Effective dose from experimental work

It should be emphasized that this kind of comparison is quite theoretical, and it does not provide absolute unsafe exposures, nor does it specify safe levels. However, with the present understanding of the animal experiments it would appear prudent to lower the TLV values for the compounds for which the human exposure may be up to 1/100 of the effective human dose. Even though the extrapolation from animal tests is compounded by uncertainties, the revision of the hygienic standards concerning the pregnant worker appears justifiable in such cases. With ever-increasing female participation in the work force, more emphasis should be placed on reproductive hazards and their prediction, in the absence of adequate epidemiologic data, from experimental results. 

Cardiac effects were reported from early experimental work using very high doses of ebastine, but they are not believed to be clinically relevant in normal use. In one study serial electrocardiograms showed no changes with doses up to the maximum used (30 mg). Ebastine in doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval in healthy subjects (2). Co-administration of ebastine with ketoconazole or erythromycin did not lead to significant changes in the QTc interval (3,4). 

Many of the questions which are being tackled in studies of children can also be investigated in studies of animals. Information on dose-response relationships, the persistence or reversibility of effects, and periods of critical exposure can be obtained from animal work. Animal studies are of value because they are experimental in design, and therefore the exposure of the animal to lead and the time course of the exposure can be experimentally manipulated. A further major advantage is that they allow differentiation between biological and behavioural effects. 

Steinhausler (1987) and Martell (1987) review the dosimetric models and related model studies. Their view is that there are still very large uncertainties in the existing data and in the extrapolation from the exposure and response data for underground miners and experimental animals to the health effects of the radon progeny levels to which the general public is exposed. B.L. Cohen (1987) describes his work to relate radon measurements with lung cancer rates for various geographical areas to test the concept of a dose threshold. 

The second example considered the absorption of soluble insulin from subcutus. The problem here was to establish a set of consistent hypotheses that could explain the observed volume and concentration effects. At the time when the model was formulated there was no notion of the possible role of polymerization in the absorption process for insulin. Most experiments were performed at normal pharmacological concentrations (40 IU/ml) and injection volumes (0.3 ml), and the work was oriented towards elucidating the importance of exercise and skin temperature at the absorption site. Such experiments are obviously important, since variations in skin temperature may pose a problem in the control of labile type I diabetes. Analyses of a single set of data, obtained partly at micro-dose levels, allowed us to identify processes in the skin that were not amenable to direct experimentation. 

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