CHRONIC INHALATION TOXICITY AND CARCINOGENICITY TESTING OF RESPIRABLEFIBROUS PARTICLES

On May 8-10, 1995, a workshop on chronic inhalation toxicity and carci nogenicity testing of respirable fibrous particles was held in Chapel Hill, North Carolina, The workshop was sponsored by the Office of Poll ution Prevention and Toxics, U.S. Environmental Protection Agency (EPA ), in collaboration with the National institute of Environmental Healt h Sciences (NIEHS), the National Institute for Occupational Safety and Health (NIOSH), and the Occupational Safety and Health Administration (OSHA). The goal of the workshop was to obtain input from the scienti fic community on a number of issues related to fiber testing. Major is sues for discussion were: (i) the optimal design and conduct of studie s of the health effects of chronic inhalation exposure of animals to f ibers; (ii) preliminary studies which would be useful guides in design ing the chronic exposure study; (iii) mechanistic studies which would be important adjuncts to the chronic exposure study to enable better i nterpretation of study results and extrapolation of potential effects in exposed humans; and (iv) available screening tests which can be use d to develop a minimum data set for (a) making decisions about the pot ential health hazard of the fibers and (b) prioritizing the need for f urther testing in a chronic inhalation study. After extensive discussi on and debate of the workshop issues, the general consensus of the exp ert panel is that chronic inhalation studies of fibers in the rat are the most appropriate tests for predicting inhalation hazard and risk o f fibers to humans. A number of guidances specific for the design and conduct of prechronic and chronic inhalation studies of fibers in rode nts were recommended, For instance, it was recommended that along with other information (decrease in body weight, systemic toxicity, etc.), data should be obtained on lung burdens and bronchoalveolar lavage fl uid analysis to assist in establishing the chronic exposure levels, Lu ng burden data are also important for quantifying aspects of risk asse ssment related to dosimetric adjustments before extrapolation. Althoug h mechanistic studies are not recommended as part of the standard chro nic inhalation studies, the expert panel stressed the need for obtaini ng mechanistic information as far as possible during the course of sub chronic or chronic inhalation studies. At present, no single assay and battery of short-term assays can predict the outcome of a chronic inh alation bioassay with respect to carcinogenic effects. Meanwhile, seve ral short-term in vitro and in vivo studies that may be useful to asse ss the relative potential of fibrous substances to cause lung toxicity /carcinogenicity have been identified. (C) 1996 Academic Press, Inc.