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 assessment of the biological effects of low
level exposures (BELLE) to chemical agents and
radioactivity. The meeting was convened because of the
recognition that most human exposures to chemical and
physical agents are at relatively low levels, yet most
toxicological studies assessing potential human health
effects involve exposures to quite high levels, often orders
of magnitude greater than actual human exposures.
Consequently, risks at low levels are estimated by various
means, frequently utilizing assumptions about which there
may be considerable uncertainty.
The (BELLE) Advisory Committee is committed to the enhanced
understanding of low-dose responses of all types, whether of
an expected nature (e.g., linear, sublinear) or of a
so-called paradoxical nature. Paradoxical dose-response
relationships 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 have not generally been rigorously
assessed, nor have the underlying mechanisms been adequately
identified. Laboratory and regulatory scientists have tended
to dismiss these paradoxical responses as anomalies
inconsistent with conventional scientific paradigms.
The focus of BELLE encompasses dose-response relationships
to toxic agents, pharmaceuticals, and natural products over
wide dosage ranges in in vitro, and in vivo
systems, including human populations. While a principal
emphasis of BELLE is to promote the scientific understanding
of low-level effects (especially seemingly paradoxical
effects), the initial goal of BELLE is the scientific
evaluation of the existing literature and of ways to improve
research and assessment methods.
The BELLE Advisory Committee authorized Professor Edward J.
Calabrese, School of Public Health, University of
Massachusetts, Amherst, to organize a workshop on current
knowledge relevant to BELLE, with particular 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 intended to
help establish a basis for future BELLE initiatives and was
attended by seven invited speakers, the BELLE Advisory
Committee, and a number of invited guests from universities,
federal agencies, and private sector organizations. The
proceedings ("Biological Effects of Low Level Exposures to
Chemicals and Radiation"), were published (Lewis Publishers,
This workshop provided an important benchmark for future
BELLE activities. The presentations indicated that the
biological systems have an impressive array of adaptations
that may be turned on in response to various stresses,
including physiological stress, as well as exposure to
radiation, toxic chemicals, and dietary alterations. Despite
the striking findings of some of the presentations, such as
that by Hart and colleagues that DNA repair efficiency and
fidelity are markedly enhanced in caloric restricted diets,
the implications of these findings for human populations
remains to be further investigated and established.
Nonetheless, this publication of the BELLE program provided
the first of what is planned to be a series of carefully
coordinated and focused reports that will clarify the
biological effects of low level exposures to chemical and
physical agents on biological systems and human populations.