In recent years, a hypothesis has been advanced claiming that exposure to extremely low doses of certain substances could cause adverse health effects in humans, whereas no effects would be seen at higher doses of the same substance. It is also described as ”non-monotonic dose-response“ curve. In toxicity testing on animals, a conventional "monotonic dose-response" shows a consistent increase in (adverse) effects along the dose range. The slope of a NMDR curve, however, changes direction along the dose interval studied resulting, for example, in U-shaped or inverted U-shaped curves. Low dose effects are non-monotonic responses occurring at lower doses than those used in regulatory toxicity studies. Bisphenol A is often named as an example of this hypothesis.
This "low-dose hypothesis" has been thoroughly tested for bisphenol A (BPA) with a series of comprehensive and carefully conducted studies. These comprehensive studies were undertaken by governmental bodies, independent laboratories and industry, using accepted test methods and rigorous Good Laboratory Practice (GLP) guidelines.
The weight of scientific evidence provided by these studies clearly supports the safety of BPA-based applications. In no case could the results of the so called "low dose studies" be reproduced. However, the results of comprehensive multigenerational studies using accepted measures and quality protocols provide strong reassurance that there is no basis for human health concerns from exposure to low doses of BPA.
In May 2016, a new most comprehensive report about the non-monotonic dose response (NMDR) hypothesis was published. The overall conclusion is that “(…) NMDR as a common phenomenon is so far not supported for substances in the area of food safety.”
The report had been commissioned by EFSA and was carried out by four member state organisations: the Austrian Agency for Health and Food Safety GmhH (AGES), the French Agency for Food, Environment and Occupational Health & Safety (ANSES), the Institute of Environmental Medicine, Karolinska Institutet (IMM), Sweden, and the National Institute for Public Health and the Environment (RIVM), Netherlands.
The experts undertook a critical review of more than 10.000 peer-reviewed pieces of scientific literature that had appeared since 2002 for substances in the area of food safety. A pre-defined set of criteria and a systematic review methodology was applied. This included a review of previous reports published on the issue of NMDRs, followed by a thorough literature search to identify relevant in vivo, in vitro and epidemiological/human studies.
The report found that none of the many peer reviewed publications on Bisphenol A (BPA) in the context of NMDR fulfill all predefined criteria and checkpoints the involved experts agreed upon to select studies, that could contribute to a reliable assessment of the presumed existence of the non-monotonic dose-response in food contact. Specifically, the comprehensive review gives no plausible scientific evidence of NMDR (non-monotonic dose-response) with regard to BPA.
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