A retrospective review of the carcinogenicity of refractory ceramic fiber in two chronic Fischer 344 rat inhalation studies: An assessment of the MTDand implications for risk assessment

The purpose of this article is to review previous chronic inhalation studie s in rats with refractory ceramic fiber (RCF), the mathematical modeling ef forts to describe the deposition, clearance, and retention of RCF fiber in the rat and human, and the concept of "overload," and to assess the possibi lity that the maximum tolerated dose (MTD) was exceeded, lastly, based on r ecent biopersistence and pulmonary clearance studies of several investigato rs with a particulate-free RCF, we examine the potential impact on the chro nic RCF rat bioassay of coexposure to both RCF particulate and RCF fibers. The review concludes, inter alia, that RCF particulate coexposure probably had a major impact on the observed chronic adverse effects, that the MTD wa s probably exceeded at the highest exposure concentration of 30 mg/m(3) in the rat bioassay, and that inclusion of the highest dose in the risk assess ment process may overstate human health risk if a linear rather than nonlin ear model is used.