Biologies dose calculations

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. 

Numerous mathematical models have been developed in attempts to estimate potential risks to humans from low-dose exposures to carcinogens. Each model incorporates numerous unverifiable assumptions. Low-dose calculations are highly model dependent, widely differing results are commonly obtained, and none of the models can be firmly justified on either statistical or biological grounds (22). Thus, the decision to use this approach and the choice of how to do the calculations are matters of judgment. Among the choices that the decision makers must consider are which model(s) to employ, which assumptions to incorporate, and which acceptable risk to allow. 

B. G. Schnitzler, A Calculational Method for Determining Biological Dose Rates from Irradiated Research Reactor Fuel, NUREG-CR-4203, April 1985. 

The proportion of ionized and unionized forms of a chemical compound can be readily calculated according to the above equation. It can be easily seen that pK is also a pH value at which 50% of the compound exists in ionized form. The ionization of weak acids increases as the pH increases, whereas the ionization of weak bases increases when the pH decreases. As the proportion of an ionized chemical increases, the diffusion of the chemical through the biological membranes is greatly impaired, and this attenuates toxicokinetic processes. For example, the common drug acetosalicylic acid (aspirin), a weak acid, is readily absorbed from the stomach because most of its dose is in an unionized form at the acidic pH of the stomach. 

The calculation of potential total dermal exposure of mixer-loaders and re-entry workers using dosimetry data and calculation of the internal dose using biological monitoring data is complex but will be discussed briefly. 

Dose Equivalent (DE)—A quantity used in radiation safety practice to account for the relative biological effectiveness of the several types of radiation. It expresses all radiations on a common scale for calculating the effective absorbed dose. It is defined as the product of the absorbed dose in rad and certain modifying factors. (The unit of dose equivalent is the rem. In SI units, the dose equivalent is the sievert, which equals 100 rem.)... 

RBE is used to denote the experimentally determined ratio of the absorbed dose from one radiation type to the absorbed dose of a reference radiation required to produce an identical biologic effect under the same conditions. Gamma rays from cobalt-60 and 200-250 keV x-rays have been used as reference standards. The term RBE has been widely used in experimental radiobiology, and the term quality factor used in calculations of dose equivalents for radiation safety purposes (ICRP 1977 NCRP 1971 UNSCEAR 1982). RBE applies only to a specific biological end point, in a specific exposure, under specific conditions to a specific species. There are no generally accepted values of RBE. 

Example. Sulfadiazine in a normal volunteer had a biological half-life of 16 hours and a volume of distribution of 20 L. Sixty percent of the dose was recovered as unchanged drug in urine. Calculate TCR, RCR, and MCR for sulfadiazine in this person. 

Example. A drug has a biologic half-life of 4 hours. Following an IV injection of 100 mg, is found to be 10 pg/mL. Calculate Cmax and Cm n if the 100-mg IV dose is repeated every 6 hour until a plasma concentration plateau is reached. 

SC-52 Conceptual Basis of Calculations of Dose Distributions SC-53 Biological Effects and Exposure Criteria for Radiofrequency Electromagnetic Radiation... 

The following data was obtained after the administration of a single 500-mg dose of a drug by slow intravenous infusion. Calculate the AUC, elimination rate constant, and the biological half-life of the drug. 

To deterniine the risks in the area of human health (workers, consumers, including the absorption of chemicals from the environment) the concentration of a substance is ascertained for so-called end points in the human body (organs or biological systems). The measured or calculated concentration (exposure level) is compared with the NOAEL (No Observed Adverse Effect Level). The NOAEL is the highest concentration at which no more effect is observed (usually in animal testing), i.e. there is no visible or measurable effect. If such a levef cannot be detected, the LOAEL (Lowest Observed Adverse Effect Level) can be applied instead. This is the value at which the effect first becomes visible or measurable with an increasing dose. 

The major urinary metabolite of di(2-ethylhexyl) adipate, 2-ethylhexanoic acid, has been shown to be an appropriate marker for biological monitoring of dietary di(2-ethylhexyl) adipate intake (Loftus etal., 1993, 1994). A limited population study in the United Kingdom was undertaken to estimate the daily intake of di(2-ethylhexyl) adipate following intake of a mean dose of 5.4 mg di(2-ethylhexyl) adipate presented with food. The study involved the determination of the urinary metabolite, 2-ethyl-hexanoic acid (24-h mine sample) in 112 individuals from five geographical locations. A skewed distribution with a median value for the daily intake of 2.7 mg was determined (Loftus et al., 1994). This value is about one third of the indirectly estimated maximum intake of 8. 2 mg per day. The probability of a daily intake in excess of 8.2 mg in the limited population (112 individuals) was calculated to be 3% (Loftus etal, 1994). 

It is now usual to calculate the effective dose equivalent (Appendix 1.2). The dose equivalent measured in Sieverts (Sv), takes into account the relative biological efficiency of different radiations. For gamma and beta radiation, the conversion factor is unity, but for alpha radiation it is 20. The effective dose equivalent allows also for the relative importance of irradiation of various organs to the risk of cancer. To convert thyroid dose from beta particles, measured in Gy, to effective dose equivalent, a factor 0.03 is applied. Thus the maximum thyroid doses estimated by Loutit et al. correspond to effective dose equivalents of 4.8 mSv (child) and 1.2 mSv (adult). Adding the external whole body gamma radiation, for which the conversion factor is unity, gives 5.4 mSv (child) and 1.8 mSv (adult). 

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