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Development of an integrated microanalytical system for analysis of lead in saliva and linkage to a physiologically based pharmacokinetic model describing lead saliva secretion.

There is a need to develop reliable portable analytical systems for biomonitoring lead (Pb) in noninvasively collected saliva samples. In addition, appropriate pharmacokinetic analyses are used to quantitate systemic dosimetry based on the saliva Pb concentrations. A portable microfluidics/electrochemical device was developed for the rapid analysis of Pb based on square wave anodic stripping voltammetry, in which a saliva sample flows over an electrode surface, Pb2+ is chemically reduced and accumulated, and the electric potential of the electrode scanned. The system demonstrates a good linear response over a broad Pb concentration range (1-2000 ppb). To evaluate the relationship between saliva and blood Pb, rats were treated with single oral doses ranging from 20 to 500 mg Pb/kg of body weight, and 24 hours later were administered pilocarpine, a muscarinic agonist to induce salivation. To correlate saliva levels with internal dose, blood and saliva were collected and quantitated for Pb by inductively coupled plasma-mass spectrometry (ICP-MS) and by the microanalytical system. The quantitation with the microanalytical system was slightly less (approximately 75-85%) than with ICP-MS; however, the response was linear, with concentration suggesting that it can be used for the quantitation of salivary Pb. To facilitate modeling, a physiologically based pharmacokinetic (PBPK) model for Pb was modified to incorporate a salivary gland compartment. The model was capable of predicting blood and saliva Pb concentration based on a limited data set. These results are encouraging, suggesting that once fully developed the microanalytical system coupled with PBPK modeling can be used as important tools for real-time biomonitoring of Pb for both occupational and environmental exposures.

Animals↗

Experimental analysis of lead-in-air sources in lead-acid battery manufacture.

Plant-scale experimental sampling programs were carried out to determine the contribution to the lead-in-air exposure from (a) fork-truck transport of pasted plates in racks and (b) manual loading and unloading of plates from racks. Fork-truck transport was found not significant under "clean" conditions. Manual loading and unloading was found significant.

Air Pollutants, Occupational↗

Effect of lead ingestion on concentrations of lead in tissues and eggs of laying Tsaiya ducks in Taiwan.

This experiment was conducted to investigate Pb concentrations in soft tissues and eggs from laying Tsaiya ducks (Anas platyrhynchos var. domestica), dosed via gelatin capsule with 10 or 20 mg Pb/kg BW daily for 3 mo. Body weights of ducks were not influenced by Pb treatment. In addition, no clinical syndromes involving Pb intoxication were found throughout the experiment. The two levels of Pb consistently resulted in increases in the Pb content of blood, kidney, liver, and gizzard, whereas only 20 mg Pb/kg BW per d of dose additionally increased the Pb in femoral muscle. More Pb was deposited in the kidney and liver after Pb exposure than in the gizzard or femoral muscle. Lead residues in yolk and eggshell from Pb-dosed ducks were significantly higher than in controls; however, Pb in albumen was generally low and was not influenced by Pb treatment.

Administration, Oral↗

Derivation of a target level of lead in soil at residential sites corresponding to a de minimis contribution to blood lead concentration.

Inability to define either a clear toxicologic threshold or a stochastic all-or-nothing (cancer-type) response model for the noncarcinogenic effects of lead (Pb) in young children has posed difficulties for derivation of risk-based target levels of Pb in residential soil. Approaches based on empirical relationships between Pb levels in blood (PbB) and Pb in soil suffer from inability to specify the numerous variables which mediate between these two quantities. Approaches based on achieving a toxicologically de minimis target PbB level (e.g., 10 micrograms/dl) are subject to large uncertainty in estimating the distribution of existing PbB levels in a specific exposed population and in estimating the relative contribution from nonsoil sources of Pb. The multisource contribution to the distribution of PbB makes this approach unsuited for determination of a target Pb level in a single medium. An alternative approach is presented based on achieving a de minimis contribution to PbB (delta PbB) from soil. Contributions to Pb exposure from outdoor soil and indoor soil-derived dust (ISDD) are modeled and appropriate values are suggested for input parameters. This analysis predicts that chronic exposure of young children to 200 micrograms Pb/g (ppm) in residential soil will result in a delta PbB of 2 micrograms Pb/dl blood. This concentration of Pb in soil may provide an appropriate target level for residential soil when other significant sources of Pb exposure are present. In other cases, this approach can be used to predict a soil concentration of Pb corresponding to an appropriate non-de minimis delta PbB.

Absorption↗

Lead in petrol and levels of lead in blood: scientific evidence and social policy.

Two aspects of the recent controversy about the health consequences of lead in petrol are considered. Firstly, the evidence is shown to be deficient, largely because the basic epidemiological principles of representative sampling, realistic measurement, and control of confounding variables were not followed so that valid conclusions cannot be drawn from most of the published studies. Secondly, the role of science appeared to be comprised by confusion between science per se and social policy. Relations between the two are explored, and it is concluded that confusing them reduces the contribution that science can make to effective social policy.

Gasoline↗

Influence of bacterial strains isolated from lead-polluted soil and their interactions with arbuscular mycorrhizae on the growth of Trifolium pratense L. under lead toxicity.

We isolated two bacterial strains from an experimentally lead (Pb)-polluted soil in Hungary, 10 years after soil contamination. These strains represented the two most abundant cultivable bacterial groups in such soil, and we tested their influence on Trifolium pratense L. growth and on the functioning of native mycorrhizal fungi under Pb toxicity in a second Pb-spiked soil. Our results showed that bacterial strain A enhanced plant growth, nitrogen and phosphorus accumulations, nodule formation, and mycorrhizal infection, demonstrating its plant-growth-promoting activity. In addition, strain A decreased the amount of Pb absorbed by plants, when expressed on a root weight basis, because of increased root biomass due to the production of indoleacetic acid. The positive effect of strain A was not only evident after a single inoculation but also in dual inoculation with arbuscular mycorrhizal fungi. Strain A also exhibited higher tolerance than strain B when cultivated under increasing Pb levels in the spiked soil. Molecular identification unambiguously placed strain A within the genus Brevibacillus. We showed that it is important to select the most tolerant and efficient bacterial strain for co-inoculation with arbuscular mycorrhizal fungi to promote effective symbiosis and thus stimulate plant growth under adverse environmental conditions, such as heavy-metal contamination.

Bacillaceae↗

Roles of lead-binding proteins in mediating lead bioavailability.

The intracellular bioavailability of lead (Pb) at low dosage levels in major target organs such as the kidney and brain appears to be largely determined by complexation with a group of low molecular weight proteins. These proteins are rich in aspartic and glutamic dicarboxyl amino acids. The proteins are chemically similar but not identical across all species examined to date and the brain protein appears to be different from that found in the kidney. These proteins possess dissociation constant values for Pb on the order of 10(-8) M and appear to normally bind zinc. In rats, these proteins attenuate the Pb inhibition of the heme pathway enzyme delta-aminolevulinic acid dehydratase by a mechanism involving both Pb chelation and zinc donation to this highly Pb-sensitive zinc-dependent enzyme. Other studies in rats have shown that the kidney protein facilitates the intranuclear movement of Pb in vitro followed by chromatin binding, suggesting that this protein may be involved in alterations of the pathognomonic Pb intranuclear inclusion bodies in renal gene expression associated with the mitogenic effects of Pb in the kidney.

Animals↗

Severe lead poisoning from an imported clothing accessory: "watch" out for lead.

CASE REPORT: A case of severe lead poisoning following ingestion of an imported clothing accessory is reported. The child presented with abdominal pain, vomiting, and anemia but did not develop encephalopathy. RESULTS: Prompt removal of the object in conjunction with whole bowel irrigation and chelation therapy led to a favorable outcome.

Child, Preschool↗

[Morphological changes in the nervous system in lead poisoning. I. Experimentally induced lead neuropathy].

A morphological study on experimental model of lead (Pb) neuropathy (by the method of Pentschev, A., 1966) was described. Dense inclusions in Schwann's cells and satellite cells of the sensory ganglia were found by an electron microscope in the examined peripheral nerves (n. ischiadicus) and sensory ganglia (g. lumbale and g. trigeminale--Gasseri). These finding supported direct toxic action of Pb on these structures and proved their participation in the pathogenesis of developing neuropathy.

Animals↗

Lead concentration in Hong Kong roadside dust after reduction of lead level in petrol.

Samples of roadside dust were collected from 30 sites in Hong Kong. The total concentrations of 10 metals in the samples were analyzed, and the correlation coefficients among the metal contents and the annual average daily traffic (AADT) in 1986 were determined. Pb was found to have a significant correlation (P less than 0.01) with AADT. No correlation was found between Al, Ba, Cd, Cr, Cu, Fe, Mn, Ni, and Zn with respect to AADT. A general decrease in the level of Pb in roadside dust in the past few years has been observed since the reduction in the level of lead in petrol.

Dust↗

[Changes in blood lead, urinary alanine and coproporphyrins in workers exposed to high concentrations of environmental lead].

A study was conducted on a total of 200 workers whose duties bring them into contact with lead, to determine levels of total alanuria, plumbemia and coproporphyrins in urine, basophil spotting and Burton's fringe. It was noted that in all cases these levels exceeded the maximum permitted environmental concentration. 80% (?) presented high figures for alanuria and 84% had very high plumbaemia levels. Coproporphyrins were also high in more than 60% and also in more than 60% of cases, basophil spotting was found. On the other hand, Burton's fringe was only detected in a few. Lastly, an important fact which emerged was the high rate of absenteeism among this group of workers.

Alanine↗

Correlations between blood lead concentrations and some blood protein levels in children residing in lead-polluted and control areas.

Ninety children residing in a highly Pb-polluted area near a lead foundry (group E), and 61 children from the control area (group C) were examined and compared. In group E children there were detected significantly increased blood Pb concentrations (girls: 31.6 +/- 16 microgram/100 ml; boys: 38.7 +/- 15.8 microgram/100 ml) in comparison with the control group C children (about 20 microgram/100 ml for both sexes). Regression analysis revealed significantly positive correlation of Pb concentrations in blood with the level of total blood proteins and ALAD, the correlation with A-1AT, alpha-2-M, TRF, and CPL was much less pronounced. Also the correlation of Ca2+ concentrations in blood with blood protein levels was not too marked. On the other hand, the age factor turned out to be very influencing in girls. Remarkable was the change of Pb and Ca correlation positivity in group C children to correlation negativity in group E (ALAD, total proteins, CPL), or of correlation negativity to correlation positivity (A-1AT, TRF). The observed changes are discussed from the aspect of multifactorial action of Pb in the organism.

Adolescent↗

[Morphological changes in the nervous system in lead poisoning. II. Experimental lead-induced encephalopathy].

The morphological investigation in an experimental model of lead (Pb) encephalopathy (according to the method of A. Pentschew, 1966) is presented. Electron microscopy-dense inclusions are found out in the nuclei and cytoplasm of astrocytes and in some ependyma cells in the investigated cortical and subcortical (paraventricular) structure of the brain and spinal cord. This confirms the direct toxic action of Pb on these structures and proves their participation in pathogeneses of the developing encephalopathy. The established inclusions in the ependyma and the data about a disturbance of the blood-brain barrier give a reason to be proposed the possibility for a penetration of Pb in the nervous system not only through a blood but also through a cerebrospinal fluid way.

Animals↗

Lead activation of protein kinase C from rat brain. Determination of free calcium, lead, and zinc by 19F NMR.

Lead (Pb2+) has been reported to activate calcium/phospholipid-dependent protein kinase C (PKC) at subnanomolar concentrations (Markovac, J., and Goldstein, G. W. (1988) Nature 334, 732-734); however, others have failed to find any Pb(2+)-induced activation of PKC (Murakami, K., Feng, G., and Chen, S. G. (1993) J. Pharmacol. Exp. Ther. 264, 757-761). In neither of these studies was the actual free Pb2+ or Ca2+ concentration measured. In this study, 1,2-bis(2-amino-5-fluorophenoxy)ethane N,N,N',N'-tetraacetic acid (5F-BAPTA) was used to buffer Pb2+ and Ca2+ concentrations in the PKC reaction mixture. The specific free ion concentrations of Pb2+ and Ca2+, as well as Zn2+ and other divalent cations contained in the PKC reaction mixtures, were determined by 19F NMR spectroscopy. Using this approach to set and confirm the free Pb2+ and Ca2+ concentrations, we measured the Pb(2+)-dependent and the Ca(2+)-dependent activation of phosphotydylserine/diolein-dependent incorporation of 32P from ATP into histone and endogenous acid precipitable proteins in the 100,000 x g supernatant from homogenized rat brain cortex. We found that free Pb2+ activates PKC in the range from 10(-11) to 10(-8) M, Kact = 5.5 x 10(-11) M, while Ca2+ activates PKC in the range from 10(-8) to 10(-5) M, Kact = 2.56 x 10(-7) M. These findings clearly resolve the activation of PKC by subnanomolar concentrations of free Pb2+ from activation induced by Ca2+ or other divalent cations. Furthermore, it documents the utility of 5F-BAPTA as buffer and indicator when resolving the contributions of multiple divalent cations in biochemical processes.

Animals↗