Nonmonotonic dose responses (NMDRs) present a challenge to those involved in human health testing and assessment, as they do not follow the expected trend of an increasing dose leading to a proportionally increasing frequency or severity of effect. The US EPA has recently published a draft ‘state of the science’ report, containing a comprehensive review of the relevant literature surrounding NMDRs, focusing on endocrine pathways.

The Agency has concluded that NMDRs do occur, however, they are not commonly identified in vivo, and are rarely seen in whole-organism studies after low-dose or long-term exposure. Significantly, the Agency considers that there is no reproducible evidence that the low-dose key biological events involved in NMDR expression are predictive of adverse outcomes in humans and, as such, the current testing strategies are “highly unlikely to mischaracterize” a chemical that has the potential for endocrine disruption.

US Environmental Protection Agency (EPA). State of the science evaluation: nonmonotonic dose responses as they apply to estrogen, androgen, and thyroid pathways and EPA testing and assessment procedures. Draft. June 2013.

http://epa.gov/ncct/download_files/edr/NMDR.pdf

http://epa.gov/ncct/edr/nas-review.html

 

 

The above item was taken from the August 2013 issue of Toxicology and Regulatory News which is sent automatically to members of bibra (click here for more details).

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