Screening animal testing

Iversen (1991) stresses the need for some in vivo testing for neurotoxicity and emphasizes the value of sensitive behavioral tests. Behavioral tests are described for mice and rats, which provide measures of mood, posture, CNS excitation, motor coordination, sedation, exploration, responsiveness, learning, and memory function. Such assays can function as primary screens for neurotoxicity before adopting a stepwise scheme of in vitro tests to discover more about the initial site of action of neurotoxic compounds. It is argued that the requirement for animal testing can be drastically reduced by adopting structured in vitro protocols such as these. 

Results from this preliminary study suggest that a combined approach based on alternative methods could be positively applied to chemical screening in order to reduce the number of animal testing for carcinogenicity studies. 

Unnecessary animal testing can be avoided by relying on in vitro studies as the first stage acute toxicity and cytocompatibility test for injectable materials (Pearce et al., 2007). Many researchers have utilized in vitro studies to screen the cellular response to CNTs (Raja et al., 2007) and to investigate the various CNT-mammalian cell interactions such as oxidative stress (Manna et al., 2005 Shvedova et al., 2003, 2007), antiproliferative effects (Cui et al., 2005 Garibaldi et al., 2006), decreased cell adhesion (Cui et al., 2005), apoptosis (Bottini et al., 2006 Cui et al., 2005 Jia et al., 2005), and necrosis (Jia et al., 2005). A summary of these in vitro studies are presented in Table 12.1. 

Certain live animal testing has shown that certain additives may be harmful. If you headed a chemical company what would you do if one of the additives was suspected of being harmful Why is there an overlap between materials found in sun screens and those employed to help protect polymers from degradation from light ... 

The largest part of the observed variance in the pharmacological effect can, however, be explained by the change in relaxation rate upon interaction with the phospholipid. This simple method might therefore offer a suitable first screening system for selecting compounds for further animal testing for this class of compounds. 

During the first half of the century, there was virtually an exclusive reliance on animal testing as the primary model for drug discovery and development. New chemical entities were administered to rodents in the primary screen assay, and the appropriate responses were monitored for indications of therapeutic potential. Compounds meeting the appropriate potency and efficacy criteria were promoted to more diverse and sophisticated animal models to characterize their pharmacological profile. The responses that were monitored included blood pressure (hypotensives), latency to respond to painful stimuli (analgesics), attenuation of seizure propensity (antiepileptics) and other responses that were intuitively and pharmacologically valid indicators of medicinal potential or toxicity. Some of these methods were semiautomated and quite sophisticated for their time, particularly for cardiovascular indications [1]. 

It was very time-consuming to screen substances in animal tests for efficacy and to prepare lead analogues by classical synthesis. Therefore, it is not surprising that the researchers looked for alternatives. Today pharmaceutical companies apply computerized robotic systems in drug discovery. The starting point is the chemical library. This library does not contain books, but chemicals. Many companies keep small samples of all chemical compounds that they ever synthesized or extracted from the plant material. The amount of the samples is usually small and they are kept in microplates in dedicated temperature-controlled storage facilities. Chemical libraries of large pharmaceutical companies contain several million different compounds. 

Although there is currently a lot of research to replace the preclini-cal safety tests in animals with in vitro high throughput methods, so far success is limited to some metabolite and genetic toxicity screens. These methods have not been accepted yet by the regulatory authorities in the various countries as valid alternatives to animal tests. The reason is that in these screening assays too many false results are obtained to accept them as the only basis for safety assessments. 

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