Product toxicity concerns

Isqacs P.A., Elastomer alloys in medical products reduce costs and toxicity concern, Elastomerics, 121, 26, 1989. 

For some important insect pests there are still no satisfactory chemical controls. Such problems should be given due consideration in the development program. Many of these problems appeared to be solved with the discovery of DDT, benzene hexachlo-ride (hexachlorocyclohexane), and some of the more recent insecticides. Further studies of the toxicity of some of these products to warm-blooded animals have raised the important question of the advisability of continuing their use where food and feed products are concerned. Considerable attention is being centered on finding safer analogs, such as TDE and methoxychlor, and new and better insecticides. 

Fires starting in a room may eventually get transferred to a plenum above it. However, by the time the effects of such a fire cause PVC products (rigid conduit, ENMT conduit and wire coating) in the plenum to burn, the room has already reached flashover conditions. Furthermore, the smoke generated by the room fire fuel causes much faster toxic concern than that from the PVC products in the plenum. 

The sponsor should consider evaluating forced degradation products in animal studies to determine if they present a toxicity issue, and, if so, an appropriate limit to ensure safety. Failure to identify toxic degradation products early in the development program can be costly mistake if the drug has to be abandoned later because of potential toxicity concerns. 

Com is one of the most heavily herbicide-reliant crops, and intense weed pressure results in the use of a number of pre-emergent and post-emergent products. Regulatory concerns have foeused largely on potential groundwater and surface water quality impacts, although concerns with worker exposure and chronic toxicity of some herbicides have also arisen. 

Long-life by-prodncts of the flnorocarbon synthesis by electrochemical fluori-nation are the perflnorooctansnlfonic acid and their corresponding salts (perflnorooctyl sulfonate, PFOS). These environmentally critical products (with concerns abont persistence, bioaccnmnlation and potential toxicity) are avoided by synthesis via telomerisation. 

Chlorambucil is noncombustible, but toxic, corrosive, or flammable thermal decomposition products such as carbon monoxide, hydrogen chloride, and oxides of nitrogen may form if involved in a fire. Because of possible aquatic toxicity concerns. 

The concept of immobilized ionic liquids entrapped, for instance, on the surface and pores of various porous solid materials (supported ionic liquid phase, SILP) is rapidly become an attractive alternative. In addition, the SILPs can also answer other important issues, such as the difficult procedures for product purification or IL recycling, some toxicity concerns and the problems for application in fixed-bed reactors, which should be addressed for future industrial scale-up. This new class of advanced materials shares the properties of true ILs and the advantages of a solid support, in some cases with an enhanced performance for the solid material. Nevertheless, a central question for the further development of this class of materials is to understand how much the microenvironment provided by the functional surfaces is similar or not to that imparted by ILs. Recent studies carried out using the fluorescence of pyrene to evaluate the polarities of a series of SILPs based on polymeric polystyrene networks reveal an increase in polarity of polymers, whereas the polymer functional surfaces essentially maintain the same polarity as the bulk ILs. However, this is surely not a simple task, in particular if we consider that the basic knowledge of pure ILs is still in its infancy, and we are just starting to understand the fundamentals of pure ILs when used as solvents. 

There are a limited number of regulatory approved antimicrobial preservatives which can be used in ophthalmic products, and some of these are becoming less favoured because of increasing awareness of ocular toxicity concerns. Therefore, it can be a challenging exercise for the formulator to find a preservative to use with the following attributes ... 

Metal Free Transition metal catalysts are highly effective for C—H bond activation. However, transition metal complexes are not only expensive, but also difficult to remove from the reaction products, resulting in toxicity concerns. DDQ is a well-known oxidant in organic chemistry [33]. For many years, it has been used for the oxidation of alcohols to ketones and aromatization. The first intermolecular C—C bond formation was realized by DDQ-mediated Mukaiyama-type aldol reactions [34], The reactions of electron-rich benzyl ethers and silyl enol ethers afforded 3-alkoxy-3-phenylpropionyl derivatives at ambient temperature with moderate to excellent yields (Equation 11.12). 

The first-generation of PKC inhibitors include staurosporine, a natural product originally isolated in 1977 from bacterium Streptomyces staurosporeus. Staurosporine was the first of over 50 alkaloids to be isolated with this type of bis-indole core structure. However, staurosporine inhibits PKC isoforms non-selectively, and this lack of specificity precludes its clinical use due to toxicity concerns. Nevertheless, staurosporine has become a valuable research tool to induce apoptosis. In addition, staurosporine serves as a versatile starting material for the synthesis of novel semisynthetic analogs. 

For some solvents, recent legislation in the USA, and proposed legislation in Europe, sets a maximum residual limit for processing chemicals in finished pharmaceutical products. The criteria are based on toxicity concerns ten solvents are present in the European Pharmacopoeia issued in July 1995, including methylene chloride, acetonitrile and secondary butanol. While their use is not precluded, greater care is now required to ensure compliance with the rules. This may involve more intensive and expensive recrystallisation procedures to remove trace amounts of solvent when they are used in the latter stages of the manufacturing process. 

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