specific inner membrane function (depressed RCRs). Lead exposure did not alter the activity of the mitochondrial membranes to undergo energy linked conformational changes.

Animals↗

Lead and cadmium in fruiting bodies of macrofungi in the vicinity of a lead smelter.

The concentrations of lead and cadmium in the fruiting bodies of mycorrhizal and edible macrofungi (Basidiomycetes, Agaricales) were measured in the vicinity of a lead smelter. Very high concentrations of both metals were found 1 km from the stack, and elevated concentrations were observed up to a distance of 4.5 km. The dependence of the concentrations on the distance from the stack were approximated by an exponential function, the extrapolation of which showed that only at a distance of 6 km did the concentrations approach those reported from an area in the Krusné Hory Mountains with a medium level of air pollution. The concentrations of lead were slightly higher in the caps than in the stems of the fungal fruiting bodies from the sites close to the smelters; at a distance of 1.7 km they were the same, and at greater distances the lead concentrations in the caps were slightly lower than those in the stems. The cap/stem concentration ratio for cadmium does not exhibit any change with distance. The different behaviour of the two metals can be explained in terms of the lower mobility of Pb2+ ions. Because of their lead and cadmium contents, edible mycorrhizal fungi picked within a distance of 0.6 km of the stack can be toxic to man if eaten often in quantities that are usual in Czechoslovakia.

Agaricales↗

Exposure to lead and cadmium of children living near a lead smelter at Lavrion, Greece.

Exposure of children of the Greek town of Lavrion to lead and cadmium has been evaluated by determination of the levels of lead (PbB) and cadmium (CdB) in the blood of 514 children living in the town. The Lavrion area is heavily polluted by lead owing to the presence of a large lead-zinc mining and smelting industrial complex. The industrial PbB level (geometric mean) was 21.7 micrograms dl-1 (range 7.4-79.8 micrograms dl-1). The CdB levels were, on average, 0.36 micrograms l-1 (range 0.1-3.1 micrograms l-1). The results were evaluated with respect to a number of constitutional, social and environmental variables, such as age, gender, distance of the school from the lead-zinc mining and smelting complex, and occupation and education of the father.

Age Factors↗

The developmental consequences of low to moderate prenatal and postnatal lead exposure: intellectual attainment in the Cincinnati Lead Study Cohort following school entry.

In a further follow-up study of the Cincinnati Lead Study Cohort, 253 children were administered the Wechsler Intelligence Scale for Children-Revised (WISC-R) at approximately 6.5 years of age. Postnatal blood lead concentrations were inversely associated with Full-Scale (FSIQ) and Performance IQ (PIQ). Following statistical adjustment for developmental co-factors such as maternal IQ and an assessment of the quality of caretaking in the home environment, a statistically significant relationship remained between postnatal blood lead concentrations and PIQ. Further statistical analyses suggested that averaged lifetime blood lead concentrations in excess of 20 micrograms/dL were associated with deficits in PIQ on the order of approximately 7 points when compared to children with mean concentrations less or equal to 10 micrograms/dL. These results are discussed in terms of their consistency with other similar studies as well as their internal consistency with earlier reports on this cohort. The findings of this investigation support recent initiatives in the United States to reduce the exposure of children to environmental lead.

Child↗