Dose-response curve linear

Eor compounds with presumed linear dose-response curves, such as genotoxic and carcinogenic compounds for which it is assumed that a no-effect level does not exist and for which the mechanism of action may be regarded as similar, response addition and dose addition will provide identical results (Konemann and Pieters 1996). 

Fig. 3. The way in which an envelope of additivity may be calculated for two pairs of cytotoxic agents (A + B and C + D) where one of each pair gives a non-linear dose-response curve (isobologram analysis from Peckham and Steele ref. 27).

The ICSs beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide that are currently available for use are compared and listed in Table 26-12. The ICSs have pharmacokinetic differences that result in different topical/ systemic activity. Most evidence is consistent with log-linear dose-response curves for both indirect and direct responses. The log-linear nature of the dose-response curve for corticosteroid activity raises the issue of how much of a difference in dose (or lung delivery) or potency is detectable. The dose-response curves for the ICSs are relatively flat primarily because all the measures used to assess efficacy (lung function, BHR, symptoms, and as-needed short-acting inhaled /32-agonist use) are downstream events from the anti-inflammatory activity. In general, it takes a fourfold difference in potency or dose to detect clinically significant differences. The table of comparative doses (see Table 26-12) is based on extensive comparative clinical trials. Clinical comparative doses take into consideration potency differences as well as lung delivery differences from the various devices. 

Figure 24.1. Estimated hypothetical cancer risks from chemical exposures by way of a linear dose response curve. [Adapted from 3-1 of EPA (1996).]...

So if outright bans are problematic, what is it about the linear dose-response curve that makes it a preferred approach for cancer prevention ... 

Figure 2 Linear and Non-Linear Dose-Response Curves...

H) side chains are replaced by the pseudoisosteric Cys" —Cys bridging side chain (-CH2-S-S-CH2-) group. [Cys", Cys ]-a-MSH was found to have superpotency in the frog skin assay system, being about 10-100 times more potent than the native hormone in this system over the linear portion of the dose-response curve. In addition, the peptide som etimes exhibits activity at concentrations as low as lO" " M (about 1000 times the minimum effective dose potency of a-MSH), but linear dose-response curves cannot be obtained. The reasons for this are unclear, but may reflect variability with season and from animal to animal, and perhaps variability in compartmentalization, receptor sensitivity, and/or non-specific adsorption properties of the cyclic peptides. 

The shape of the survival curves differs considerably. Whereas for photon irradiation the typically shouldered shape is observed, low energy carbon irradiation leads to an approximately linear dose response curve. 

Figure 3.2. Sample Linearized Dose-Response Curves for Threshold and Nonthreshold Responses...

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