is a scientific discipline involving the study of structure and mechanism related to the toxic effects of chemical agents, and encompasses technology advances in
research related to chemical aspects of toxicology. Research in this area is discovery, drug metabolism and mechanisms of action, bioinformatics, bioanalytical
chemistry, chemical biology, and molecular epidemiology.
Toxicity of metabolites
Many substances regarded as poisons are toxic only indirectly. An example is "wood alcohol," or methanol, which is chemically converted to formaldehyde and formic
acid in the liver. It is the formaldehyde and formic acid that cause the toxic effects of methanol exposure. As for drugs, many small molecules are made toxic in the
liver, a good example being acetaminophen (paracetamol), especially in the presence of chronic alcohol use. The genetic variability of certain liver enzymes makes
the toxicity of many compounds differ between one individual and the next. Because demands placed on one liver enzyme can induce activity in another, many
molecules become toxic only in combination with others. A family of activities that many toxicologists engage includes identifying which liver enzymes convert a
molecule into a poison, what are the toxic products of the conversion and under what conditions and in which individuals this conversion takes place.
Subdisciplines of toxicology
There are various specialized subdisciplines within the field of toxicology that concern diverse chemical and biological aspects of this area. For example,
toxicogenomics involves applying molecular profiling approaches to the study of toxicology. Other areas include Aquatic toxicology, Chemical toxicology,
Ecotoxicology, Environmental toxicology, Forensic toxicology, and Medical toxicology.
is the study of the effects of manufactured chemicals and other anthropogenic and natural materials and activities on aquatic organisms at various levels of
organization, from subcellular through individual organisms to communities and ecosystems (Rand, 1995).In the United States aquatic toxicology plays an important
role in the NPDES wastewater permit program. In additional to analytical testing for known pollutants, aquatic, whole effluent toxicity tests have been standardized
and are performed routinely as a tool for evaluating the potential harmful effects of effluents discharged into surface waters.
Environmental Toxicology (EnTox)
EnTox is a young (1965) and interdisciplinary science that uses both basic and applied scientific knowledge to understand natural and anthropogenic pollutants life
cycle and their impacts upon structure and functions of biological and ecological systems. Research in EnTox includes both laboratory experiments and field studies.
EnTox wants to answer two main questions, How the release pollutant causes harmful effects? What can we do to prevent or minimize risk to biological and
Is the use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal investigation of death,
poisoning, and drug use. The primary concern for forensic toxicology is not the legal outcome of the toxicological investigation or the technology utilised, but rather
the obtaining and interpreting of the results. A toxicological analysis can be done to various kinds of samples.
A forensic toxicologist must consider the context of an investigation, in particular any physical symptoms recorded, and any evidence collected at a crime scene that
may narrow the search, such as pill bottles, powders, trace residue, and any available chemicals. Provided with this information and samples with which to work, the
forensic toxicologist must determine which toxic substances are present, in what concentrations, and the probable effect of those chemicals on the person.
Determining the substance ingested is often complicated by the body's natural processes (see ADME), as it is rare for a chemical to remain in its original form once in
the body. For example: heroin is almost immediately metabolised into another substance and further to morphine, making detailed investigation into factors such as
injection marks and chemical purity necessary to confirm diagnosis. The substance may also have been diluted by its dispersal through the body; while a pill or other
regulated dose of a drug may have grams or milligrams of the active constituent, an individual sample under investigation may only contain micrograms or
In vitro toxicity testing
is the scientific analysis of the effects of toxic chemical substances on cultured bacteria or mammalian cells. In vitro (literally 'in glass') testing methods are employed
primarily to identify potentially hazardous chemicals and/or to confirm the lack of certain toxic properties in the early stages of the development of potentially useful
new substances such as therapeutic drugs, agricultural chemicals and direct food additives that may or may not taste good.
Most toxicologists believe that in vitro toxicity testing methods can be a useful, time and cost-effective supplement to toxicology studies in living animals (which are
termed in vivo or "in life" methods). However, it is generally accepted that the available in vitro tests are not presently adequate to entirely replace animal
In vitro assays for xenobiotic toxicity are recently carefully considered by key government agencies (e.g. EPA; NIEHS/NTP; FDA), mainly due to a societal movement
to reduce the use of animals in research, and a desire to better assess human risks. There are substantial activities in using in vitro systems to advance mechanistic
understanding of toxicant activities, and the use of human cells and tissue to define human-specific toxic effects.
in toxicology, refers to a tendency to take a drug over and over again, forgetting each time that one has already taken the dose. This can lead to a cumulative
overdose. A particular example is barbiturates which were once commonly used as hypnotic (sleep inducing) drugs. Among the current hypnotics, benzodiazepines,
especially midazolam might show marked automatism, possibly through their intrinsic anterograde amnesia effect.
The term ecotoxicology was coined by René Truhaut in 1969 who defined it as "the branch of toxicology concerned with the study of toxic effects, caused by natural
or synthetic pollutants, to the constituents of ecosystems, animal (including human), vegetable and microbial, in an integral context” (Truhaut, 1977).
is the integration of toxicology and ecology or, as Chapman (2002) suggested, “ecology in the presence of toxicants”. It aims to quantify the effects of stressors
upon natural populations, communities, or ecosystems. Ecotoxicology differs from environmental toxicology in that it integrates the effects of stressors across all
levels of biological organisation from the molecular to whole communities and ecosystems, whereas environmental toxicology focuses upon effects at the level of the
individual and below (Maltby & Naylor, 1990). This broader remit is distinct from the anthropocentric nature of classical toxicology and the legislative approach of
environmental toxicology. Ecotoxicology incorporates aspects of ecology, toxicology, physiology, molecular biology, analytical chemistry and many other disciplines.
The ultimate goal of this approach is to be able to predict the effects of pollution so that the most efficient and effective action to prevent or remediate any
detrimental effect can be identified. In those ecosystems that are already impacted by pollution ecotoxicological studies can inform as to the best course of action to
restore ecosystem services and functions efficiently and effectively.
In forensic entomology
Entomotoxicology is the analysis of toxins in arthropods (mainly flies and beetles) that feed on carrion. Using arthropods in a corpse or at a crime scene,
investigators can determine whether toxins were present in a body at the time of death. This technique is a major advance in forensics; previously, such
determinations were impossible in the case of severely decomposed bodies devoid of intoxicated tissue and bodily fluids. Ongoing research into the effects of toxins
on arthropod development has also allowed better estimations of postmortem intervals.
is a field of science that deals with the collection, interpretation, and storage of information about gene and protein activity within particular cell or tissue of an
organism in response to toxic substances. Toxicogenomics combines toxicology with genomics or other high throughput molecular profiling technologies such as
transcriptomics, proteomics and metabolomics. Toxicogenomics endeavors to elucidate molecular mechanisms evolved in the expression of toxicity, and to derive
molecular expression patterns
(i.e., molecular biomarkers) that predict toxicity or the genetic susceptibility to it.
In pharmaceutical research toxicogenomics is defined as the study of the structure and function of the genome as it 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 (Lesko and Woodcock 2004, Lesko
et al. 2003). Though the term toxicogenomics first appeared in the literature in 1999 (Nuwaysir et al.) it was already in common use within the pharmaceutical
industry as its origin was driven by marketing strategies from vendor companies. The term is still not universal accepted, and others have offered alternative terms
such as chemogenomics to describe essentially the same area (Fielden et al., 2005).
The nature and complexity of the data (in volume and variability) demands highly developed processes for of automated handling and storage. The analysis usually
involves a wide array of bioinformatics and statistics., regularly involving classification approaches.
In pharmaceutical Drug discovery and development toxicogenomics is used to study adverse, i.e. toxic, effects, of pharmaceutical drugs in defined model systems in
order to draw conclusions on the toxic risk to patients or the environment. Both the EPA and the U.S. Food and Drug Administration currently preclude basing
regulatory decision making on genomics data alone. However, they do encourage the voluntary submission of well-documented, quality genomics data. Both
agencies are considering the use of submitted data on a case-by-case basis for assessment purposes (e.g., to help elucidate mechanism of action or contribute to a
weight-of-evidence approach) or for populating relevant comparative databases by encouraging parallel submissions of genomics data and traditional toxicologic
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