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The “low dose hypothesis”: what it means in theory and practice

In order to evaluate the toxicity of a chemical substance, scientists test a wide range of doses – from very low to very high doses. Complex terms such “monotonic dose response” or “low dose theory” relate to potential effects that may occur at different doses. But what are these complex theories actually about?

  • “Monotonic dose response”: A conventional dose-response-reaction, also called “monotonic dose response”, shows a consistent increase in (adverse) effects as the dose increases.
  • “Non-Monotonic Dose-Rose”(NMDR): This is a theory which has been gaining coverage over the past years which claims that effects may occur only at specific doses but not at higher or lower concentrations. So contrary to the consistent increase in the monotonic dose response, this theory sees peaks at different doses, either high, low or at several points.
  • “Low-dose theory”: Within the context of the NMDR theory, the idea that some chemicals can cause a biological response only at low dose levels is commonly called the “low dose hypothesis”.

What is the latest state of science?

In May 2016, a study in the context of food safety was commissioned by the European Food Safety Authority (EFSA), and carried out by scientists from renowned national food safety and research institutes, which refuted the low dose theory. The institutions that undertook the study comprised the Austrian Agency for Health and Food Safety GmhH (AGES), the French Agency for Food, Environment and Occupational Health & Safety (ANSES), the Dutch National Institute for Public Health and the Environment (RIVM), and the Swedish Institute of Environmental Medicine, Karolinska Institutet (IMM).

Performing a complex and complete scientific review of literature since 2002, the agencies included over 10,000 studies looking for potential evidence of NMDR. The review did not find plausible evidence for non-monotonic dose-response effects for substances in the area of food safety.

Can the low-dose theory apply to BPA?

People are incidentally exposed to BPA in miniscule amounts. Some researchers have turned to the low dose theory to argue that BPA is harmful at low doses. Such studies were repeatedly judged by independent regulators as unreliable for use in the context of risk assessment for human health. In fact, none of the studies claiming such low dose effects for BPA could be reproduced by other scientist teams; however, reproducibility of scientific results by other teams is a key factor to assess a study’s scientific added value. At the same time, it should be noted that several comprehensive studies that investigated the question of potential effects of very low levels of BPA on the metabolism and looked at several generations of testing subjects, concluded that there are no low-dose effects for BPA.

If NMDR is not an issue we should worry about, then why do scientists claim that low doses of BPA can be bad for us? Thousands of experimental studies have been presented on the most individual questions or endpoints, very often using only few animals, or applying unusual methods for which there is no comparison or experience available. Furthermore, experimental data almost always contain statistical errors. In the context of NMDR, these statistical errors would be considered as real effects, not as statistical outliers. It is therefore even more important that robust science and reliable statistical evaluation is applied in order to validate experimental findings and separate valid results from “false positives”. High standards for assessment and quality of outcomes would reduce uncertainty and address the sometimes arbitrary nature of how research is analysed.

See also:

Science & Risk Assessment

BPA Safety

EFSA NMDR report