title: A retrospective review of the carcinogenicity of refractory ceramic fiber in two chronic fischer 344 rat inhalation studies: an assessment of the MTD and implications for risk assessment.
abstract: The purpose of this article is to review previous chronic inhalation studies in rats with refractory ceramic fiber (RCF), the mathematical modeling efforts to describe the deposition, clearance, and retention of RCF fiber in the rat and human, and the concept of "overload," and to assess the possibility that the maximum tolerated dose (MTD) was exceeded. Lastly, based on recent biopersistence and pulmonary clearance studies of several investigators with a particulate-free RCF, we examine the potential impact on the chronic 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 was 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 assessment process may overstate human health risk if a linear rather than nonlinear model is used.
authors: Everest Consulting Associates, 15 North Main Street, Cranbury, NJ 08512-3203, USA. rwmast@email.msn.com
authors: R W
authors: RW
authors: Mast
authors: C P
authors: CP
authors: Yu
authors: G
authors: G
authors: Oberdörster
authors: E E
authors: EE
authors: McConnell
authors: M J
authors: MJ
authors: Utell
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001822:Body Burden; D002516:Ceramics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004391:Dust / Q000009:adverse effects; D005898:Glass; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008452:Maximum Allowable Concentration; D008657:Metabolic Clearance Rate; D009374:Neoplasms, Experimental / Q000209:etiology*; D016273:Occupational Exposure; D051381:Rats; D011916:Rats, Inbred F344; D012189:Retrospective Studies; D018570:Risk Assessment
chemical_list: D004391:Dust; C009753:fiberglass