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

Three organizations, the Basic Acrylic Monomer Manufacturers (BAMM), Methac rylate Producers Association (MPA), and Vinyl Acetate Toxicology Group (VAT G), have sponsored development of physiologically based pharmacokinetic (PB PK) 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" gase s within the U.S. EPA (1994) classification scheme. The National Center for Environmental Assessment in the U.S. EPA Office of Research and Developmen t also has continuing interests in refining its methods for dosimetry adjus tments when data on mode of action are available for Category 1 gases. A ro und-table discussion was held in Research Triangle Park, NC, on 11-12 Febru ary 1998, to develop a broader appreciation of the key processes and parame ters 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-a ction 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 ext end models for nasal dosimetry and to develop improved data for modeling. The contributions of s everal disciplines-toxicology, engineering, and physiologically based pharm acokinetic ( PBPK) modeling-were evident in the discussions. The integratio n of these disciplines in creating opportunities for dosimetry model applic ations 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 p rovide venues and develop cross-discipline dialogue necessary to ensure the understanding of cultural attitudes, terminology, and methods. The round-t able discussions were fruitful in achieving such enhanced understanding and communication. Subsequent elaboration of these models will benefit from th e interactions of these groups at the round table. The round-table discussi ons have already led to model improvements-as noted in several recently pub lished articles. Participants emphasized several generic data needs in rela tion to nasal vapor uptake studies in human subjects, to broader discussion of tissue diffusion models, and to extensions to other classes of gases. T he 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 growt h of and continuing opportunities in this important research area.