Threshold-like Dose-response Relationships in a Modified Linear-no-threshold Model: Application of Experimental Data and Risk Evaluation

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Precise evaluation of dose-response relationships at low doses is essential for proper risk assessment. It is commonly found that responses of more than background are not observed at very low doses, and the responses increase with dose increments to a maximum at high doses. Here, a variety of dose-response curves for a modified linear-no-threshold model were demonstrated with ordinary and logarithmic graphs. In general, the dose response was observed to be linear when repair or detoxification capacity was far smaller than the background response level, while “threshold-like” dose responses were observed when the capacity was large enough. However, linear increase in mutation frequency was still observed even below the “threshold-like” doses albeit a response per dose was very low. Mutagenicity data of N-methyl-N′-nitro-N-nitrosoguanidine and sodium azide to Salmonella typhimurium, reported by Sofuni et al. (Environ Mutagen Res. 2005; 27: 61), were applied to the model, as an example of estimation of various parameters and of evaluation of the mutation risk at low doses. Risk estimation from experimental data is discussed.<br>

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