Effective dose method

The best precision (lowest RSD) occurs at the steepest point on the curves. The difference between these points (unknown minus standard) is the effective dose (ED)  

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Gangoli, S. (ed.) (1999) The Dictionary of Substances and their Effects (DOSE), Royal Society of Chemistry, London. Gibbons, R. (1994) Statistical Methods for Groundwater Monitoring, Wiley. 

Indoor air radon concentrations measured in a randomly selected sample of 220 Irish houses have been found to range from about 20 Bq/nr to as high as 1740 Bq/nr with a median value of 61 Bq/nr. Using current dose estimation methods the estimated effective dose equivalents due to radon daughter inhalation in these houses are 1.6 mSv/year (median value) and 46 mSv/year (maximum value). 

By the Method of Frequency the stimulus range is selected in discrete intervals so that the frequency of positive answers is distributed over the range between 1% and 99%. In general, the frequency of positive responses either for an individual or for a group, is cumulatively normally distributed over a geometric intensity continuum. The absolute odor threshold can then be defined as the effective dose corresponding to an arbitrarily selected frequency of positive responses, ordinarily 50% ED50 Effective dose at the 50% level. 

Without the availability of animal dafa, how would one decide on the first dose of a molecule (that has never been administered to any animal) to be given to man A frequently used method is to give a volxmteer 10% of the lowest no-effect" dose seen in two or three animal species. How would one decide on the route of administration Some compounds are very toxic to intact veins. How could one give reasonable assurance of safety of a new chemical never before administered to a human The only viable option is to determine tolerance in the veins of lower animals before moving to a volxmteer. Should animal activists not have to put forth their actual protocol for studying a new drug candidate in humans How would they answer the questions raised above ... 

Pereira (1994) provided further evidence of the effect of dosing method (gavage versus drinking water) and vehicle (com oil versus water) on hepatic cell proliferation in female B6C3Fi mice. Animals received either 263 mg/kg/day chloroform by gavage in com oil or 1,800 ppm chloroform in drinking water,... 

We designed our studies to establish potency, onset and duration of physiological and cognitive effects, dose/response relationships, and methods of treatment. For compounds of greatest interest, we measured the relative effectiveness by various routes of administration. 

Both independent studies and internal industry research highlight the relevance of prodnct differences in determining nicotine dosing. Historical differences are indicated, as are differences among brands. The evidence demonstrates the effectiveness of methods adopted by mannfactnrers to control nicotine dosing and target the needs of specific popnlations of smokers throngh commercial product development. 

A number of substituted bisindole oxazolidinedione derivatives were prepared using the methods described above (Table VI) (79-81). When examined for their ability to induce a mitotic block in CHO cells, these compounds were active from 2 to 0.002 p.g/ml (Table VII), and compounds having the greatest degree of potency in this in vitro system were evaluated in several experimental tumor systems (Table VIII). The in vitro potency of these compounds appears to correlate with their in vivo potency as reflected by the minimum effective dose that could be administered without toxicity. Several of these compounds were evaluated for their antitumor efficacy when administered by the oral route (Table IX). Compounds 96 and 107 were shown to be exceptionally active in this regard. 

One difficulty in using this approach is to determine when a specific Cl actually deviates from 1 (additivity), as the method of isoboles as developed does not include measures to decide whether deviations from the line of additivity are systematic or simply due to chance or experimental error (Cassee et al. 1998). One way of dealing with this problem is to calculate confidence intervals for the iso-effective doses of the single compounds and to add a confidence belt to the line of additivity (Kortenkamp and Altenburger 1998). This envelope of additivity is an area in which those combinations of two compounds are lying that has a specific effect and may reasonably be considered as showing no interaction (for details see Cassee et al. 1998). 

Selected entries from Methods in Enzymology [vol, page(s)] Median effective dose, 235, 29, 31, 33 determination of median infectious dose, 235, 29-39 median lethal dose, 235, 29 moving average interpolation, 235, 32-34, 36-37, 39 probit analysis, 235, 31-36, 39 Reed-Muench method, 235, 30, 33-35 staircase method, 235, 33, 37-39 median response, 235, 29 dose range for animal experiments, 235, 29 50% end-point determination, 235, 29-30. 

A new additive dose method is proposed to obtain the age directly without extrapolating the growth curve.1115 The experimental growth curve at the artificial irradiation dose rate gives simply the defect production efficiency (G-value) from the initial growth and the interaction distance, d, between spins from the saturation behaviour. The latter involves the effect of magnetic dipolar and exchange interactions of similar and dissimilar spins and also destabilization of a spin in a distorted area by a local lattice distortion. 

The intensive search for new organic fungicides has continued for over 30 years. The technique employed in most laboratories is to make an extensive survey of various structures by empirical methods to locate materials that suppress spore germination on glass slides or prevent mycelial growth on nutrient agar plates or rolled tubes. Those materials having an ED ] (effective dose for 50% inhibition) in (he order of 10 ppm are further tested in use applications. 

We now present IETS data for dimethyldimethoxysilane (DMDMS), and dimethyldiethoxysilane (DMDES) liquid dosed onto thermal and plasma alumina, and for dimethylvinylethoxysilane (DMVES) applied to plasma alumina with a slightly different liquid dosing method. These results illustrate the effect of different dosing methods, and substrate-dependent adsorption effects. 

For clinical practice, the lowest effective dose should be achieved, and all children using inhaled glucocorticoids should have their growth measured every 6 months, as this is a sensitive method of detecting significant systemic effects (84,140). 

For noncarcinogenic hazardous chemicals, NCRP believes that the threshold for deterministic effects in humans should be estimated using EPA s benchmark dose method, which is increasingly being used to establish allowable doses of noncarcinogens. A benchmark dose is a dose that corresponds to a specified level of effects in a study population (e.g., an increase in the number of effects of 10 percent) it is estimated by statistical fitting of a dose-response model to the dose-response data. A lower confidence limit of the benchmark dose (e.g., the lower 95 percent confidence limit of the dose that corresponds to a 10 percent increase in number of effects) then is used as a point of departure in establishing allowable doses. 

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