Toxicology

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Toxicology (from the Greek words toxicos and logos) is the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.

History
Mathieu Orfila is considered to be the modern father of toxicology, having given the subject its first formal treatment in 1813 in his Trait des poisons, also called Toxicologie generate.

However, Theophrastus Phillipus Auroleus Bombastus von Hohenheim (1493 - 1541) (also referred to as Paracelsus, from his belief that he was above or beyond the work of Celsus - the Roman physician from the first century) is widely regarded as "the father" of toxicology. He is credited with the classic toxicology soundbite "All things are poison and nothing is without poison; only the dose makes a thing a poison." The original German reads: "Alle Dinge sind Gift und nichts ist ohne Gift; allein die Dosis macht, dass ein Ding kein Gift ist." This is often condensed to "The dose makes the poison".

The term LD50 refers to the dose of a toxic substance that kills 50 percent of a test population (typically rats or other surrogates when the test concerns human toxicity). LD50 estimations in animals are no longer required for regulatory submissions as a part of pre-clinical development package.

Relationship between dose and toxicity
Toxicology studies the relationship between dose and its effects on the living organism. The chief criterion regarding the toxicity of a chemical is the dose, i.e. the amount of exposure to the substance. Almost all substances are toxic under the right conditions as Paracelsus, the father of modern toxicology said, “Sola dosis facit venenum” (only dose makes the poison). Paracelsus, who lived in the 16th century, was the first person to explain the dose-response relationship of toxic substances.

Even a benign substance like water can cause harm in excessive amounts. "Dr. Adrian Cohen was saddened, but not surprised, to hear about the 28-year-old woman who died earlier this month after drinking nearly two gallons of water to try to win a radio station contest."

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. Many drug molecules are made toxic in the liver, a good example being acetaminophen (paracetamol), especially in the presence of alcohol. 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 engages many toxicologists 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.