Preface
In May 1990 a group of scientists representing several federal agencies,
the International Society of Regulatory Toxicology and Pharmacology, the
private sector, and academia met to develop a strategy to encourage the
study of the biological effects of low level exposures (BELLE) to chemical
agents and radioactivity. The meeting was convened because of the recogni
tion that most human exposures to chemical agents and radioactivity are at
low levels, yet most toxicological studies assessing potential human health
effects deal with exposures to extremely high levels, often orders of magni
tude greater than actual exposure. Consequently, risks at low levels are
estimated by mathematical modeling, utilizing assumptions about which
there is considerable uncertainty.
The organizing committee is committed to the enhanced understanding of
low-dose responses of all types, of an expected nature (e.g., linear, sublin-
ear) or of a so-called paradoxical nature. Paradoxical dose-response rela
tionships might include U-shaped dose-response curves, hormesis, and, in
some restrictive sense, biphasic dose-response curves. Although there are
many scattered reports of such paradoxical responses in the biomedical
literature, these responses have not been rigorously assessed, nor have the
underlying mechanisms been adequately identified. Laboratory and regula
tory scientists have tended to dismiss these paradoxical responses as curiosi
ties or anomalies inconsistent with the conventional paradigm.
The proposed activities of the BELLE committee would focus on dose-
response relationships to toxic agents, pharmaceuticals, and natural prod
ucts studied over wide dosage ranges in in vitro systems and in vivo systems,
including human populations. The initial goal of BELLE is the scientific
evaluation of the existing literature and of ways to improve research and
assessment methods. While the principal emphasis of the committee is to
promote an assessment of the scientific foundations of BELLE, the need to
assess the regulatory implications of BELLE is recognized and will be incor
porated in BELLE activities.
The Advisory Committee (pp. ix-xi) authorized Professor Edward J.
Calabrese, School of Public Health, University of Massachusetts, Amherst,
to organize a workshop on current knowledge about BELLE, with particu
lar emphasis on the toxicological implications of biological adaptations.
This meeting was held on April 30 and May 1, 1991, at the University of
Massachusetts. The meeting was designed to help establish a scientific base
for future BELLE initiatives. The meeting was attended by the seven invited
speakers, the BELLE Advisory Committee, and a number of invited guests
from universities, federal agencies, and private sector organizations.
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