NASAL TISSUE DOSIMETRY?ISSUES AND APPROACHES FOR "CATEGORY 1" GASES: A Report on a Meeting Held in Research Triangle Park, NC, February 11?12, 1998

Abstract

Three organizations, the Basic Acrylic Monomer Manufacturers (BAMM), Methacrylate Producers Association (MPA), and Vinyl Acetate Toxicology Group (VATG), have sponsored development of physiologically based pharmacokinetic (PBPK) models for nasal tissue dosimetry with, respectively, acrylic acid (AA), methyl methacrylate (MMA), and vinyl acetate (VA). These compounds cause lesions in nasal epithelial tissues and are classified as "Category 1" gases within the U.S. EPA (1994) classification scheme. The National Center for Environmental Assessment in the U.S. EPA Office of Research and Development also has continuing interests in refining its methods for dosimetry adjustments when data on mode of action are available for Category 1 gases. A round-table discussion was held in Research Triangle Park, NC, on 11-12 February 1998, to develop a broader appreciation of the key processes and parameters required in developing nasal tissue dosimetry models. The discussions at the round table drew on these three case studies and several background presentations to assess the manner in which chemical-specific and mode-of-action data can be incorporated into nasal dosimetry models. The round table had representation from the U.S. EPA, academia, and industry. This article outlines the presentations and topical areas discussed at the round table and notes recommendations made by participants to extend models for nasal dosimetry and to develop improved data for modeling. The contributions of several disciplines ? toxicology, engineering, and physiologically based pharmacokinetic (PBPK) modeling ? were evident in the discussions. The integration of these disciplines in creating opportunities for dosimetry model applications in risk assessments has several advantages in the breadth of skills upon which to draw in model development. A disadvantage is in the need to provide venues and develop cross-discipline dialogue necessary to ensure the understanding of cultural attitudes, terminology, and methods. The round-table discussions were fruitful in achieving such enhanced understanding and communication. Subsequent elaboration of these models will benefit from the interactions of these groups at the round table. The round-table discussions have already led to model improvements ? as noted in several recently published articles. Participants emphasized several generic data needs in relation to nasal vapor uptake studies in human subjects, to broader discussion of tissue diffusion models, and to extensions to other classes of gases. The round-table articles that are published separately in this issue and the discussions, captured in this overview, provide a glimpse of the state of the science in nasal dosimetry modeling and a clear indication of the growth of and continuing opportunities in this important research area.