dc.contributor.author | Welshons, Wade V. | eng |
dc.contributor.author | Thayer, Kristina A. (Kristina Ann), 1969- | eng |
dc.contributor.author | Judy, Barbara M. | eng |
dc.contributor.author | Taylor, Julia A. | eng |
dc.contributor.author | Curran, Edward M. (Edward Michael), 1949- | eng |
dc.contributor.author | vom Saal, Frederick S. | eng |
dc.date.issued | 2003 | eng |
dc.description | Reproduced with permission from Environmental Health Perspectives. doi:10.1289/ehp.5494 | eng |
dc.description.abstract | Information concerning the fundamental mechanisms of action of both natural and environmental hormones, combined with information concerning endogenous hormone concentrations, reveals how endocrine-disrupting chemicals with estrogenic activity (EEDCs) can be active at concentrations far below those currently being tested in toxicological studies. Using only very high doses in toxicological studies of EEDCs thus can dramatically underestimate bioactivity. Specifically: a) The hormonal action mechanisms and the physiology of delivery of EEDCs predict with accuracy the low-dose ranges of biological activity, which have been missed by traditional toxicological testing. b) Toxicology assumes that it is valid to extrapolate linearly from high doses over a very wide dose range to predict responses at doses within the physiological range of receptor occupancy for an EEDC; however, because receptor-mediated responses saturate, this assumption is invalid. c) Furthermore, receptor-mediated responses can first increase and then decrease as dose increases, contradicting the assumption that dose-response relationships are monotonic. d) Exogenous estrogens modulate a system that is physiologically active and thus is already above threshold, contradicting the traditional toxicological assumption of thresholds for endocrine responses to EEDCs. These four fundamental issues are problematic for risk assessment methods used by regulatory agencies, because they challenge the traditional use of extrapolation from high-dose testing to predict responses at the much lower environmentally relevant doses. | eng |
dc.description.sponsorship | Support during the preparation of this manuscript was provided by the W. Alton Jones Foundation to K.A.T, as well as by grants from the National Institutes of Health (NIH) (CA50354) and the University of Missouri (VMFC0018) to W.V.W and NIH (ES08293 and ES11283), U.S. Environmental Protection Agency (U914991), and University of Missouri Research Board to F.v.S. | eng |
dc.identifier.citation | Welshons WV, Thayer KA, Judy BM, Taylor JA, Curran EM, et al. 2003 Large Effects from Small Exposures. I. Mechanisms for Endocrine-Disrupting Chemicals with Estrogenic Activity. Environmental Health Perspectives 111(8): 994-1006. | eng |
dc.identifier.uri | http://hdl.handle.net/10355/10164 | eng |
dc.language | English | eng |
dc.publisher | National Institute of Environmental Health Sciences | eng |
dc.relation.ispartof | Biomedical Sciences publications (MU) | eng |
dc.relation.ispartofcommunity | University of Missouri-Columbia. College of Veterinary Medicine. Department of Biomedical Sciences | eng |
dc.subject | chemical exposure | eng |
dc.subject | environmental chemicals | eng |
dc.subject.lcsh | Endocrine disrupting chemicals -- Mechanism of action | eng |
dc.subject.lcsh | Estrogen -- Receptors | eng |
dc.subject.lcsh | Hormone receptors | eng |
dc.subject.lcsh | Fetus -- Development | eng |
dc.title | Large Effects from Small Exposures. I. Mechanisms for Endocrine-Disrupting Chemicals with Estrogenic Activity | eng |
dc.type | Article | eng |