Biokinetic modelling

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. 

The ICRP (1994b, 1995) developed a Human Respiratory Tract Model for Radiological Protection, which contains respiratory tract deposition and clearance compartmental models for inhalation exposure that may be applied to particulate aerosols of americium compounds. The ICRP (1986, 1989) has a biokinetic model for human oral exposure that applies to americium. The National Council on Radiation Protection and Measurement (NCRP) has also developed a respiratory tract model for inhaled radionuclides (NCRP 1997). At this time, the NCRP recommends the use of the ICRP model for calculating exposures for radiation workers and the general public. Readers interested in this topic are referred to NCRP Report No. 125 Deposition, Retention and Dosimetry of Inhaled Radioactive Substances (NCRP 1997). In the appendix to the report, NCRP provides the animal testing clearance data and equations fitting the data that supported the development of the human mode for americium. 

ICRP (1989) Americium Biokinetics Model Description of the model. 

Information on the transplacental transfer of americium in humans is not available directly, but the information from experiments with americium and other actinides has been used to derive biokinetic models and perform dosimetric models for the human (NCRP 1998 NRC 1996 Sikov and Kelman 1989). Studies in animals that received parenteral injections of americium have shown that absorbed americium is transferred to the fetus (Hisamatsu and Takizawa 1983 Paquet et al. 1998 Sasser at al. 1986 Schoeters et al. 1990 Weiss et al. 1980) (see Section 3.4.2.1). Limited reports indicate that241 Am may induce fetal death and teratogenic effects in rodents (Moskalev et al. 1969 Rommerein and Sikov 1986). 

Filipy RE, Khokhryakov VF, Suslova KG, et al. 1996. Comparisons of biokinetic models for actinide elements with observed tissue analysis data from occupationally-exposed humans of two countries. Health Phys 70(6)(Suppl.) S82. 

Kathren RL. 1994. Toward improved biokinetic models for actinides The United States Transuranium and Uranium Registries, a twenty-five year report. Rad Prot Dos 53(l-4) 219-227. 

Leggett RW, Eckerman KF, Williams LR. 1993. An elementary method for implementing complex biokinetic models. Health Phys 64(3) 260-271. 

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. 

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. 

Pharmacokinetic models have been developed that attempt to relate environmental levels to PbB levels (Leggett 1993 O Flaherty 1995). The Integrated Exposure Uptake Biokinetic Model (IEUBK) developed by EPA is one of the most extensive efforts to date to make population-based predictions of PbB levels based upon environmental data. The model incorporates both exposure/uptake parameters and a biokinetic component to estimate the PbB distribution in the exposed population (EPA 1994). 

The biokinetic modeling of physiological, pharmacological, and toxicological processes. 

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). 

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. 

Figure 2-8. Biokinetic Model for Uranium after Uptake to Blood...

Fisher et al. (1991) Biokinetic Model A modified biokinetic model for uranium was developed for inhaled soluble uranium based on human data from an accidental release of uranium hexafluoride in Oklahoma. Urinary excretion data from 31 exposed workers were used to test two previously published compartmental models for inhalation exposure to uranium (ICRP 1979 Wrenn et al. 1989). Urinary uranium was measured periodically for 2 years following the accident. Statistical analysis showed that the Wrenn et al. (1989) model produced a better fit to the excretion data than the ICRP (1979) model. 

Eisher Dr, Kathern RL, Swint MJ. 1991. Modified biokinetic model for uranium from analysis of acute exposure of UE6. Health Phys. 60(3) 335-342. 

Leggett RW. 1992. A generic age-specific biokinetic model for calcium-like elements. Radiat Protect Dosim 41 183-198. 

Building a Physiologically Based Biokinetic Model on the Basis of In Vitro-Determined Parameters... 

Blaauboer BJ (2010) Biokinetic modeling and in vitro-in vivo extrapolations. J Toxicol Environ Health B Crit Rev 13(2-4) 242-252... 

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