Dose-response relationships overview

S.C. Smolinske, et al., Toxic effects of nonsteroidal anti-inflammatory drugs in overdose An overview of recent evidence on clinical effects and dose-response relationship. Drug Safety 5 252-274, 1990. 

Standards that are derived using SSDs for the soil ecosystem can in some cases be validated in the held. The overview by Posthuma et al. (2002) reported on some validation studies in which it was shown that the HC5 was lower than the no-effect concentration of studied ecosystems (i.e., in mesocosm or held conditions). An array of further studies has been published since that time. However, held studies are often difhcult to interpret in terms of dose-response relationships. This difficulty in interpreting held data is sometimes due to soil heterogeneity and a highly variable soil ecosystem. Nevertheless, held soils are relevant test systems and represent a more realistic environment. Although causality may be difhcult to assess, the use of pragmatic methods, derived from an expert judgment process, can improve the overall accuracy of standards. 

The quantitative dose-response assessment involves two different challenges, namely to determine the relationship between doses and the frequency of cases of cancer (i.e., potency evaluation), and to determine what statistical risk is tolerable or acceptable. This section gives a very short overview of some general aspects related to the quantitative dose-response assessment. The currently used approach by the WHO, the US-EPA, and the EU, as well as new approaches for the risk assessment of compounds that are both genotoxic and carcinogenic, are presented in Sections 6.3 and 6.4, respectively. 

Considering the epidemiological evidence of the health effects of particulate matter, the main purpose of toxicological studies was to prove the plausibility of the statistical associations, to elicit the components of particulate matter responsible for the health effects and to analyze the mechanisms of action and the dose-effect relationship. A vast body of data has accumulated during the past 10 years (for an overview see, US-EPA 2004, 2008). 

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