Toxicogenomics

In the area of toxicology, the subdiscipline of toxicogenomics has emerged, which is the use of genome-scale mRNA expression profiling to monitor responses to adverse xenobiotic exposure. Toxicogenomics is being investigated for use in the triage of compounds through predicting potential toxicity, defining mechanisms of toxicity, and identifying potential biomarkers of toxicity. Whereas various approaches have been reported for the development of algorithms predictive of toxicity and for the interpretation of gene expression data for deriving mechanisms of toxicity, there are no clearly defined methods for the discovery of biomarkers using gene expression technologies. Ways in which toxicogenomics may be used for biomarker discovery include analysis of large databases of gene expression profiles followed by in silico mining of the database for differentially expressed genes; the analysis of gene expression data from preclinical studies to find differentially expressed genes that correlate with pathology (coincident biomarker) or precede pathology (leading biomarker) within a lead series; or gene expression profiling can be performed directly on the blood from preclinical studies or clinical trials to find biomarkers that can be obtained noninvasively. This chapter broadly discusses the issues and the utility of applying toxicogenomics to biomarker discovery.

These studies revealed two main points: first, that toxicity in animals may be likely to also be present in humans, though this cannot be considered particularly consistent or reliable, due to considerable variability and lack of any clear pattern in types of toxic effects; and secondly, perhaps more crucially, that the absence of toxicity in animals provides essentially no insight into the likelihood of toxicity or absence of toxicity in humans. Pharmacokinetics involves the study of absorption, distribution, metabolism, excretion and toxicity of xenobiotics (ADME-Tox). In this sense, the ADME-Tox profile of a bioactive compound can impact its efficacy and safety. Moreover, efficacy and safety were considered some of the major causes of clinical failures in the development of new chemical entities. In this context, machine learning (ML) techniques have been often used in ADME-Tox studies due to the existence of compounds with known pharmacokinetic properties available for generating predictive models.

An adverse outcome pathway (AOP) is structured representation of biological events leading to adverse effects and is considered relevant to risk assessment. The AOP links in a linear way existing knowledge along one or more series of causally connected key events (KE) between two points — a molecular initiating event (MIE) and an adverse outcome (AO) that occur at a level of biological organization relevant to risk assessment. The linkage between the events is described by key event relationships (KER) that describe the causal relationships between the key events. AOPs are important for expanding the use of mechanistic toxicological data for risk assessment and regulatory applications.

The Cardiovascular Toxicology is the field of Toxicology that deals and studies with the agonistic and antagonistic impacts on the blood circulatory system which result from the introduction to chemicals. It is the study about the information of the hindrance actions of the newly introduced cardiovascular drugs. Some of the drugs whose impact is on Circulations and Central nervous system which ultimately affect that centres heart rhythm such as Arrhythmia or might as well cause cardiogenic shock or death or sometimes they show effect indirectly on circulation by inducing effects on Blood pressure which might be due to associated arrhythmias. Thus the study of these effect and related consequences has been a breakthrough in the phase of Cardiology and Toxicology.

Toxicopathology is the analysis, investigation, development of risk assessment and risk management of the changes in the structural and functional aspects of cells, tissues, and organs that are caused by toxins, poisons, and physical operators and policies based on such information. Toxicopathology primarily deals with the mechanism by which this functional and the structural effect is induced. The session of Toxicopathology mainly covers the overall knowledge gain about the effects of toxins and different chemicals that effects on the various functions of the structural and functional units in the human body.

Genetic toxicology is a branch of the field of toxicology that assesses the effects of chemical and physical agents on the hereditary material (DNA) and on the genetic processes of living cells. Such effects can be assessed directly by measuring the interaction of agents with DNA or more indirectly through the assessment of DNA repair or the production of gene mutations or chromosome alterations. It is important at the outset to distinguish between genotoxicity and mutagenicity. Genotoxicity covers a broader spectrum of endpoints than mutagenicity. For example, unscheduled DNA synthesis (UDS), sister chromatid exchanges (SCEs), and DNA strand breaks are measures of genotoxicity, not mutagenicity because they are not themselves transmissible from cell to cell or generation to generation.

Genomic Approaches for Cross-Species Extrapolation in Toxicology provides a balanced discussion drawn from the experience of thirty-five scientists and professionals from diverse fields including environmental toxicology and chemistry, biomedical toxicology, molecular biology, genetics, physiology, bioinformatics, computer science, and statistics. Predictive toxicology is the study of how toxic effects observed in model systems (or humans) can be used to predict pathogenesis, assess risk, and prevent human disease. Improving risk assessment is an essential aim of predictive toxicology.

Reproductive and Developmental Toxicology, is a comprehensive and authoritative study that deals with parent, placenta, and foetus and the continuous changes that occur in each and relation to discussing a broad range of topics, including nanoparticles and radiation, gases and solvents, smoking, alcohol and drug abuse, and metals, amongst others along With a special focus on placental toxicity. Reproductive toxicity includes the effects of a toxic substance on the reproductive ability of an organism and later stages of development of the offspring and as well referred to as an adverse effects of chemicals substances on sexual functioning and fertility in reproducing individuals, as well as later developmental toxicity which is noticed in the offspring. Developmental toxicity refers to the adverse effects induced during the stages of pregnancy, or as a result of parental exposure to chemicals during pregnancy or at any point in the life span of the organism during its stages of development.

 Toxicgenomics is a sub discipline of pharmacology that deals with the collection, interpretation, and storage of information about gene and protein activity within a particular cell or tissue of an organism in response to exposure to toxic substances. Toxicogenomics is defined as the application of genomic technologies (for example, genetics, genome sequence analysis, gene expression profiling, proteomics, metabolomics, and related approaches) to study the adverse effects of environmental and pharmaceutical chemicals on human health and the environment. Toxicogenomics may lead to information that is more discriminating, predictive, and sensitive than that currently used to evaluate toxic exposure or predict effects on human health.

Toxicogenomics is defined as the study of the structure and function of the genome and its responds to adverse xenobiotic exposure. It is the toxicological subdiscipline of pharmacogenomics, which is broadly defined as the study of inter-individual variations in whole-genome or candidate gene single-nucleotide polymorphism maps, haplotype markers, and alterations in gene expression that might correlate with drug responses.