And unintended effects

The results of all relevant nonclinical pharmacology, toxicology, pharmacokinetic, and investigational product metabolism studies should be provided in summary form. This summary should address the methodology used, the results, and a discussion of the relevance of the findings to the investigated therapeutic and the possible unfavorable and unintended effects in humans. 

For many in the chemical industry these claims may sound hollow. Everyone knows that global expansion of the chemical industry, even with good faith efforts to comply with safety and pollution requirements, is assumed to carry with it adverse and unintended effects from chemical production and use. Such is the price of economic growth - correct Wrong. In fact, our passive acceptance of this paradigmatic view of the chemical industry may pose the most formidable obstacle to change. If so, the challenge may be more in our minds than our capabilities. 

A tool intended for use by a range of personnel should be easily and rapidly employed and its results should be repeatable and auditable. These criteria suggest that its operation should be mechanistic and based on rules. Yet, the management issues to be analysed by the intended method can have subtle, unexpected and unintended effects, which suggests that their successful exploration requires a creative approach. The method s design must therefore provide procedure-based operation, in which the procedures demand, in appropriate places, creativity. This needs to be designed for. 

Abstract The chapter describes current procedures for the safety assessment of genetically modified crops and foods. The concepts of substantial equivalence, the conventional comparator, and intended and unintended effects are introduced. Most published examples of substantial equivalence testing deal with crops that have been modified for insect resistance or herbicide tolerance. A standard procedure has developed based on broadly similar field trial designs, sampling schemes and targeted analyses of a consensus set of compounds for each crop. The main characteristics of the procedure are summarised with reference to published analyses of this type of crop and different statistical approaches to judging equivalence are discussed. 

Unintended Effects represent a statistically significant difference in the phenotype, response or composition of the GM plant compared with the parent from which it is derived, but taking the expected effects of the target gene into account. Such comparisons should be made when GM and non-GM plants are grown under the same regimes and environments. Definitions of intended and unintended effects are from Cellini et al. (2004). 

Compound optimization, to screen a series of therapeutic diug candidates to find the compounds that are most specific for the target protein and those that cause unintended effects, i.e. improved understanding of the molecular mode of action including structure-activity relationships for on-target versus off-target effects... 

The disinfection of drinking water has been rightly hailed as a public health triumph of the twentieth century. Before its widespread use, millions of people died from waterborne diseases. Now, people in developed nations receive quality drinking water every day from their public water systems. However, chemical disinfection has also produced an unintended health hazard the potential for cancer and reproductive and developmental effects (including early-term miscarriages and birth defects) that are associated with chemical disinfection by-products (DBFs) [1-6]. Research is being conducted worldwide to solve these important human health issues. 

The medicinal chemistry and pharmacology of codeine can also shed light on why specific side effects (the unintended, undesirable, and unwanted effects) associated with codeine occur. Codeine s side effects, or toxicities, are discussed in the next chapter. 

But let me also be quick to point out that the impacts will not be as significant as they at first appear. Hie number of new chemicals is not a complete measure of the output of chemi-cal innovation. It ignores qualitative factors about the chemicals, a very important one of which is the unintended environmental and health effects resulting from the use of the product. 

The introduction of foreign DNA leads to many unintended and unexpected effects (Rist 2000). 

Maciel (117) described the formation of the trityl cation 16 on silica-alumina in a 1984 symposium in retrospect it is surprising that no one followed up on this work until much later. 16 easily forms from triphenylcar-binol and other precursors in solutions of modest acid strength. The early observation of such an easy cation had the unintended effect of suggesting that real carbenium ions would not so easily be detected in NMR studies of solid acids. Over a decade elapsed before we characterized the rert-butyl cation on A1C13 powder (43). 

Of course, also the set of relevant alternatives has to be defined. If too many alternatives exist, a checklist approach might be used to arrive at a shortlist or a dominance analysis can be performed based on the performance matrix of the alternatives. In case of a lack of alternatives various techniques can be explored to generate additional alternatives (cf. Keeney 1992, pp. 198-240). The alternatives to be analyzed in detail should be described carefully because the way they are described can have unintended effects on decision makers preference statements. The examples provided by Tversky and Kahneman (1986) illustrate this point. 

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