Dosing calculations

Models for transport distinguish between the unsaturated zone and the saturated zone, that below the water table. There the underground water moves slowly through the sod or rock according to porosity and gradient, or the extent of fractures. A retardation effect slows the motion of contaminant by large factors in the case of heavy metals. For low level waste, a variety of dose calculations are made for direct and indirect human body uptake of water. Performance assessment methodology is described in Reference 22. 

Doses calculated in animals are converted to equivalent doses in humans on the basis of comparative physiological considerations (c.g., ventilatory parameters and regional lung surface areas). Additionally, if the e.xposure period was discontinuous, it is adjusted to reflect continuous e.xposure. 

After a baseline angiogram confirms the presence and location of the vascular occlusion, a microcatheter is navigated over a microwire into the occluded vessel, traversing the thrombus. Once the microcatheter is positioned immediately distal to the clot, thrombolytic infusion begins the microcatheter is then pulled back through the clot while dmg is infused. Dose adjustments and total dose calculations are made depending on the clinical circumstances, pretreatment dose of rt-PA received, degree of recanalization, and relative size and function of the territory at risk. 

If an inhalation study in animals, list the conversion factors used in determining human equivalent dose Calculations 200 ppm X 7/24 hr X 1/30 UF = 1.94 ppm. 

Fig. 15 Spreadsheet illustrating the calculation of plasma concentrations after multiple extravascular doses, calculated using Eq. (56).

The range of doses calculated when only basal cells are assumed at risk is also shown in Figure 5. For unattached daughters, doses are approximately one half and for attached daughters three quarters of values derived by averaging over all cells. These doses are to be compared with the range derived by the NEA (NEA, 1983). The reference values recommended by the NEA and adopted by UNSCEAR (UNSCEAR, 1982) lie at the bottom of the range of doses to basal cells derived here. 

Hofmann, W., Dose Calculations for the Respiratory Tract from Inhaled Natural Radionuclides as a Function of Age - II. Basal Cell Dose Distributions and Associated Lung Cancer Risk, Health Phys. 43 31-44 (1982). 

The tracheobronchial dose has been calculated previously using average reported values for the various factors needed (Harley, 1984). The following list of factors involved in the dose calculation indicates where differences in the modeling occurs for this update. 

The specific values of the physical and biological characteristics such as breathing patterns for occupational exposure and active and resting patterns for environmental exposure are given in the footnotes to the Tables. A few remarks should be made concerning the parameters used which affect the dose calculation significantly. 

Dosimetric Studies. The main objective of Rn-d dosimetry is to enable the assessment of the observed dose from Rn-d deposited in the respiratory tract from measured Rn-d concentration in the atmosphere. As a consequence of an inhomogeneous Rn-d deposition within the lung, different dosimetric concepts have been developed to describe either regional mean dose values (e.g. for tracheobronchial or pulmonary region) or microdosimetric dose calculations (e.g. for the basal cell layer). Using Monte Carlo calculation methods it is also possible to account for the random nature of cellular hits by deposited alpha particles. The results of such dosimetric calculations should provide the following information needed for Rn-d risk assessment ... 

Pohl, E., and J. Pohl-Ruling, Dose Calculations Due to the Inhalation of Rn 222, Rn 220 and Their Daughters, Health Physics 32 552-555 (1977). 

SC-25 Radiation Protection in the Use of Small Neutron Generators SC-26 High Energy X-Ray Dosimetry SC-32 Administered Radioactivity SC-33 Dose Calculations... 

Wessels, B.W., and Rogus, R.D. (1984) Radionuclide selection and model absorbed dose calculations for radiolabeled tumor associated antibodies. Med. Phys. 11, 638-645. 

LD50 Lethal dose 50 The dose calculated to kill 50% of a subject... 

First, the procedure now used by the EPA for inhalation data differs from what we have described above, in that the ten-fold factor for interspecies extrapolation (animal-to-human) is dropped in favor of a specific model that describes the well-known physiological differences between animals and humans that affect the relative rates of movement of a given administered dose of a chemical in the respiratory tracts of animals and humans. These physiological models provide fairly accurate predictions of the relative doses of chemicals delivered into the respiratory regions of animals and humans who have received identical administered (inhaled) doses. The estimate of delivered dose offers a well-accepted scientific approach to at least part of the problem of interspecies differences. Details of the delivered dose calculations are beyond the scope of this book (see references in Sources and recommended reading). 

For the theophylline example given in Example Maintenance Dose Calculation, the loading dose would be 350 mg (35 L x 10 mg/L) for a 70-kg person. For most drugs, the loading dose can be given as a single dose by the chosen route of administration. 

When intermittent doses are given, the loading dose calculated from equation (12) will only reach the average steady-state concentration and will not match the peak steady-state concentration (Figure 3-6). To match the peak steady-state concentration, the loading dose can be calculated from equation (13) ... 

Give a loading dose or maintenance dose calculated from TC, Vd, and CL. 

Mathematical modelling of the dose-response relationship is an alternative approach to quantify the estimated response within the experimental range. This approach can be used to determine the BMD or benchmark concentration (BMC) for inhalation exposure, which can be used in place of the LOAEL or NOAEL (Crump, 1984). The BMD (used here for either BMD or BMC) is defined as the lower confidence limit on a dose that produces a particular level of response (e.g., 1%, 5%, 10%) and has several advantages over the LOAEL or NOAEL (Kimmel Gaylor, 1988 Kimmel, 1990 USEPA, 1995 IPCS, 1999). For example, (1) the BMD approach uses all of the data in fitting a model instead of only data indicating the LOAEL or NOAEL (2) by fitting all of the data, the BMD approach takes into account the slope of the dose-response curve (3) the BMD takes into account variability in the data and (4) the BMD is not limited to one experimental dose. Calculation and use of the BMD approach are described in a US EPA... 

The ratios of molecular weights for these ethyl homologues, 314 for the phosphate (CEY-19), the same for the sulfate (by the way, it s not yet explored in man, to my knowledge), 276 for the acetate and 234 for the free phenol (CZ-74), all fall into a pretty narrow range, from about 4 to 3. So, the weight of the ester component in the actual molecule being considered is a relatively minor factor in the dose calculation. I am at peace with the hypothesis that all four compounds are interchangeable in potency. 

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