[ RadSafe ] Calabrese 'Paradigm' paper published
Muckerheide, James
jimm at WPI.EDU
Thu Aug 11 14:32:31 CDT 2005
Friends,
This paper is now published with issue and page numbers. Please share with
colleagues who should know about the state of the science.
Let me know if you want the published PDF for review.
Regards, Jim Muckerheide
===================
Environmental Pollution 138 (2005) 379-412
Invited paper
Paradigm lost, paradigm found: The re-emergence of
hormesis as a fundamental dose response model
in the toxicological sciences
Edward J. Calabrese*
Environmental Health Sciences, School of Public Health, Morrill I, N344,
University of Massachusetts, Amherst, MA 01003, USA
Received 1 September 2004; accepted 5 October 2004
The quantitative features of the hormetic dose/response are described and
placed within the context of toxicology.
Abstract
This paper provides an assessment of the toxicological basis of the hormetic
dose-response relationship including issues relating
to its reproducibility, frequency, and generalizability across biological
models, endpoints measured and chemical class/physical
stressors and implications for risk assessment. The quantitative features of
the hormetic dose response are described and placed
within toxicological context that considers study design, temporal
assessment, mechanism, and experimental model/population
heterogeneity. Particular emphasis is placed on an historical evaluation of
why the field of toxicology rejected hormesis in favor of
dose response models such as the threshold model for assessing
non-carcinogens and linear no threshold (LNT) models for assessing
carcinogens. The paper argues that such decisions were principally based on
complex historical factors that emerged from the
intense and protracted conflict between what is now called traditional
medicine and homeopathy and the overly dominating
influence of regulatory agencies on the toxicological intellectual agenda.
Such regulatory agency influence emphasized hazard/risk
assessment goals such as the derivation of no observed adverse effect levels
(NOAELs) and the lowest observed adverse effect levels
(LOAELs) which were derived principally from high dose studies using few
doses, a feature which restricted perceptions and
distorted judgments of several generations of toxicologists concerning the
nature of the dose-response continuum. Such historical
and technical blind spots lead the field of toxicology to not only reject an
established dose-response model (hormesis), but also the
model that was more common and fundamental than those that the field
accepted.
_ 2004 Elsevier Ltd. All rights reserved.
Keywords: Hormesis; U-shaped; J-shaped; Homeopathy; Dose-response; Biphasic;
Risk assessment; Threshold; Linearity; History of science;
History of medicine; Toxicology
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