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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, 1992).

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.





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