Can Toxicity for Different Species be Correlated?: The Concept and Emerging Applications of Interspecies Quantitative Structure-Toxicity Relationship (i-QSTR) Modeling

Can Toxicity for Different Species be Correlated?: The Concept and Emerging Applications of Interspecies Quantitative Structure-Toxicity Relationship (i-QSTR) Modeling

Supratik Kar (Jackson State University, Jackson, MS, USA), Rudra Narayan Das (Jadavpur University, Kolkata, India), Kunal Roy (Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India) and Jerzy Leszczynski (Jackson State University, MS, USA)
DOI: 10.4018/IJQSPR.2016070102
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Experimental evaluation of the toxicity of a compound is an expensive practice, and it requires sacrifice of a large number of animals. As a consequence, in silico techniques for predictive toxicology are taking the central stage of attention of the scientific community. Interspecies quantitative structure-toxicity relationship (i-QSTR) modeling provides a tool for estimation of contaminant's sensitivity with known levels of uncertainty for a diverse pool of species. It is capable of extrapolating data for one toxicity endpoint to another toxicity endpoint when the data for the second species are unavailable. The emerging i-QSTR approach can overcome the cost of multiple toxicity tests, improve the understanding of the mechanism of toxic action (MOA) of chemicals for different organisms and endpoints and is very useful in order to fill the data gaps where toxicity value for a particular compound is absent for a specific endpoint.
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1. Chemical Toxicity

Chemical toxicity refers to the adverse effects of chemicals on the ecosystem, humans or other living systems in the environment with many dimensions (Colton, 2002). Chemicals are prospective poisons as they can cause injury or death due to their excessive exposure at various concentrations. A chemical may cause irreversible change in homeostasis or increased susceptibility to other chemical or biological stress, functional or anatomical damage, including infectious diseases. Even prolonged and continuous exposure of any so called ‘safe’ chemical may show serious toxicity after years. The continuous increase of the world’s population, combined with industrial progress, has made a significant impact of chemicals (including pharmaceuticals) on the world’s ecosystems and living bodies. As human society depends on so many diverse types and classes of chemicals, it is very imperative to understand the way in which the chemicals interact with the living system and the ecosystem. The magnitude of eco-toxicity of hazardous chemicals, pesticides, agrochemicals, synthetic and semi-synthetic chemicals, dyes, pollutants, pharmaceuticals and food products, is a matter of great concern considering that though huge numbers of compounds are in commercial use, while relatively few of these have been subjected to sufficient evaluation for their hazardous properties to the environment (Cronin et al., 2004, Kar and Roy, 2010a).

Chemicals are commonly characterized into broad classes based on modes of action such as inert chemicals (non-polar narcosis), less-inert chemicals (polar narcosis), reactive chemicals (free-radical formation, weak acid respiratory uncoupling, as well as electrophilic reactions) and specifically acting chemicals (Schultz et al., 2006). The narcosis mode of action is related with reversibly altered structure and function of the cell membranes from non-specific non-covalent interactions with cell membranes. The polar narcotic chemicals are generally more toxic than chemicals which act through non-polar (baseline) toxicity. Reactive chemicals exhibit toxicity in excess of that predicted by either non-polar or polar narcosis (Verhaar et al., 1992). The term “reactive” encompasses a wide spectrum of competing electrophilic and nucleophilic, redox, and free-radical processes (Enoch et al. 2008). The categorization of chemicals according to mechanism of action is a very tedious and complex task (Netzeva et al., 2008). For example, anilines are considered to be narcotics to fish but are more toxic to Daphnia magna (Netzeva et al., 2008). Therefore, the underlying mode of action may completely depend on the exposed species (Jager et al., 2007). The mechanism of (toxic) action (MOA) of the chemicals under investigations should be taken into account during analysis of chemical toxicity for a better understanding. It may be noted here that there may be significant differences between the mode of action and the mechanism of action of a chemical with respect to a specific response. The former is defined in terms of various incompletely characterized biochemical, physiological, or behavioral responses leading to the behavioral changes upon exposure to chemicals, while mechanism of action refers to explicit and detailed understanding of all steps reflecting the necessary sequence of events involved in the manifestation of toxicity of chemicals (Borgert et al., 2004; ECETOC, 2007). However, in this review, we have used the abbreviation MOA for both the terms.

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