Fractional effective dose

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. 

The Fractional Effective Dose (FED) of toxicant received by an exposed person is defined by Hartzell (5.6) as... 

Figure 10. The percent probability of incapacitation or death as dependent on the corresponding Fractional Effective Dose (FED) defined by Equation 1.

The general approach in generating toxic potency data from chemical analysis is to assume additive behavior of individual toxicants, and to express the concentration of each toxicant as its fraction of the lethal concentration for 50% of the population for a 30 min exposure (LC50). Thus an fractional effective dose (FED) equal to one indicates that the sum of concentrations of individual species will be lethal to 50% of the population over a 30 min exposure. Two equations have been developed for the estimation of the FED for lethality from the chemical composition of the environment in the physical fire model. Each begins with the precept that the fractional lethal doses of most gases are additive, as developed by Tsuchiya and Sumi.32... 

Recently, water-soluble protein fractions, isolated from extracts of bone matrix, were incorporated into a collagen matrix and shown to induce bone (67,68) and cartilage formation both in vitro and in vivo (69,70). In the latter studies, in the absence of the collajgen delivery system, the proteins were incapable of inducing cartilage formation in vivo when implanted intramuscularly into mice. The success of this approach appears to depend on delivering the active agents at an effective dose over an extended time period. 

Although the pH-partition hypothesis and the absorption potential concept are useful indicators of oral drug absorption, physiologically based quantitative approaches need to be developed to estimate the fraction of dose absorbed in humans. We can reasonably assume that a direct measure of tissue permeability, either in situ or in vitro, will be more likely to yield successful predictions of drug absorption. Amidon et al. [30] developed a simplified film model to correlate the extent of absorption with membrane permeability. Sinko et al. [31] extended this approach by including the effect of solubility and proposed a macroscopic mass balance approach. That approach was then further extended to include facili-... 

Thus, the fraction of dose absorbed is exponentially related to the absorption number. Equation (10) shows that the absorption number (and therefore the membrane permeability) is a fundamental parameter while other parameters such as the partition coefficient and pKa are useful guides but not fundamental parameters. For highly soluble drugs with linear absorption kinetics, dose and dissolution have no effect on the fraction of dose absorbed. In the case of drugs that are absorbed by a carrier-mediated process, a mean permeability should be used [30],... 

Figure 10 The fraction of dose absorbed as a function of the effective human permeability. (---) Compartmental absorption and transit model (Eqs. (59) or (60)) (—) single-...

EUSES. As in the case of USEtox model, the present model provides outputs such as human intake fraction of a certain substance for different exposure pathways. In the present case study, estimation of the human intake doses for Guiyu was calculated. These results were compared with the incidence and severity of the effects (dose-response assessment). 

Then the unattached fraction was calculated in each measurement and was found to be between. 05 and. 15 without aerosol sources in the room and below. 05 in the presence of aerosol sources. The effective dose equivalent was computed with the Jacobi-Eisfeld model and with the James-Birchall model and was more related to the radon concentration than to the equilibrium equivalent radon concentration. On the basis of our analysis a constant conversion factor per unit radon concentration of 5.6 (nSv/h)/(Bq/m ) or 50 (ySv/y)/(Bq/m3) was estimated. 

The fraction of unattached daughters (fp), the equilibrium factor (F) and the activity median diameter (AMD) are plotted in Figure 6 for all the measurements. The AMD is derived from the aerosol measurements. These three parameters are important in the dosimetric models. At the top of Figure 6 the effective dose equivalent is plotted, computed with two models called the J-E (Jacobi-Eisfeld) and J-B (James-Birchall) models in the NEA-report (1983, table 2.9, linear interpolation between AMD=0.1 and 0.2 ym). The figure also shows the effective dose equivalent calculated from the equilibrium equivalent radon concentrations with the NEA dose conversion factor (NEA,1983, table 2.11). 

Figure 6a. Evolution of the activity median diameter (A.M.D.), the equilibrium factor (F), the unattached fraction and the effective dose equivalent (AJ-B, V J-E, + NEA) during the case studies.

Figure 9. Effective dose equivalent per hour and per unit radon concentration (A J-B, V J-E), equilibrium factor ( ) and unattached fraction (o, right ordinate) versus the attachment rate. The curves are calculated as in Figure 7.

Effective dose equivalent. If it is assumed that the weighting factor for bronchial dose equivalent is 0.06, the unattached fraction of potential alpha-energy in room air is typically about 570, and that the aerosol AMD is typically 0.12 pm (Reineking et al., 1985), the... 

In spite of the complexity of dealing with atmospheres containing multiple toxicants, considerable progress has been made in understanding some of the effects from studies using rodents. For example, it is fairly well agreed that carbon monoxide and hydrogen cyanide appear to be additive when expressed as fractional doses required to cause an effect (21,22). Thus, as a reasonable approximation, the fraction of an effective dose of CO can be added to that of HCN and the time at which the sum becomes unity (100%) can be used to estimate the presence of a hazardous condition. 

Table II. Summation of Fractional Effective (Lethal) Doses for 30-Minute Exposure of Rats to Mixtures of CO and HQ...

Fractionation of radiation therapy effects dose. Conventional fractionation consists of five 2 Gy fractions per week, which allows up to 70 Gy to be delivered to a limited mediastinal volume. Pignon et al. performed a meta-analysis, and included 13 randomized trials (24). The fractionation dose varied between 2 and 4 Gy. The analysis revealed that as the fraction got larger the toxicities increased (24). 

Other factors that determine the absorbed fraction of inhaled glucocorticoids include the age of the child, as lung deposition of inhaled drugs increases with age (80). Therefore, the minimum effective dose may fall as the child becomes older. Moreover, it is reasonable to hypothesize that systemic absorption will increase once asthma control is established (81). Furthermore, patient adherence and inhaler technique are two factors that can have a large influence on the amount of glucocorticoid inhaled and absorbed. 

The W used in calculating the effective dose is proportional to the total detriment given in Table 3.2 and, thus, takes into account fatal cancers and severe hereditary effects, weighted nonfatal cancers, and the relative severity of all fatal responses. When the whole body is irradiated uniformly, the value of wT for a particular organ is the fraction of the total detriment resulting from irradiation of that organ. Thus, the effective dose is intended to be proportional to total... 

Another factor is that the mouse may have an active repair system in the testes. Hie nonlinear response and dose-fractionation effect offer seme evidence of this,383 but other explanations are possible. There is direct evidence that the chemical reaches the testes. This kind of information is available on a large scale only for ENU, and information on other chemicals is needed. Although these studies suggest that similar phenomena apply in man, this remains uncertain. 

It has to be emphasized that this expression is only applicable to compounds that are absorbed by diffusion and do not suffer a first-pass effect. The compounds that are actively absorbed (at least in part) along the enterocyte membrane, as well as those that are actively and substantially excreted to luminal fluid from the membrane or even the cytoplasm of the absorbing cells (i.e. P-gp substrates), should not be used for such approaches. For the compounds tested, the fraction of dose absorbed in vivo coincides with oral bioavailability (/ ), since they are passively absorbed and do not suffer first-pass metabolism. 

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