What is the wisdom in “It’s the dose that determines that a thing is not a poison”?

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One of the most famous expressions in toxicology is “It’s the dose that determines that a thing is not a poison.” It was uttered in self-defence by a Swiss physician known as Paracelsus, actually Philippus Aureolus Theobrastus Bombastus von Hohenheim in the sixteenth century. He had used mercury salts to treat syphilis, for which they have a modest effect. He was accused of poisoning his patients, and he wrote as his defence: "Was ist das nit gifft ist, alle ding sind gifft, und nichts ohn gifft. Allein die dosis macht das ein ding kein gift ist" (What is not a poison? Everything is poisonous. It’s the dose that determines that a thing is not a poison).

Experimental toxicology has proven how right Paracelsus was over four hundred years ago. In animal experiments, every single chemical can be shown to be toxic, even life-threatening, if the dose is high enough. An American scientist Bruce Ames surveyed many carcinogenicity studies, and found that about half of chemicals could be said to cause cancer, if given to animals in long-term experiments at the maximal doses tolerated. The likelihood of cancer for natural compounds was not very different from that of synthetic chemicals. Thus also long-term effects such as cancer-causing properties depend on the dose and not on the name or origin of the chemical.

Different chemicals have very different potencies. Aflatoxin or dioxin may be dangerous already at doses of one millionth of a gram. On the other hand, there are some compounds, even pesticides, that are tolerated by experimental animals at levels of several grams per kilogram body weight. The statement that all chemicals are poisons does not mean that they are poisonous at the same dose. It only means that completely safe chemicals do not exist, neither synthetic chemicals nor natural substances. Therefore the risk must be viewed relative to their typical doses or exposures.

Safety margin

We have seen that it is not important if a substance is poisonous or not poisonous. It is not even important how poisonous it is. The important thing is, how large the exposure dose is relative to the poisonous dose. If the toxic dose of dioxin is one millionth of a gram, and the dose to which people are exposed is one thousand millionth of a gram, there is a thousand-fold difference between the toxic dose and the actual dose. We say that there is a thousand-fold safety margin.

However, if the safe dose of table salt is less than five grams per day, and we consume every day 15 grams, we should be worried. There is no safety margin. Or to take an even more mundane example, if the lethal dose of alcohol is 300 grams, and we drink 100 grams at a single session, we are frighteningly close to the lethal dose. This tiny safety margin, threefold, would be out of question if it was proposed for most chemicals. Thus the fact that alcohol has relatively low toxicity does not mean that it is not deadly dangerous stuff, if the dose is high.

Knowing that a substance is poisonous does not help much. The crucial point is the dose compared with the toxic dose causing death or adverse effects. It is the distance between the toxic dose and the actual dose which determines the safety margin.

One level up: Perception of the risks around us

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