‘The Dose Makes the Poison’ (or so we are told)

This phrase, ‘the dose makes the poison‘, is attributed to the 15th century physician and alchemist Paracelsus. It  seems that even 600 years ago (and probably long before that) people had noticed that certain poisons might lose some of their sting (and might even prove beneficial) if they were administered in sufficiently low doses.

The debate about the relationship between dose and biological effect has never gone away. Toxicologists who study the health effects of carcinogens, estrogen mimics, radiation, etc., in test animals often rely on considerably higher doses than humans ever encounter. High doses can be justified in several ways, but one rationale that is often given is that the test animals (e.g. mice) have relatively short lifespans. Consequently, the researchers need to apply large doses in order to distinguish between health outcomes caused by their experimental procedure and outcomes that might be associated with the animal’s normal pattern of health and sickness. But this leads to a nagging question, how does one extrapolate from the health hazards revealed by a short term, large dose study in mice to the health hazards that a human might experience through long term, small dose exposure?

Some have argued for a threshold model. This model says exposure to chemicals/radiation below a certain threshold dose has no effect. Harmful effects, advocates say, appear and increase only when exposure exceeds a certain threshold. Others have even suggested exposure to very low doses of toxins can be beneficial. This phenomenon is called hormesis. Many toxicologists, however, say that the scientific difficulties associated with low-dose experiments should not be taken as evidence that low doses are either neutral or beneficial.

Writing on March 12, 2012 in the Advancing Green Chemistry blog, “Low doses, big effects: Scientists seek ‘fundamental changes’ in testing, regulation of hormone-like chemicals,” Marla Cone (editor-in-chief, Environmental Health News) states: “One of the biggest controversies is whether the tiny doses that most people are exposed to are harmful. Researchers led by Tufts University’s Laura Vandenberg concluded after examining hundreds of studies that health effects “are remarkably common” when people or animals are exposed to low doses.” Read the rest of Cone’s post.