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DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY
Citation:
Slikker, W., M. E. Andersen, M. S. Bogdanffy, J. S. Bus, S. Cohen, R. B. Conolly, R. M. David, N. G. Doerrer, D. C. Dorman, D. W. Gaylor, D. B. Hattis, J M. Rogers, R W. Setzer, J. A. Swenberg, AND K. B. Wallace. DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL, 201(3):226-94, (2004).
Impact/Purpose:
This paper addresses the issues discussed at two workshops, and presents the consensus conclusions drawn by expert participants related to dose-dependent transitions in mechanisms of toxicity
Description:
Scientists and decision-makers from all sectors agree that risk assessments should be
based on the best available science. Several years ago, the Health and Environmental
Sciences Institute (HESI), a global branch of the International Life Sciences Institute
(ILSI), identified the need for better scientific understanding of dose-dependent
transitions in mechanisms of toxicity as one avenue by which the best and latest science
can be integrated into the decision-making process. In July 2001, the HESI Project
Committee on Dose-Dependent Transitions in Mechanisms of Toxicity established a
group of academic, government, and industry scientists to engage in active technical
discourse on the issue of dose-dependent transitions in mechanisms of toxicity. Over
the next 18 months, case studies were examined. These case studies included
acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene
chloride, the peroxisome proliferator-activated receptor, progesterone/hydroxyflutamide,
propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc (Slikker et al.,
2004).
The HESI Project Committee sponsored two technical workshops in 2003. The first of
these workshops took place on February 12-13, 2003, and was co-sponsored by the
Agency for Toxic Substances and Disease Registry, the American Chemistry Council,
the National Institute of Environmental Health Sciences, the Society of Toxicology, and
the US Environmental Protection Agency. Additional support was provided by Health
Canada. Invited experts from government, academia, and industry provided scientific
perspectives and recommendations at the workshop. The purpose of the workshop was
to examine approaches to dose-response analysis, learn from the case study examples,
and gather feedback from invited participants on the impact of dose-dependent
transitions on the risk assessment process. The second forum consisted of a workshop
in March 2003 at the Society of Toxicology Annual Meeting in Salt Lake City, UT. This
paper addresses the issues discussed at both workshops, and presents the consensus
conclusions drawn by expert participants.