General toxicity screens

Predictions of no, or low, toxicity in a general drug screening approach should be used to indicate a possible absence of toxicity in potential drug candidates. Inevitably this would require further toxicological assessment of potential drugs to ensure safety. 

Screening Techniques for Detecting Toxicity. Simple toxicity screening techniques are necessary to identify toxic species and to monitor the efficacy of isolation and purification procedures used to purify toxins. Atterwill and Steele 108) have recently comprehensively reviewed in vitro methods for toxicology and so much of the following is in the nature of a general overview. 

Other types of reproductive toxicity studies, e.g., the prenatal developmental toxicity study, the reproduction/developmental toxicity screening study, and the developmental neurotoxicity study (Section 4.10.3) may give some indications of general toxicological effects arising from repeated exposure over a relatively limited period of the animal s life span as clinical signs of toxicity and... 

Marquet, P., N. Venisse, E. Lacassie, et al. 2000. In-source CID mass spectral libraries for the general unknown screening of drugs and toxicants. Analusis 28 925-934. 

The toxic effects observed with intact animals has its counterpart in the cytotoxic effect, which has been recorded for nearly 180 alkaloids (Table III). These data have been obtained by screening many natural products for anticancer activity. However, an alkaloid that can kill a cancer cell is usually also toxic for normal cells. Therefore, the data shown in Table III are another indication of the general toxicity of alkaloids toward animals. Because this toxicity applies also for herbivores, the production of alkaloids by plants can certainly be interpreted as a potent antiherbivore mechanism. 

Marquet, P., Saint-Marcoux, F., Gamble, T.N., Leblanc, J.C. (2003). Comparison of a preliminary procedure for the general unknown screening of drugs and toxic compounds using a quadrupole-linear ion-trap mass spectrometer with a liquid chromatography-mass spectrometry reference technique. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 789(1) 9-18. 

Assessments of motor function are often included in the neuropsychological test batteries utilized in occupational exposure studies. Typically, these tend to be relatively simple measures of motor capabilities, probably for two reasons. The first is that the inclusion of vigilance tasks such as those described previously depends on motor coordination in addition to sensory capabilities therefore, toxicant-induced changes in such performances may already be indicative of motor impairment. This can then be pursued by inclusion of some additional and more direct assessments of motor function in the battery. The second reason relates to logistical reasons and practicalities. Test batteries such as the WHO Neurobehavioral Core Test Battery and the NFS are typically taken to the site where measurements of subjects are to be made. Thus, portability is a major consideration, and more complex assessments of motor function would incur greater equipment needs. Since the purpose of these batteries is generally to screen for adverse effects, studies providing more precise delineations of affected functions can be pursued at a later time. 

If considered desirable, a minimum screen (e.g., genotoxic potential) should be conducted. A study to detect point mutations and one to detect chromosomal aberrations, both in vitro, are considered an appropriate minimum screen. If general toxicity studies are desirable, one or more studies should be designed to allow comparison of unqualified and qualified materials. The study duration should be based on available relevant information and performed in the species... 

Recently, LC-MS techniques have become increasingly popular as an approach to analytical problems. In keeping with this development, Saint-Marcoux et al described a general unknown screening procedure for serum samples, using SPE and subsequent liquid chromatography-electrospray mass spectrometry (LC-ESIMS). This method allows for the detection and identification of pesticides and also other drugs and toxic compounds. 

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