Choice of endpoint

All test methods adopted or under development by national or international standard organizations (e.g., OECD, ISO...) are suitable for WASTOXHAS. However, the choice of endpoints to be evaluated, among a large number now available, and their quantification methods, are directly related to criteria defining limit values. Examples of different chemical limits can be found in Lapa et al. (2002b). 

Cedergreen N, Streibig JC. 2005. Can the choice of endpoint lead to contradictory results of mixture-toxicity experiments Environ Toxicol Chem 24 1676-1683. 

The choice of endpoints used in studies of new therapies may evolve over time as knowledge is gained about the natural history of the disease or the reliability of surrogate endpoints. Endpoints used to evaluate the benefits of new drugs are provided in Table 4.1 for a number of diseases. Many diseases are associated with numerous medical conditions of consequence to the patient (for example, pain and disability resulting from rheumatoid arthritis), which may be the target for a particular new therapy. 

The choice of assessment scenario, like the assessment endpoint, is likely to be implied by the management goal and should be made in close consultation with the risk manager, to ensure it meets their needs. 

When the analysis is based on a continuous outcome there is commonly the choice of whether to use the raw outcome variable or the change from baseline as the primary endpoint. Whichever of these endpoints is chosen, the baseline value should be included as a covariate in the primary analysis. The use of change from baseline without adjusting for baseline does not generally constitute an appropriate covariate adjustment. Note that when the baseline is included as a covariate in the model, the estimated treatment effects are identical for both change from baseline and the raw outcome analysis. ... 

Finally most therapeutic specific guidelines contain recommendations that directly impact on statistical considerations, for example in terms of the definition of endpoints, the requirement for more than one primary endpoint, the definition of analysis sets and the choice of A. In a particular therapeutic setting it is self-evident that the requisite guidelines should be studied carefully in order to extract relevant information for statistical aspects of design and analysis. 

There are two types of Karl Fisher titrations volumetric and coulometric. Volumetric titration is used to determine relatively large amounts of water (1 to 100. ig) and can be performed using the single- or two-component system. Most commercially available titrators make use of the one-component titrant, which can be purchased in two strengths 2 mg of water per milliliter of titrant and the 5 mg of water per milliliter of titrant. The choice of concentration is dependent on the amount of water in the sample and any sample size limitations. In both cases, the sample is typically dissolved in a methanol solution. The iodine/SCVpyridine (imidazole) required for the reaction is titrated into the sample solution either manually or automatically. The reaction endpoint is generally detected bivoltametrically. 

A number of practical considerations affect the choice of experimental approaches to address a specific question. In general, these practical considerations tend to have a greater impact on applications to toxicology (where specific endpoints may not be measurable in all cell types) than studies of xenobiotic metabolism (where the principal requirement is enzyme activity). However, applications to toxicology should be considered when making a choice of an experimental approach as specific toxicological issues may develop from the metabolism studies or in other aspects of the safety assessment processes. 

The choice of titration protocol to determine the TA of a sample is dependent primarily on the color of the sample. The colorimetric titration uses phenolphthalein indicator solution to determine the endpoint of the titration. Phenolphthalein indicator solution turns from colorless to pink upon reaching the endpoint therefore, if the color of the sample interferes with this color change, the potentiometric titration is the best method. However, when using colorimetric titration, it is also common to titrate to an endpoint of pH 8.2, the endpoint of the phenolphthalein solution. 

Weyers, A. and Vollmer, G. (2000) Algal growth inhibition effect of the choice of growth rate or biomass as endpoint on the classification and labelling of new substances notified in the EU, Chemosphere 41 (7), 1007-1010. 

Interpretation of the SQT depends strongly on the correct choice of individual LOE, in particular COPCs sediment toxicity tests and endpoints. 

---