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Nonmonotonic Dose Response Curves (NMDRCs) Common after Estrogen or Androgen Signaling Pathway Disruption: Fact or Falderal?
Citation:
Gray, E. Nonmonotonic Dose Response Curves (NMDRCs) Common after Estrogen or Androgen Signaling Pathway Disruption: Fact or Falderal? Presented at SOT 2013 annual meeting, March 10 - 14, 2013.
Impact/Purpose:
Symposium presentation on the shape of the dose response curve for endocrine distupters in the low dose range at the annual SOT 2013 meeting. Highly attended presentations on a controversial issue in toxicology of great interest to the EPA program offices
Description:
EDCs appear to induce some effects that do not appear to display a threshold (apparent Linear No Threshold responses) NMDRCs for EDCs Biologically plausible Occur frequently in vitro, but these are generally not relevant to in vivo effects and do not occur at low concentrations It appears that NMRDCs are more common in studies with short-term exposures and On “upstream” mechanistic events versus “downstream” adverse phenotypic effects. A few of the effects of androgens given sc are non-monotonic, but other effects in the same study occur at lower dosage levels and they display “normal” (monotonic) dose responses A number of multigenerational studies of estrogens and antiandrogens have been reviewed. To date, these did not indicate that robust, reproducible NMDRCs were common events at low dosage levels. Additional data needs to be examined from robust, multigenerational studies using a broad range of dosage levels for other pathways.