Dosing modeling

Latent cancer is calculated to be the primary risk from a nuclear accident (this may be due to the conservatism in the low-dose models). At Chernobyl, most of the deaths were from fire and impact. Chemical process risk depends on the chemicals being processed. Experience shows that processing poisons poses the highest risk to public and workers. 

Howci cr, this linear equation is valid only at low risk levels (i.e., below estimated risks of 0.01). For situations where chemical intakes might be liigh (i.e., risk above 0.01), an altcrmilc equation should be used. The one-liit equation, which is consistent with the linear low-dose model given above and described below, should be used instead. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological or epidemiological data to calculate a BMD. 

If linear (dose) models without thresholds are to be used for carcinogen (or other) risk assessment, estimation of exposure at specified levels becomes irrelevant to risk assessment or, at least, its use is nonintuitive. For example, a carcinogen risk analysis may be based on a linear, nonthreshold health effects model. The total health risk would thus be proportional to the long-term exposure summed for all affected people for the identified period, and exposure of many people at low concentrations would be equivalent to exposure of a few to high concentrations. The atmospheric dispersion that reduces concentrations would also lead to exposure of more people therefore, increments... 

This inverse relationship between equilibrium factor and "unattached" fraction and their relationship to the resulting dose is important in considering how to most efficiently and effectively monitor for exposure. This inverse relationship suggests that it is sufficient to determine the radon concentration. However, it is not clear how precisely this relationship holds and if the dose models are sufficiently accurate to fully support the use of only radon measurements to estimate population exposure and dose. 

However, results obtained from lung dose modelling still show a large range of values for the conversion of Rn-d exposure to dose for the following reasons ... 

Hartzell, G.E. Emmons, H.W. "The Fractional Effective Dose Model for Assessment of Hazards Due to Smoke from Materials," J. Fire Sciences 1988, 6(5), 356-362. 

Kubota K, Dey F, Matar SA, Twizell EH (2002) A repeated-dose model of percutaneous drug absorption. Appl Math Model 26 529-544. 

Georgievsky V. Ecological and dose models in radiation accidents, 1994. - 236 p. 

The depth-dose model allows the gel energy Eg of a resist to be calculated from an observed interface gel dose Dg under conditions of zero backscatter and predicts a dependence of Dg on accelerating voltage going as which agrees reasonably well with experiments. Calculations of... 

The US-EPA Consolidated Human Activity Database (CHAD) (US-EPA 2007b) contains data obtained from preexisting human activity studies that were collected at city, state, and national levels. CHAD is intended to be an input file for exposure/intake dose modeling and/or statistical analysis. CHAD is a master database providing access to other human activity databases using a consistent format. This facilitates access and retrieval of activity/and questionnaire information from those databases that US-EPA currently has access to and uses in its various regulatory analyses undertaken by program offices. 

Calculation of G -values from the results shown in Figures 2 and 3 requires determining the amount of dose absorbed in the film for a given incident dose. Bowden (7) has shown, using the depth-dose model of Heidenreich, (9) an accurate measure of the energy absorbed in a polymer film can be determined. An example of such a calculation for polystyrene is given in the appendix. 

For the most frequently used low-dose models, the multi-stage and one-hit, there is an inherent mathematical uncertainty in the extrapolation from high to low doses that arises from the limited number of data points and the limited number of animals tested at each dose (Crump et al., 1976). The statistical term confidence limits is used to describe the degree of confidence that the estimated response from a particular dose is not likely to differ by more than a specified amount from the response that would be predicted by the model if much more data were available. EPA and other agencies generally use the 95 percent upper confidence limit (UCL) of the dose-response data to estimate stochastic responses at low doses. 

Low-dose extrapolation models are the backbone of dose-response assessments. Because they can play such a dominant role in the regulatory process, it is important to understand some of their characteristics. As shown in Figure 3.10, different extrapolation models usually fit the data in the observable dose region in animal tests about equally well (Krewski et al., 1989), but they often give quite different results in the unobserved low-dose region of interest in assessments of risk to human health. The results obtained by extrapolation of the most commonly used low-dose models usually vary in a predictable manner, because the models use different mathematical equations to describe the chemical s likely behavior in the low-dose region. 

Models use mathematical expressions to quantify the processes leading to exposure and dose. Models that predict dispersion, fate, transport, and transfer of chemicals are based on physical and chemical principles. Models that describe activities of individuals as they interact with the environment are based on statistical data from observational measurement studies. In Figure 13, the processes that must be accounted for from source to dose are described the text above the orange boxes shows the types of models that can be used to quantify these processes. These models can be applied to predict exposure and dose for an individual however, they are most effectively applied at the population level (IPCS, 2005). 

IPCS (2000) Human exposure and dose modelling. In Human exposure assessment. Geneva, World Health Organization, International Programme on Chemical Safety (Environmental Health Criteria 214 http //www.inchem.Org/documents/ehc/ehc/ehc214.htm PartNumber 6). 

In order to determine variation in PBLx intake resulting from the variance (due to uncertainty and variability) in the parameters used to describe the source-to-dose model, we first use the... 

Both Models 107 for benzene and 108 for multiple chemicals are based on the Benzene Exposure Assessment Model (BEAM) (Behar et al 1993) to generate benzene or chemical inhalation exposure profiles for different human subgroups. For an estimation of dermal dose, Model 109 is a simple film-thickness -based model like DERMAL (Versar, Inc., 1995). Model 110 estimates multiple pathways exposure (i.e. inhalation and dermal doses) to multiple chemicals from the use of consumer products. 

Smith JM, Tang CM, Van Noorden S, Holden DW Virulence of Aspergillus fumigatus double mutants lacking restrictocin and an alkaline protease in a low-dose model of invasive pulmonary aspergillosis. Infect Immun 1994 62 5247-5254. 

Two examples of alternative approaches to cancer risk assessment would be estimations based on threshold-response (EPA, 2005a) and benchmark dose modeling (EPA, 1995, 2000). As a practical matter, if the proposed basis of safety relies on a threshold or mode-of-action characterization to dismiss or mitigate animal tumor data, PDA would reconunend that the safety narrative clearly discuss the scientific rationale and present all relevant data for consideration. In the absence of adequate evidence to the contrary, PDA presumes that certain assumptions are appropriately protective of safety, namely that (i) the induction of tumors in animals is relevant to human... 

Lioy P New Jersey University of Environmental and Occupational Health Sciences Institute, Piscataway NJ Refinement of exposure/dose models. Comparison of bioavailability of elemental waste laden soils using in vivo and in vitro analytical methodology DOE... 

The names of some dose models are LADTAP GENII MICRO AIRDOS. 

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