In an article published on June 3, 2016 by the news provider CounterPunch, reporter Kristine Mattis discusses the predominant assumption of positive monotonic dose-response (PMDR) employed in current chemical risk assessment versus non-monotonic dose response (NMDR) increasingly observed for substances such as endocrine disrupting chemicals (EDCs). Mattis explains that PMDR presumes “a lowest dose at which a compound produces negligible or no harm to human health” – the so called Lowest Observable Adverse Effect Level (LOAEL). In this manner, increasingly higher doses of a substance are increasingly harmful, whereas increasingly lower doses are insignificantly harmful or not harmful at all. In contrast, in NMDR curves the sign of the response (positive or negative) can change throughout the range of dosages. For example, EDCs can produce adverse effects at very high and very low doses, rather than at in-between doses. Bisphenol A (BPA, CAS 80-05-7) is one example of an EDC for which adverse effects have been shown at low doses in animal studies, but not at higher doses (FPF reported). This behavior is contradictory to the assumption of low dose safety, Mattis explains.

In her article Mattis cites Pete Myers, founder and chief scientist at Environmental Health Sciences, who stated that “NMDR curves are the default expectation for [EDCs].” Regarding the presumption of monotonicity, Myers added that “by ignoring NMDR curves, risk assessment as currently practiced is deeply flawed and unquestionably allows people to be exposed to harmful chemicals at dangerous doses.” Mattis concludes that the paradigm under which chemical risk assessment and regulation currently operate is faulty and inadequately protects human health. Therefore, “assertions by the [U.S. Food and Drug Administration] and [European Food Safety Authority] about the safety of BPA or other toxicants at current levels should be taken with a note of skepticism,” Mattis advises.

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Kristine Mattis (June 3, 2016). “Toxic curve ball: Why outdated assumptions to determine ‘safe levels’ of toxicants forfeit the game.CounterPunch