Abstract
The last decade witnessed extraordinary advances in “omics” methods, particularly transcriptomics, proteomics and metabolomics, enabling toxicologists to integrate toxicokinetics and toxicodynamics with mechanistic insights on the mode-of-action of noxious chemicals, single or combined. The toxicology of mixtures is, nonetheless, a most challenging enterprise, especially for environmental toxicologists and ecotoxicologists, who invariably deal with chemical mixtures, many of which contain unknowns. Despite costs and demanding computations, the systems toxicology framework, of which “omics” is a major component, endeavors extracting adverse outcome pathways for complex mixtures. Still, the interplay between the multiple components of gene expression and cell metabolism tends to be overlooked. As an example, the proteome allocates DNA methyltransferases whose altered transcription or loss of function by action of chemicals can have a global impact on gene expression in the cell. On the other hand, chemical insult can produce reactive metabolites and radicals that can intercalate or bind to DNA as well as to enzymes and structural proteins, compromising their activity. These examples illustrate the importance of exploring multiple “omes” and the purpose of “omics” and multi-“omics” for building truly predictive models of hazard and risk. Here we will review the state-of-the-art of toxicogenomics highlighting successes, shortcomings and perspectives for next-generation environmental toxicologists.
Highlights
Expecting that humans and wildlife are exposed to single toxicants or classes of toxicants is unrealistic
As the basic principle upon which Paracelsus set the foundations for modern toxicology, “it is only the dose which makes a thing a poison”, we must be aware that every biological system is constantly exposed to a multitude of potential hazards whose hazards can be higher than the sum of its parts
There are, invaluable cases that determined the toxicity thresholds of specific toxicants of classes of toxicants within complex environmental matrices and mixtures of chemicals. It is the case of the sediment quality guidelines (SQGs) derived by Macdonald et al [7] for major toxicant in marine coastal sediments such as metals, pesticides and polycyclic aromatic hydrocarbons (PAHs), which resulted from empirical models based on vast amounts of chemical and biological data
Summary
Expecting that humans and wildlife are exposed to single toxicants or classes of toxicants is unrealistic. There are, invaluable cases that determined the toxicity thresholds of specific toxicants of classes of toxicants within complex environmental matrices and mixtures of chemicals It is the case of the sediment quality guidelines (SQGs) derived by Macdonald et al [7] for major toxicant in marine coastal sediments such as metals, pesticides and polycyclic aromatic hydrocarbons (PAHs), which resulted from empirical models based on vast amounts of chemical and biological data. Toxicokinetics aims at uptake rates, distribution, metabolization and elimination of noxious chemicals, which unquestionably depends on toxicological mechanism as well Both subdisciplines are regarded as integrated elements of the toxic response, which means that knowledge on both is required to determine exposure and predict the probability of harm, i.e., risk. Even though the relevance of “omics” for studying the toxicology of mixtures has been pointed out years back [16], now is the time to review the subject in face of novel technical achievements, with emphasis on multi-omics approaches, bioinformatics tools, plus their failures and successes in the collusion between traditional and emerging toxicants
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: International Journal of Environmental Research and Public Health
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
