Biokinetics, lead

Preventive Measures. The intake uptake biokinetic model (lUBK) projects the impact of lead in the environment on blood lead. This model assumes conservatively high levels of intake and cannot account for chemical speciation, thus over-predictions of blood lead levels often occur. Nonetheless, because of the allegations of the impact of blood lead and neurobehavioral development, blood lead levels in children are being reduced adrninistratively to below 10 //g/dL. In order to do so, soil leads are being reduced to a level of between 500—1000 ppm where remediation is required. 

A Compartmental Model for Lead Biokinetics with Multiple Pool for Blood Lead... 

Kinetic Constants and Model Parameters in the O Flaherty Model 2-7 Residence Times in the Biokinetic Module of the IEUBK Model 2-8 Kinetic Constants and Model Parameters in the Leggett Model 2-9 Summary of Blood Slope Factors from Various Environmental Media 2-10 Genotoxicity of Lead In Vivo 2-11 Genotoxicity of Lead In Vitro... 

Numerous observations of non-linear relationships between PbB concentration and lead intake in humans provide further support for the existence of a saturable absorption mechanism or some other capacity limited process in the distribution of lead in humans (Pocock et al. 1983 Sherlock et al. 1984, 1986). However, in immature swine that received oral doses of lead in soil, lead dose-blood lead relationships were non-linear whereas, dose-tissue lead relationships for bone, kidney and liver were linear. The same pattern (nonlinearity for PbB and linearity for tissues) was observed in swine administered lead acetate intravenously (Casteel et al. 1997). These results suggest that the non-linearity in the lead dose-PbB relationship may derive from an effect of lead dose on some aspect of the biokinetics of lead other than absorption. Evidence from mechanistic studies for capacity-limited processes at the level of the intestinal epithelium is compelling, which would suggest that the intake-uptake relationship for lead is likely to be non-linear these studies are discussed in greater detail in Section 2.4.1. 

It does not contain a probabilistic modeling component that simulates variability therefore, it is not used to predict PbB probability distributions in exposed populations. Accordingly, the current version will not predict the probability that children exposed to lead in environmental media will have PbB concentrations exceeding a health-based level of concern (e.g., 10 pg/dL). Efforts are currently underway to explore applications of stochastic modeling methodologies to investigate variability in both exposure and biokinetic variables that will yield estimates of distributions of lead concentrations in blood, bone, and other tissues. 

The Integrated Exposure Uptake and BioKinetic (IEUBK) Model for Lead in Children is a classical... 

Species extrapolation. Data in both animals and humans (children and adults) describing the absorption, distribution, metabolism, and excretion of lead provide the biological basis of the biokinetic model and parameter values used in the IEUBK Model. The model is calibrated to predict compartmental lead masses for human children ages 6 months to 7 years, and is not intended to be applied to other species or age groups. 

Interroute extrapolation. The IEUBK Model includes an exposure module that simulates age-specific lead exposures via inhalation, and ingestion of lead in diet, dust, lead-based paint, soil, and water. The total exposure from each route is defined as the total lead uptake ( pg/day) over a 1-month period. Other routes of exposure may be simulated by the IEUBK Model pending available information from which to characterize both the exposure and media-specific absorption variables. Values for variables in the biokinetic component of the IEUBK Model are independent of the route of exposure. 

The Leggett Model simulates lead biokinetics in liver with two compartments the first simulates rapid uptake of lead from plasma and a relatively short removal half-life (days) for transfers to plasma and to the small intestine by biliary secretion a second compartment simulates a more gradual transfer to plasma of approximately 10% of lead uptake in liver. Different transfer rates associated with each compartment are calibrated to reproduce patterns of uptake and retention of lead observed in humans, baboons, and beagles following intravenous injection, as well as blood-to-liver concentration ratios from data on chronically exposed humans. Similarly, the Leggett Model simulates lead biokinetics in three compartments of soft tissues, representing rapid, intermediate, and slow turnover rates (without specific physiologic correlates). 

The kinetics of bone formation and remodeling are important factors in the overall biokinetics of lead. 

EPA. 1994a. Guidance manual for the integrated exposure uptake biokinetic model for lead in children. U.S. Environmental Protection EPA/540/R-93/081, PB93-963510. 

Hogan K, Marcus A, Smith R, et al. 1998. Integrated exposure uptake biokinetic model for lead in children empirical comparisons with epidemiological data. Environ Health Perspect 106 1557-1567. 

Kumar S, Mehta D, Singh S, et al. 1988. Biokinetics of lead in various mouse organs tissues using radiotracer technique. Ind J Exp Biol. 26 860-865. 

MahaffeyKR. 1990. Biokinetics of lead during pregnancy. Washington, DC Society of Toxicology. Paper No. 51. 

Exposure Uptake Biokinetic (IEUBK) model stochastic with probabilistic output sensitivity analysis lead exposure for children (6 months to 7 years old) across multiple pathways, routes, and environmental media, estimates blood lead concentrations (2005e)... 

USEPA (2005e) Integrated Exposure Uptake Biokinetic Model for Lead in Children, Windows version (lEUBKwin v1.0 build 263) (December 2005) 32-bit version. Washington, DC, United States Environmental Protection Agency (http //www.epa.gov/ superfund/programs/lead/products.htm software). 

Some 20% is assumed to enter the blood compartment. The ICRP biokinetic model for radium has the same general structure as that for strontium and uranium (see Figure 26.2-2). Bone is the critical organ with a biological half-life for radium in the range of 20 years. Since the decay of radium leads to the noble gas radon with a physical half-life of 3.8 days, most of the radioactivity of the decay product escapes from the body before further decays occur. 

In addition to a large database on lead exposures assembled empirically, a number of biokinetic models to ascertain exposure biomarkers and body lead burdens exist in the more recent lead literature, mainly in the form of such biomarkers of exposure as PbB. These predictive models of systemic lead exposure are of differing complexity and utility in diverse exposure settings. Historically, they can be defined as classical compartment models, a hybrid of the compartmental and physiologically based pharmacokinetic (PB-PK) models or the PB-PK model type. 

Chapter 7 presents the levels of lead intakes in various subsets of affected human populations. The term intake as employed in the book describes amounts of media-specific Pb inhaled or ingested per unit time, typically daily, that enter the chief receiving body compartments the gastrointestinal (GI) and respiratory tracts. Chapter 8 describes the biokinetics of Pb, specifically the toxicokinetics of Pb in human populations and the toxicokinetic basis of lead exposure biomarkers. It deals with the absorption (uptake) rate of Pb, subsequent distribution of the element into the body post-uptake, the rate of retention over the short and long term, and the rate of short- or long-term excretion of the substance. 

Concentrations of lead in the various environmental media described in this section are presented for extended periods. The available data that meet minimal statistical and measurement criteria generally only extend from the late 1960s/early 1970s to the present. The purposes of a wide temporal look at environmental lead concentrations are several. First, the nature of lead as an accumulating contaminant in the bodies of human populations requires an appreciation of the amounts of environmental lead that existed in past decades. As noted earlier, lead levels in media have been changing, mainly downward, so that current human body lead burdens are only partially quantifiable from current lead intakes into body compartments. Secondly, the use of predictive, biokinetic models of human lead exposures for simulating Ufe-time lead exposures requires knowledge of lead intakes from the earliest periods of life. 

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