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Toxicity
Toxicity

Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism.[1] Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell (cytotoxicity) or an organ such as the liver (hepatotoxicity). By extension, the word may be metaphorically used to describe toxic effects on larger and more complex groups, such as the family unit or society at large. Sometimes the word is more or less synonymous with poisoning in everyday usage.

A central concept of toxicology is that the effects of a toxicant are dose-dependent; even water can lead to water intoxication when taken in too high a dose, whereas for even a very toxic substance such as snake venom there is a dose below which there is no detectable toxic effect. Considering the limitations of this dose-response concept, a novel Drug Toxicity Index (DTI) [22] has been proposed recently.[2] DTI redefines drug toxicity, identifies hepatotoxic drugs, gives mechanistic insights, predicts clinical outcomes and has potential as a screening tool. Toxicity is species-specific, making cross-species analysis problematic. Newer paradigms and metrics are evolving to bypass animal testing, while maintaining the concept of toxicity endpoints.[3]

Types


There are generally four types of toxic entities; chemical, biological, physical and radiation:

  • The R.M.Yassine Scale is the main scale used to measure toxicity.
  • Chemical toxicants include inorganic substances such as, lead, mercury, hydrofluoric acid, and chlorine gas, and organic compounds such as methyl alcohol, most medications, and poisons from living things. While some weakly radioactive substances, such as uranium, are also chemical toxicants, more strongly radioactive materials like radium are not, their harmful effects (radiation poisoning) being caused by the ionizing radiation produced by the substance rather than chemical interactions with the substance itself.
  • Disease-causing microorganisms and parasites are toxic in a broad sense, but are generally called pathogens rather than toxicants. The biological toxicity of pathogens can be difficult to measure because the "threshold dose" may be a single organism. Theoretically one virus, bacterium or worm can reproduce to cause a serious infection. However, in a host with an intact immune system the inherent toxicity of the organism is balanced by the host's ability to fight back; the effective toxicity is then a combination of both parts of the relationship. In some cases, e.g. cholera, the disease is chiefly caused by a nonliving substance secreted by the organism, rather than the organism itself. Such nonliving biological toxicants are generally called toxins if produced by a microorganism, plant, or fungus, and venoms if produced by an animal.
  • Physical toxicants are substances that, due to their physical nature, interfere with biological processes.
  • As already mentioned, radiation can have a toxic effect on organisms.[4]

Measuring


Toxicity can be measured by its effects on the target (organism, organ, tissue or cell).

Assessing all aspects of the toxicity of cancer-causing agents involves additional issues, since it is not certain if there is a minimal effective dose for carcinogens, or whether the risk is just too small to see. In addition, it is possible that a single cell transformed into a cancer cell is all it takes to develop the full effect (the "one hit" theory).

It is more difficult to determine the toxicity of chemical mixtures than a pure chemical, because each component displays its own toxicity, and components may interact to produce enhanced or diminished effects.

The preclinical toxicity testing on various biological systems reveals the species-, organ- and dose- specific toxic effects of an investigational product.

Classification


For substances to be regulated and handled appropriately they must be properly classified and labelled.

Global classification looks at three areas: Physical Hazards (explosions and pyrotechnics),[8] Health Hazards[9] and environmental hazards.[10]

The types of toxicities where substances may cause lethality to the entire body, lethality to specific organs, major/minor damage, or cause cancer.

Acute toxicity looks at lethal effects following oral, dermal or inhalation exposure.

Note: The undefined values are expected to be roughly equivalent to the category 5 values for oral and dermal administration.

Skin corrosion and irritation are determined though a skin patch test analysis. This examines the severity of the damage done; when it is incurred and how long it remains; whether it is reversible and how many test subjects were affected.

Skin corrosion from a substance must penetrate through the epidermis into the dermis within four hours of application and must not reverse the damage within 14 days. Skin irritation shows damage less severe than corrosion if: the damage occurs within 72 hours of application; or for three consecutive days after application within a 14-day period; or causes inflammation which lasts for 14 days in two test subjects. Mild skin irritation minor damage (less severe than irritation) within 72 hours of application or for three consecutive days after application.

Serious eye damage

  • Respiratory sensitizers cause breathing hypersensitivity when the substance is inhaled.
  • A substance which is a skin sensitizer causes an allergic response from a dermal application.
  • Carcinogens induce cancer, or increase the likelihood of cancer occurring.
  • Reproductively toxic substances cause adverse effects in either sexual function or fertility to either a parent or the offspring.
  • Specific-target organ toxins damage only specific organs.
  • Aspiration hazards are solids or liquids which can cause damage through inhalation.

An Environmental hazard can be defined as any condition, process, or state adversely affecting the environment.

  • Water: detergents, fertilizer, raw sewage, prescription medication, pesticides, herbicides, heavy metals, PCBs
  • Soil: heavy metals, herbicides, pesticides, PCBs
  • Air: particulate matter, carbon monoxide, sulfur dioxide, nitrogen dioxide, asbestos, ground-level ozone, lead (from aircraft fuel, mining, and industrial processes)[11]

The EPA maintains a list of priority pollutants for testing and regulation.[12]

The expression "Mad as a hatter" and the "Mad Hatter" of the book Alice in Wonderland derive from the known occupational toxicity of hatters who used a toxic chemical for controlling the shape of hats.

Hazards in the arts have been an issue for artists for centuries, even though the toxicity of their tools, methods, and materials was not always adequately realized.

20th century printmakers and other artists began to be aware of the toxic substances, toxic techniques, and toxic fumes in glues, painting mediums, pigments, and solvents, many of which in their labelling gave no indication of their toxicity.

There are many environmental health mapping tools.

Aquatic toxicity testing subjects key indicator species of fish or crustacea to certain concentrations of a substance in their environment to determine the lethality level. Fish are exposed for 96 hours while crustacea are exposed for 48 hours. While GHS does not define toxicity past 100 mg/l, the EPA currently lists aquatic toxicity as "practically non-toxic" in concentrations greater than 100 ppm.[16]

Note: A category 4 is established for chronic exposure, but simply contains any toxic substance which is mostly insoluble, or has no data for acute toxicity.

Factors influencing toxicity


Toxicity of a substance can be affected by many different factors, such as the pathway of administration (whether the toxicant is applied to the skin, ingested, inhaled, injected), the time of exposure (a brief encounter or long term), the number of exposures (a single dose or multiple doses over time), the physical form of the toxicant (solid, liquid, gas), the genetic makeup of an individual, an individual's overall health, and many others.

Etymology


"Toxic" and similar words came from Greek τοξον = "bow (weapon)" via "poisoned arrow", which came to be used for "poison" in scientific language, as the usual Classical Greek word ('ιον) for "poison" would transliterate to "io-", which is not distinctive enough. In some biological names, "toxo-" still means "bow", as in Toxodon

See also


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