Other examples of alternating toxicities

Only a few ahphatic fluoro-nitro compounds have been examined, and if n is odd the material is toxic. Having regard, however, to the known relaxation of smooth muscle, irrespec tive of the type of innervation, by the nitrite ion, the writer feels that caution is required in drawing conclusions regarding the toxic action of fluoro-nitro compounds. 

123 we described the preparation of 2 fluoroethyl thio-cyanate by the reaction 

50 for mice of this compound was 15 mg./kg. Some of the higher members of this series show an alternation of toxicity, as do also the mercaptans produced by reduction of the thiocyanates by hthium aluminium hydride. Thus F(CH2) SH was toxic when n was even. 

123 an account was given of our preparation of 2-fluorosulphonyl chloride by the reaction 

Although not containing fluorine, certain acids examined by Wain also showed an interesting alternation of biological activity. When the growth-regulating activity of compounds of 

However, it has recently been shown that when the substituents in the benzene ring of the phenoxy acid are changed, then alternation in activity is exhibited in the wheat-cylinder test, whereas in the pea curvature and leaf epinasty tests, only the first member of the series was active. This means that the / -oxidizing system present in pea and tomato tissue is incapable of degrading the side chain of these particular substituted phenoxy acids. This approach opens up the possibility of selectively controlling weeds in a wide range of crops. 

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Hexavalent chromium is a known human carcinogen, however, and its commercial use is strictly regulated and highly discouraged by environmental authorities. An alternative metal to chromium in premetallized azo dyes would have to have the same color and fastness properties as chromium but without the toxicity. It has been found that iron, which is essentially nontoxic, often imparts the same desirable qualities as chromium when used in azo dyes [82,83]. This is exemplified in comparing azo dyes 44 and 45. Dyestuff 45 has the same color and fastness as 44, but does not contain chromium. Other examples of dyestuffs that use iron rather than chromium are available [82, 83]. 

Recently, there has been a growth of interest in the development of in vitro methods for measuring toxic effects of chemicals on the central nervous system. One approach has been to conduct electrophysiological measurements on slices of the hippocampus and other brain tissues (Noraberg 2004, Kohling et al. 2005). An example of this approach is the extracellular recording of evoked potentials from neocortical slices of rodents and humans (Kohling et al. 2005). This method, which employs a three-dimensional microelectrode array, can demonstrate a loss of evoked potential after treatment of brain tissue with the neurotoxin trimethyltin. Apart from the potential of in vitro methods such as this as biomarkers, there is considerable interest in the use of them as alternative methods in the risk assessment of chemicals, a point that will be returned to in Section 16.8. 

Probably the most fundamental problem facing the development of greener products and processes is the measurement of progress and the development of appropriate methods for comparison of alternatives. In many instances it will be obvious that improvements have been made, for example when a toxic material is replaced by a non-toxic alternative, keeping all other process conditions essentially the same, or when the energy requirement of a process is reduced. 

There is an evolving variety of alternative healthcare practices and products to choose from. (See Terminology sidebar.) Adults and adolescents alike are asking themselves questions such as, Should I take a pill for my headache, or drink chamomile herbal tea There are several scientific counterparts to this seemingly simple question, for example Are these both remedies Are they equally effective Is one healthier or less toxic than the other Can they be used together At this time, there is no comparative information on codeine versus alternative medicine (e.g., acupuncture) as effective treatments for pain, cough, and diarrhea. 

Seeing chemicals as things that are used for particular purposes opens up the question of whether there are alternative, less risky means of fillfilling those purposes other chemicals or other methods. For example, one can keep dust mites out of duvets by impregnating the cover with a chemical toxic to dust mites or by using a very finely woven material, which in itself presents no risks to human health. If we are at all uncertain about the effects of the toxic chemical, the second method is a great deal less risky than the first. We should therefore substitute the use of the chemical by the use of finely woven material, even if we cannot identify the risks of the chemical to organisms other than dust mites. 

Here, the important aspect is that the QSAR models, from different sources, and also those developed within CAESAR, for instance, will be integrated, evaluating their possible use. Indeed, the final target of the registration is the overall information about the acceptability or otherwise of the chemical substance. It may happen that for a certain compound, the toxicity is not so critical because the exposure scenario reduces the concern, for instance. Thus, QSAR is only one component of a more complex strategy for the evaluation of the chemical substances. Multiple factors have to be considered, and also data from different sources. OSIRIS will be important because it will organize these multiple sources into a combined scheme, and thus provide practical examples of the use of QSAR. It is also important to notice that this means that the QSAR methods are tools that are suitable for integration with other approaches, not necessarily alternative, but supplementary tools. 

In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, through the use of alternative methods, for example, in vitro methods or qualitative or quantitative structure-activity relationship models or from information from structurally related substances (grouping or read-across). 

In the case of green chemistry, and more especially chemical substitution, a number of policy instruments are relevant. The traditional approach is to ban certain toxic chemicals in order to induce substitution efforts. Such bans are usually preceded by examples of successful substitutions, as it is controversial to ban chemicals when no alternatives exist at reasonable cost. Otherwise, industry is often granted generous phase-in periods, in order to develop substitutes. A third way is to grant derogations when it is hard or very costly to develop substitutes. The latter approach has been applied in the context of the EU Restriction of Hazardous Substances (RoHS) Directive (Directive 2002/95/EC), which bans six substances in electrical and electronic products. A slightly less interventionist approach is to put restrictions on uses of certain chemicals. Other administrative approaches include the ban of chemicals, or restrictions in use, in individual operations when these apply for permits. 

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