1997 Low dose effects and non-monotonic dose responses identified, shifting the emphasis in EDC research to low-dose effects and non-monotonic dose-responses (NMDRs).
This study showed that relative to estradiol, BPA was not as bound to plasma estrogen-binding proteins in human or mouse blood, resulting in an increase in BPA’s ability to enter cells and cause adverse effects at very low doses previously considered to be safe:
Nagel SC, vom Saal FS, Thayer KA, Dhar MG, Boechler M, Welshons WV. Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. Environ Health Perspect. 1997 Jan;105(1):70-6.
This study found opposite effects at low and high doses; it showed that a 0.1 pg/ml increase in serum estradiol (low dose) stimulated the fetal prostate, while a 1.5 pg/ml increase (high dose) inhibited prostate development. The same low-dose stimulation and high-dose inhibition of prostate development was found for DES:
vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, Dhar MD, Ganjam VK, Parmigiani S, Welshons WV. Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):2056-61.
Estrogens in the Environment IV organized by NIEHS.
Estrogens in the environment, Environ Health Perspect. 1997 Sep;105(9):910.
The International Agency for Research on Cancer (IARC) classified TCDD as a known human carcinogen.