Toxicological Assessment

Toxicology is the science of poisons or, to be more precise, it is the study of the adverse effects ofxenobiotics on biological systems [19, 20]. Toxicology is an ever-developing science, and modern toxicologists consider cellular and molecular responses as the earliest indicators of exposure to exogenous agents. Toxicological developments are due both to theoretical expansion and technical improvements of different branches of science, notably biological sciences, chemistry, mathematics, and physics. Toxicology is a very broad science that can be classified into several branches relating to discipline, application and function.

Toxicological information about chemicals is, in many cases, still limited [21-24]. While data obtained from human experiences would be most useful in assessing the toxic effects of chemicals, human data are not always available for developing safety evaluations on chemicals and airborne contaminants. Moreover, as a result of many unfortunate human experiences, such as those with pharmaceutical agents such as diethylstilbestrol and thalidomide, or occupational and environmental contaminants such as lead and polychlorinated biphenyls (PCBs), it is now understood that the risks of chemicals, new products and technologies need to be assessed before adverse human experience occurs [25-27].

Therefore, as part ofa preventive strategy, it is critical to develop new approaches that are both informative and time-/cost-efficient in order to identify the potential hazards in the absence ofwidespread human exposures [19]. In general, no single method can cover the complexity of general toxicity in humans [28]. However, toxicity data can be obtained from several sources, including in-vivo and in-vitro toxicological studies, epidemiological studies, quantitative structure-activity relationships (QSAR), and physiologically based toxicokinetic (PBTK) studies.

Toxicology has made a major contribution in providing chemical toxicity information for many years. From a methodology perspective, toxicological test methods range from conventional whole-animal (in-vivo) usage to modern cell culture (in-vitro) techniques. Conventional methods of toxicological assessment are based on whole-animal (in-vivo) studies; indeed, animal toxicity studies began in 1927 when the LD50 (lethal dose 50%) test was introduced by Trevan in the USA [29].

With regard to time of exposure, toxicity studies range from single exposure to short-term and long-term repeated exposure studies. Usually, single-exposure toxicity tests are performed to determine the acute toxicity of chemicals. These toxicity tests often involve the administration of relatively large amounts of chemicals in order to measure an appropriate endpoint such as lethality, organ damage, or cell death. Short-term repeated exposure studies are performed by repeated administration of a chemical in order to determine both subacute toxicity information and to establish doses for longer-term studies. Long-term repeated exposure studies are performed to determine the long-term toxicity of chemicals; these tests often involve the administration of low chemical doses over extended periods in order to establish the cumulative toxicity of the materials.

Conventional animal toxicity tests such as the LD50, have been criticized due to the heavy reliance on animal data. The Organisation for Economic and Cooperative Development (OECD) has modified the LD50 acute oral toxicity test (401) in order to reduce the number of animals used for each test substance [30]. Similarly, in the area of inhalation toxicology, the OECD has also proposed new test guidelines including an Acute Inhalation Toxicity-Fixed Dose Procedure (433) and an Acute Inhalation Toxicity-Acute Toxic Class (ATC) Method (436), both of which are in draft form [31]. These guidelines will replace conventional guidelines including: Acute Inhalation Toxicity (403); Repeated Dose Inhalation Toxicity 28/14-Day (412); and Subchronic Inhalation Toxicity 90-Day (413).

However, the prediction of biological activities of toxic compounds in humans by placing reliance on animal data poses some degree of uncertainty due to inter-species differences between animals and humans [32-34].

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