The dose makes the poison

The dose makes the poison, a principle of toxicology, was first expressed by German-Swiss Renaissance physician Paracelsus. It means that a substance can produce the harmful effect associated with its toxic properties only if it reaches a susceptible biological system within the body in a high enough concentration (dose).

The principle relies on the finding that all chemicals—even water and oxygen—can be toxic if too much is eaten, drunk, or absorbed. ‘The toxicity of any particular chemical depends on many factors, including the extent to which it enters an individual’s body.’ This finding provides also the basis for public health standards, which specify maximum acceptable concentrations of various contaminants in food, public drinking water, and the environment.

However, there is no linear relationship and also more to chemical toxicity than the acute effects caused by short-term exposure. Relatively low doses of contaminants in water, food, and environment can already have significant chronic effects if there is a long-term exposure. Many pollutants, drugs and natural substances adhere to this principle by causing different effects at different levels, which can as a result lead to health standards that are either too strong or too weak.

Generally the effects of different doses can be very different at different levels (not only bigger and smaller impacts depending on dose). Very low doses of some compounds can even induce stronger toxic responses than much higher doses as well as just different impacts.

‘Regulators must extrapolate results not only from animal toxicity studies, typically from mice and/or rats to humans, but also from the very high doses usually used in animal experiments to the very low doses that are characteristic of human exposure. These two types of extrapolation are steeped in uncertainty,’ wrote Edward J. Calabrese, Professor of Toxicology at the University of Massachusetts Amherst’ School of Public Health.

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