Biokinetics

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. 

Blaauboer BJ (2003) Biokinetic and toxicodynamic modelling and its role in toxicological research and risk assessment. Altern Lab Anim 31(3) 277-281... 

The Human Respiratory Tract Model Absorption into Blood 3-6. ICRP (1989) Model of Americium Biokinetics 3-7. Leggett (1992) Model of Americium Biokinetics... 

Available information from human exposures indicates that airborne americium-containing particles are deposited in the respiratory tract, cleared to some extent via mucociliary action, and swallowed or expelled (Edvardsson and Lindgren 1976 Fry 1976 Newton et al. 1983 Sanders 1974 Toohey and Essling 1980). Descriptions of human respiratory tract models that can be used for radiation protection also include relevant information regarding biokinetics of inhaled particles (ICRP 1994b, 1995 NCRP 1997). Quantitative data are not available, however. Supporting animal studies include inhalation exposure to aerosols of americium (Buldakov et al. 1972 DOE 1978 Gillett et al. 1985 Sanders and Mahaffey 1983 Talbot et al. 1989 Thomas et al. 1972) or intratracheal instillation of americium compounds (Moushatova et al. 1996). 

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. 

The model, as described in Durbin and Schmidt (1985), does not have an intake component, but it could be linked to either an oral or inhalation intake model to simulate the biokinetics of americium associated with such exposures. 

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). 

Americium will occur in soil in the trivalent state. The transformations that may occur would involve complexation with inorganic and organic ligands (see Section 6.3.1) and precipitation reactions with anions and other substances present in the soil solution. The 241 Am occurring as an ingrowth progeny of 241Pu and trapped in a plutonium matrix will exhibit solubility and biokinetic characteristics of the plutonium, rather than americium. 

Carvalho FP, Fowler SW. 1985. Biokinetics of plutonium, americium and californium in the marine isopod Cirolcma borealis, with observations on its feeding and molting behavior. Mar Biol 89 173-181. 

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. 

Fisher NS, Bjerregaard P, Fowler SW. 1983. Interactions of marine plankton with transuranic elements 3. Biokinetics of americium in euphausiids. Mar Biol 75 261-268. 

Fowler SW, Carvalho FP. 1985. Americium biokinetics in benthic organisms as a function of feeding mode. Bull Environ Contain Toxicol 35 826-834. 

Harrison JD, Hodgson A, Haines JW, et al. 1993. The biokinetics of plutonium-239 and americium-241 in the rat after subcutaneous deposition of contaminated particles from the former nuclear weapons site at Maralinga Implications for human exposure. Hum Exp Toxicol 12 313-321. 

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. 

Moody JC, Stradling GN, Britcher AR. 1994. Biokinetics of three industrial plutonium nitrate materials Implications for human exposure. Radiat Prot Dosim 53(1-4) 169-172. 

Ramounet B. 1997. Biokinetics of Pu and Am after inhalation of industrial (U, Pu)02 and Pu02 in the rat Preliminary results. Radiat Prot Dosim 79(l-4) 53-56. 

Stradling GN, Stather JW, Gray SA, et al. 1994. Biokinetics of inhaled plutonium-239 and americium-241 present in contaminated dusts at Maralinga. Ann Occup Hyg 38(Suppl. l) 257-263. 

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... 

Table 2-7. Residence Times in the Biokinetic Module of the IEUBK Model...

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). 

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