Dose-ranging programme

By the end of a dose-ranging programme of studies, the sponsor should be able to define the... 

Concentration of the antigen can be readily determined from a standard dose-response curve. The range of antigen concentration rarely exceeds two logic dilutions and is, therefore, much smaller than for different antisera. Microcomputers or desk-top programmable calculators, interfaced with microplate readers, may help to linearize rapidly the dose-response curves and to transform the values obtained for the test-samples into concentrations. In contrast, dose-response curves for antibodies are complicated by a variety of factors ... 

The BMD approach has been put forward as an alternative to the no-observed-adverse-effect level (NOAEL) and lowest-observed-adverse-effect level (LOAEL) approach for health effects because it provides a more quantitative alternative point of departure for the first step in the dose-response assessment (International Programme on Chemical Safety, in press). The BMD approach is based on a mathematical model being fitted to the experimental data within the observable range and estimates the dose that causes a low but measurable response (the benchmark response) typically chosen at a 5% or 10% incidence above the control. The BMD lower limit (BMDL) refers to the corresponding lower limit of a one-sided 95% confidence interval on the BMD. Using the lower bound takes into account the uncertainty inherent in a given study and assures (with 95% confidence) that the chosen benchmark response is not exceeded. 

The success of the Stellite reduction programme can be judged by comparing the figures given in Table i. The personnel doses on the KONVOI plants are in the range 100-300 man-mSv, whereas on the Stellited plant doses are from five to ten times higher. 

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