Mohamed Abdallah, University of Birmingham, United Kingdom Geza Benke, Monash University, Australia Mark F. Cesta, National Institute of Environmental Health Sciences, USA Melissa Friesen, National Cancer Institute, USA Dori Germolec, National Institute of Environmental Health Sciences, USA Keith Houck, U.S. Environmental Protection Agency, USA Gaku Ichihara, Tokyo University of Science, Japan Charles William Jameson, CWJ Consulting, LLC, USA Jun Kanno, Japan Organization of Occupational Health and Safety, Japan Hans Kromhout, Utrecht University, The Netherlands M. Matilde Marques, University of Lisbon Igor Pogribny, National Center for Toxicological Research, USA Consolato Maria Sergi, University of Alberta, Canada Camilla Svendsen, Norwegian Institute of Public Health, Norway

IARC Monographs on the evaluation of carcinogenic risks to humans; dry cleaning, some chlorinated solvents and other industrial chemicals.

Principles and recent developments in chelation treatment of metal intoxication.

The stable lead isotope methodology can be used to study the release of lead from bone into the circulation because of its potential to distinguish circulatory lead from "older" and isotopically different skeletal lead that may have been accumulated years or decades earlier. Here we report the initial results from a larger ongoing study that evaluates the skeleton as a source of lead to the circulation in environmentally exposed human subjects. Lead concentrations and stable lead isotopic compositions were measured in blood and trabecular bone samples obtained from five patients who underwent total hip or knee joint replacement. All subjects contained low blood (1-6 micrograms/dl) and bone (0.6-7 micrograms/g dry weight) lead concentrations typical of environmentally exposed individuals. There were relatively large differences in the lead isotopic compositions between the paired blood and bone samples from each subject. These isotopic differences are attributed to differences in the lead isotopic compositions of past versus current lead exposures and to the long elimination half-life of lead in the skeleton compared to lead in the circulation. Based on these data, we determined that the skeleton contributed 40-70% of the lead in the blood of these subjects. This initial study demonstrates the utility of the stable lead isotope methodology for investigating the release of lead from the skeleton. It also shows that the skeleton can be an important endogenous source of lead exposure in environmentally exposed humans.

Use of endogenous, stable lead isotopes to determine release of lead from the skeleton.

The importance of accurate measurements of environmental lead exposure and toxicity is substantiated by analyses documenting the global contamination of the biosphere with industrial lead and the pervasiveness of measurable lead toxicity in human populations. Those data demonstrating environmental lead contamination and toxicity have, in part, led to regulations that limit the amount of lead in some products (e.g., paint, solder, and gasolines) in many industrialized countries. These regulations have resulted in a substantial reduction in some lead discharges to the environment. In spite of these reductions, current environmental lead levels are still often more than 10-fold, and sometimes more than 10,000-fold, higher than natural levels. Further, environmental lead concentrations are expected to remain elevated for a protracted period due to continued emissions of relatively large amounts of industrial lead to the environment and the persistence of contaminant lead in the environment. Discharges of contaminant lead have resulted in increases in organism and human lead levels comparable to increases documented in environmental matrices, as indicated by a recent estimate of the natural level of lead in blood of preindustrial humans (0.016 microgram/dL or 0.8 nM). This estimate is 175-fold lower than average blood lead levels in the United States (2.8 micrograms/dL or 140 nM) and 600-fold lower than the recently (1991) revised Centers for Disease Control (CDC) action level of concern for early toxic effects in children (10 micrograms/dL or 480 nM). The significance of these comparisons to public health is corroborated by numerous studies suggesting that there may be no lower threshold for sublethal toxicity in contemporary (i.e., lead-contaminated) humans. Those data also indicate that environmental lead concentrations that were previously considered innocuous may be deleterious to human health. It is apparent that the extent of sublethal lead toxicity in humans may be best addressed by studies that consider control populations possessing natural (i.e., preindustrial) lead burdens, as well as state-of-the-art, trace-metal-clean techniques and advanced instrumentation. Trace-metal-clean techniques are required to prevent the inadvertent lead contamination of samples, which has plagued many previous analyses of environmental and human lead levels. Advanced instrumentation is required to provide the sensitivity, accuracy, and precision that are needed to quantify the sublethal effects of lead concentrations at environmental levels of exposure. Fortunately, methodologies utilizing these advancements are now capable of addressing many of the important issues (e.g., lead biomolecular speciation, low exposure effects) in environmental and human lead toxicology.

Measurements of environmental lead contamination and human exposure

Stable lead isotopes in environmental health with emphasis on human investigations.

The Effects of Succimer on the Absorption of Lead in Adults Determined by Using the Stable Isotope 204Pb

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The Effects of Succimer on the Absorption of Lead in Adults Determined by Using the Stable Isotope 204Pb