Effective dose equivalent concept

Dose equivalent or rem is a special radiation protection quantity that is used, for administrative and radiation safety purposes only, to express the absorbed dose in a manner which considers the difference in biological effectiveness of various kinds of ionizing radiation. The ICRU has defined the dose equivalent, H, as the product of the absorbed dose, D, and the quality factor, Q, at the point of interest in biological tissue. This relationship is expressed as H = D x Q. The dose equivalent concept is applicable only to doses that are not great enough to produce biomedical effects. 

The calculation of effective dose equivalent is sometimes used even when reporting values for natural radioactivity. The concept of effective dose equivalent was developed for occupational exposures so that different types of exposure to various organs could be unified in terms of cancer risk. It is highly unlikely that the general population would require summation of risks from several sources of radiation exposure. 

B.5.3 Effective Dose Equivalent and Effective Dose Equivalent Rate. The absorbed dose is usually defined as the mean absorbed dose within an organ or tissue. This represents a simplification of the actual problem. Normally when an individual ingests or inhales a radionuclide or is exposed to external radiation that enters the body (gamma), the dose is not uniform throughout the whole body. The simplifying assumption is that the detriment will be the same whether the body is uniformly or nonuniformly irradiated. In an attempt to compare detriment from absorbed dose of a limited portion of the body with the detriment from total body dose, the ICRP (1977) has derived a concept of effective dose equivalent. 

The SITP is a quantity derived from the Annual Limit on Intake (ALI), an internationally accepted concept that has been acknowledged by the Government s Radioactive Waste Management Committee (RWMAC) as a valid method of establishing equivalent hazards of different waste types. The ALI is a derived limit for the permissible amount of radioactive material taken into the body of an adult radiation worker by inhalation or ingestion in a year. The ALI is the smaller value of intake of a given radionuclide in a year by the reference man that would result in either a committed effective dose equivalent of 0.05 Sv or 0.5 Sv to any individual organ or tissue. 

Key CPZ equiv dose = Chlorpromazine equivalent dose.This concept is of value in comparing the potency of classical antipsychotics. Dose ranges are not specified as they are extremely wide and drugs are normally titrated up from low starting doses (e.g. chlorpromazine 25 mg or equivalent) until an adequate antipsychotic effect is achieved or the maximum dose reached.The chlorpromazine equivalent dose concept is of less value for atypical antipsychotics since minimum effective doses (Min. eff. dose) and narrower therapeutic ranges have been defined. Maximum dose (Max. dose) can be exceeded only under specialist supervision. 

For radiation protection purposes, several theoretical dosimetric quantities have been created that attempt to normalize the responses of different tissues and organs of the body from irradiation by different types of ionizing radiation so that uniform radiation protection guidelines can be promulgated that are insensitive to the particulars of any given irradiation scenario. The traditionally used quantity has been the dose equivalent (DE), which is defined as the absorbed dose (D) multiplied by the quality factor Q. The unit of dose equivalent has been the rem, which is dimensionally the same as the rad the SI unit is the Sievert (Sv). Recently, the DE has been replaced by a similar concept called the equivalent dose. The equivalent dose depends on the relative biological effectiveness rather than on Q. 

The importance of spacers and all techniques to improve delivery is relative. If the dose delivered the old way achieves maximum pharmacodynamic effect, improving delivery is moot [53]. This observation raises other questions about aerosol drug delivery, namely, the effective dose. It is likely that the dose overkill concept has been the reason for failure to show differences when some applications were compared. A new, refined device may not be more effective than an older one because the older one delivers such a large dose that, despite inefficiency, it is pharmacodynamically equivalent. At least one study shows no difference in protection from exercise-induced asthma by nedocromil sodium and by sodium cromoglycate via MDI, and use of a spacer did not change results [54]. 

The consequences of accidents are expressed in terms of dose, which can be calculated using standard atmospheric dispersion and dose calculation software, such as those based on the Canadian standard (CSA, 1991). Stochastic doses are usually expressed in terms of the effective and thyroid doses for emergencies that involve the release of radioactive iodine. For emergencies that do not involve iodine, the critical organ dose would be based on the main radionuclide most likely to be released. For the calculation of deterministic health effects, it is important to use organ-specific equivalent doses because the effective dose concept is not applicable to doses this high. It is also important to consider the rate at which the dose is received because the thresholds for deterministic effects vary with the exposure rate. 

An alternative approach to risk estimation is to relate the mutagenicity of a chemical to the amount of radiation that would produce an equal effect. This approach is best exemplified by the concept of a rem-equivalent chemical (REC). A REC is the dose (concentration times time) that produces an amount of genetic damage equal to that produced by 1 rem of chronic radiation.98 REC was introduced, not as a basis of risk estimation, but as a guide to setting standards.1 0 80 There were already accepted radiation standards, and it was thought that chemical risks could be considered by the same standards if the chemical damage could be correlated with that from radiation. 

All components behave as if they were simple dilutions by a factor g of this first chemical hence, all concentrations of component 2. .. n can be rescaled to the first chemical, independent of the considered effect level. A widely used application of this approach is the toxic equivalence factor (TEF) concept for the assessment of mixtures of polychlorinated dioxins and furans (PCDDs/Fs). Here, concentrations (or doses) of specific PCDD/F isomers are all expressed in terms of the concentration of a reference chemical, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), needed to induce the same effect ( equivalent or equi-effective concentration). The assessment of the resulting combined effect is obtained simply by adding up all TCDD-equivalent concentrations. 

Additivity and no interactions. Additivity concepts that explain a shared adverse effect across chemicals include dose or concentration addition, which assumes chemicals share a common toxic MOA, and RA, which assumes chemicals act by toxicologically (and thus also statistically) independent MOA. There is also a body of research on the use of statistical dose-response modeling of empirical data to examine the joint toxic action of defined mixtures where the claim is that MOA assumptions are not necessary (Gennings et al. 2005). Dose addition methods scale the component doses for relative toxicity and estimate risk using the total summed dose, for example, using relative potency factors (RPFs), toxicity equivalency factors (TEFs), or a hazard index (HI). In contrast, RA (also named independent action ) is... 

The CA concept uses the toxic unit (TU) or the toxicity equivalence factor (TEF), defined as the concentration of a chemical divided by a measure of its toxicity (e.g., EC50) to scale toxicities of different chemicals in a mixture. As a consequence, the CA concept assumes that each chemical in the mixture contributes to toxicity, even at concentrations below its no-effect concentrations. The IA or RA concept, on the other hand, follows a statistical concept of independent random events it sums the (probability of) effect caused by each chemical at its concentration in the mixture. In the case of IA, the only chemicals with concentrations above the no-effect concentration contribute to the toxicity of the mixture. The IA model requires an adequate model to describe the (full) dose-response curve, enabling a precise estimate of the effect expected at the concentration at which each individual chemical is present in the mixture. The concepts generally are used as the reference models when assessing mixture toxicity or investigating interactions of chemicals... 

The existing methods available for scientifically defensible risk characterization are not yet ideal since each step has an associated uncertainty resulting from data limitation and incomplete knowledge on exact mechanism of action of the toxic chemical on the human body. For noncancer end points, safety factors or uncertainty factors are applied since these effects are assumed to have a threshold below which no adverse effect is expected to be observed. US EPA has used the concept of a reference concentration (RfC) to estimate acceptable daily human exposure from HAPs. The RfC was adapted for inhalation studies based on a reference dose (RfD) method previously used for oral exposure assessment. The derivation of the RfC differs from that for the RfD in the use of dosimetric adjustment to extrapolate the exposure concentration for animals to a human equivalent concentration. Both are estimates, with uncertainty spaiming perhaps an order of magnitude, of a daily exposure to the human population, including sensitive subgroups, which would be without appreciable risk of deleterious effects over a lifetime. 

Because of the varying radiation sensitivities of the different cell types, a tissue weighing factor, Wj, is introduced. It represents the relative contribution of that tissue to the total detriment from uniform irradiation of the body Table 18.6 gives tissue weighing factors. This leads to another dose concept (cf. eqn. 18.1), the effective equivalent dose, 0g, which is the sum of the weighted equivalent doses in all tissues, as given by... 

---