[ RadSafe ] Calabrese 'Paradigm' paper published

[Muckerheide, James]

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