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Low-Dose Effects and Non-Monotonic Dose Responses in Regulatory Science

by Daland Juberg, Ph.D., Dow AgroSciences, and Sue Marty, Ph.D., The Dow Chemical Company

In recent years, there has been significant discussion around low-dose effects (LDEs) and non-monotonic dose-response (NMDR) curves, particularly relative to endocrine disruption. For example, there are claims that crop protection products are associated with LDEs and NMDRs, which question whether current human exposure limits are adequate. These claims present an opportunity for increased dialogue on the relevance of LDEs and NMDRs for chemical risk assessment and regulatory decision-making.


The focus on LDE and NMDR relevance has to be shifted to a different level of thinking and involve 1) clarification on the definition of low dose, 2) recognition of current testing guidelines and risk assessment standards for crop protection products, 3) strength of evidence for LDEs/NMDRs and the relationship to adversity of effect, 4) temporality of dose-response relationships, and 5) placement of any observed LDEs or NMDRs in the context of related endpoints examined in affected system(s) (e.g., endocrine), other systemic endpoints, other available data and the relevance to human and wildlife exposure. The discussion needs to progress from debating whether LDEs or NMDRs exist to their relevance for risk assessment and protection of environmental and human health. What constitutes low dose and what might be termed an effect to some may be different from the perspective of a regulatory scientist who considers an effect in the context of the following: a weight-of-evidence evaluation of available scientific data, determination of whether an effect is adverse or adaptive,[1] where the effect falls relative to the no observed adverse effect level/concentration used for establishment of acceptable exposure levels, and finally, how the effective dose compares to actual human exposure.

Read this full perspective at EndocrineScienceMatter.org. Also, follow @endoscimatters on Twitter.


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