Biokinetic models structure

White PD, Van Leeuwen P, Davis BD, et al. 1998. The conceptual structure of the integrated exposure uptake biokinetic model for lead in children. Environ Health Perspect 106 1513-1530. 

An integrated testing strategy is any approach to the evaluation of toxicity which serves to reduce, refine or replace an existing animal procedure, and which is based on the use of two or more of the following physicochemical, in vitro, human (e.g., epidemiological, clinical case reports), and animal data (where unavoidable), and computational methods, such as (quantitative) structure-activity relationships ([Q]SAR) and biokinetic models. 

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. 

Much of the interest in using predictive modeling of human Pb exposures concerns mechanistic, i.e., biokinetic, models. Biokinetic models differ from site-specific or multisite ad hoc/slope factor models in a number of important ways. Eirst, they are constructed (by definition) within a computational and biological/kinetic framework. That framework specifies inclusion of all identified parameters representing mechanisms by which environmental Pb is deposited in and removed from human organs and tissues. Mechanistic models are structured to be much more complex than the regression models... 

FIGURE 9.4 Structure of the O Flaherty lead exposure biokinetic model. Conceptualized by U.S. EPA (2006) from O Flaherty (1993, 1995). 

Review of the Uptake Biokinetic (UBK) Model for Lead, Report No. EPA SAB-IAQC-92. White, P.D., Van Leeuwen, P., Davis, B.D., Maddalonr, M, Hogan, KA., Marcus, A.H., et al., 1998. The conceptual structure of the Integrated Exposure Uptake Biokinetic Model far lead in children. Environ. Health PerspecL 106 (SuppL 6), 1513—1530. 

Single-shot, i.e., isolated blood lead, surveys have been employed in a number of lead-impacted U.S. communities. Some of these efforts have been carried out in areas where the U.S. EPA has done biokinetic modeling of lead exposure via the EPA lEUBK model. One needs to be careful about calibrating EPA s model or any other biokinetic model on haphazard, i.e., unstructured, PbB surveys. The merits and limits of such surveys have been critiqued elsewhere (Mushak, 1998). The problems are several (1) such measures may be affected by various artifacts that are less influential in more structured sampling and (2) such measures relate to bioavaUability at some specific point in time and with a certain current land-use practice and population distribution. Demographic or socioeconomic characteristics of affected populations could change over time with movements in and out of areas of... 

Until recently, reactor design, selection of suitable operating conditions, and scale up were performed using either rules of thumb [80] or different kinds of compartment models [36,81 -83].With the exponential increase in computing power, hard- and software tools became available to successfully implement simulation strategies based on integration of computational fluid dynamics (CFD) and structured biokinetics. 

The biokinetic component of the lEUBK model simulates Pb distribution to blood and other tissues and also the excretion of the toxicant, the latter mainly via urine and feces, and also by such minor routes as skin, nails, and hair. Conceptually and structurally, the model s biokinetic underpinning is a com-partmental structure in which aU compartments are taken to be kinetically homogeneous. Figure 9.3 graphically identifies seven compartments among which Pb transfers occur, including a central blood plasma—extracellular fluid (ECF) compartment, an erythrocyte compartment, five peripheral body compartments, and three excretion pools (White et al., 1998). Two of the compartments important to Pb deposition and release are subcompartments of bone trabecular... 

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