Relationship between Dose and Its Effects on Exposed Organism

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Toxicology is a scientific discipline, overlapping with biologychemistrypharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure (whether it is acute or chronic), route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukaemia.

The goal of toxicity assessment is to identify adverse effects of a substance. Adverse effects depend on two main factors: i) routes of exposure (oral, inhalation, or dermal) and ii) dose (duration and concentration of exposure). To explore dose, substances are tested in both acute and chronic models. Generally, different sets of experiments are conducted to determine whether a substance causes cancer and to examine other forms of toxicity.

Factors that influence chemical toxicity:

  • Dosage
    • Both large single exposures (acute) and continuous small exposures (chronic) are studied.
  • Route of exposure
    • Ingestion, inhalation or skin absorption
  • Other factors
    • Species
    • Age
    • Sex
    • Health
    • Environment
    • Individual characteristics

The discipline of evidence-based toxicology strives to transparently, consistently, and objectively assess available scientific evidence in order to answer questions in toxicology, the study of the adverse effects of chemical, physical, or biological agents on living organisms and the environment, including the prevention and amelioration of such effects. Evidence-based toxicology has the potential to address concerns in the toxicological community about the limitations of current approaches to assessing the state of the science. These include concerns related to transparency in decision making, synthesis of different types of evidence, and the assessment of bias and credibility. Evidence-based toxicology has its roots in the larger movement towards evidence-based practices

While testing in animal models remains as a method of estimating human effects, there are both ethical and technical concerns with animal testing.

Since the late 1950s, the field of toxicology has sought to reduce or eliminate animal testing under the rubric of "Three Rs" – reduce the number of experiments with animals to the minimum necessary; refine experiments to cause less suffering, and replace in vivo experiments with other types, or use more simple forms of life when possible.

Computer modeling is an example of alternative testing methods; using computer models of chemicals and proteins, structure-activity relationships can be determined, and chemical structures that are likely to bind to, and interfere with, proteins with essential functions, can be identified. This work requires expert knowledge in molecular modeling and statistics together with expert judgment in chemistry, biology and toxicology.

In 2007 the American NGO National Academy of Sciences published a report called "Toxicity Testing in the 21st Century: A Vision and a Strategy" which opened with a statement: "Change often involves a pivotal event that builds on previous history and opens the door to a new era. Pivotal events in science include the discovery of penicillin, the elucidation of the DNA double helix, and the development of computers. ... Toxicity testing is approaching such a scientific pivot point. It is poised to take advantage of the revolutions in biology and biotechnology. Advances in toxico genomics, bioinformatics, systems biology, epigenetics, and computational toxicology could transform toxicity testing from a system based on whole-animal testing to one founded primarily on in vitro methods that evaluate changes in biologic processes using cells, cell lines, or cellular components, preferably of human origin." As of 2014 that vision was still unrealized.

Regards,
Tony Wilson
Journal Coordinator
American Journal of Pharmacology and Pharmacotherapeutics