Toxicity aspects

Use in general toxicity testing and reproduction, teratological and behavioral toxicity (aspects of public acceptance as a species for testing)... 

Ciaccio El. Mercury therapeutic and toxic aspects. Semin Drug Treat 1971 l(2) 177-94. 

In the foregoing sections, pharmacon metabolism has been considered in relation to the pharmacodynamic, especially toxic aspects of action. Drug distribution also plays a role in the pharmacodynamic phase of drug action. Modulation of drug distribution, for instance, exclusion of penetration of particular barriers in the organism (e.g. the blood-brain barrier), or preferential bioactivation or bioinactivation in particular tissues, can modulate the spectrum of action of compounds and possibly exclude particular undesired effects. 

The EC funded HAIR project (http //www.rivm.nl/stoffen-risico/NL/hair.htm) is devoted to integrating the different methods for the assessment of pesticides into a combined index. The intention is to go beyond the environmental and ecotoxicological properties of pesticides and to address the human toxicity aspects as well. The ultimate target is to produce an index useful to regulators changed with evaluating the EU policy on pesticides and to reduce the overall impact of the pesticides. This project also considers other chemicals besides pesticides. As in many other examples, the lessons learned from pesticides... 

Toxicity aspects related to use of benzene were avoided... 

Comparison between foodstuffs and pharmaceuticals based on simulated extractive tests is inevitably difficult, because the site and mode of absorption may vary, because of the difference in the pre-storage period and the frequency of use, and the volume/weight of the product taken. With foodstuffs, the contact period between product and pack is usually shorter, but the quantity taken and frequency of use are greater, e.g. daily intake of margarine. Thus any EU extractive procedure may provide useful additional information for the pharmaceutical industry as part of stage 1 involving the screening of the material, but the simulants used may bear little relationship to the final pharmaceutical form. These tests are also more relevant to toxicity aspects rather than to irritancy. For food extractive tests see Appendix 8.6. 

An important aspect in all drug delivery is the toxicity of the drug as well as that of the drug carrier. Therefore, toxicity has to be assessed also for microemulsion formulations. In microemulsion systems, the main concern regarding toxicity has to do with the cosurfactants used. For example, the majority of the work on the pharmaceutical application of microemulsions has involved the use of short- or medium-chain alcohols, e.g., butanol. In a range of studies it has been shown that these cause toxic side effects. For example, inhalation studies of the toxicity of 1-butanol, 2-butanol, and / -butanol in rats showed a dose-dependent reduction in fetal weight [56]. Furthermore, aqueous solutions of ethanol, propanol, and butanol were shown to result in elongated mitochondria in hepatocytes after 1 month of exposure [57]. (In addition to the toxicity aspects of these alcohols, microemulsions formed in their presence are often destabilized on dilution of the continuous phase.) Furthermore, many studies so far have involved aliphatic or aromatic oils, such as hexane or benzene, which obviously are unsuitable for pharmaceutical use. Moreover, ionic surfactants could in themselves be toxic and irritant [58]. 

Studies have been carried out on a number of animals, particularly species of crab, lobster and zooplankton, and on the in vivo metabolism of a wide range of xenobiotics. Cytochrome P-450 and the MFO system, and to a lesser extent glutathione S-transferase, have been characterized most. Much less is known of other enzymes and of mechanisms of xenobiotic activation and toxicity. Aspects reviewed include cytochrome P-450 monooxygenases (Bend et al. 1981 James 1989b), and petroleum hydrocarbon metabolism in marine plankton (Corner 1978). 

A relatively large amount of unfavourable publicity has appeared in the media related to their flammability, smoke and toxicity aspects. Examples are the major fire in 1992 at a vegetable processing facility in Yuma (Arizona, USA), in 1996 at the international observatory in Hawaii, in 2002 in nightclubs in Chicago, Rhode Island and Bali. Producers of polymer foams have made determined efforts to demonstrate that these products do not present an unacceptable fire hazard when properly installed and maintained [153,154]. 

K. Mojsiewicz-Piehkowska, Safety and toxicity aspects of polysiloxanes (sihcones) appHca-tion, in A. Tiwari, and M. Soucek, eds.. Concise Encyclopedia of High Performance Silicones, Wiley-Scrivener Publishing, 243-251,2014. 

Besides the risks for health and equipment, the question of environmental compatibility of the disposal of lithium batteries after use and of scrap of the production has to be answered. The entire chemical, thermal, electric, and toxic aspects of the lithium battery technology have to be considered. The lithium metal is far less harmful than the heavy metal mercury. On the other hand thermal decomposition of a lithium high rate battery might be locally much more disastrous than a bursting alkali manganese or lead-acid battery. 

The results of the analysis regarding the economic, environmental, and toxic aspects, among others, show that this technology is the environmentally cleanest method of lipid extraction. It is not seriously affected by the economic market fluctuations, which is a positive factor when considering other methods... 

Safety and Toxicity Aspects of Polysiloxanes (Silicones) Applications 245... 

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