Extrapolation of Inhaled Particulate Toxicity Data from Experimental Animals to Humans
Abstract
Significant progress has been made over the past three years to develop methodology and assess various tissues and tissue sensitivity endpoints with the ultimate goal of validating a proposed extrapolation model. This model will allow the quantitative extrapolation of inhaled particulate toxicology data from experimental animals to man. Methodology was developed to accurately measure nucleotide levels in small tissue samples, to determine cellular toxicant levels, to isolate tissue or cells at various levels of the respiratory tract, and to culture animal and human cells for identical treatment conditions. The tissues assessed were nasal turbinate epithelial, olfactory epithelial, and alveolar macrophages. Nasal and pulmonary lavage fluids were also studied. These comprehensive, comparative animal to human extrapolation studies were unique in that, for the first time, tissue response was measured as a function of actual cellular dose, and common endpoints were used for the same target cell types in different species. The described cell sensitivity model could then be used to provide quantitative animal to human extrapolation values for inhaled particulates, which will be extremely valuable for human risk assessment. Keywords: Models; Risk assessment; Toxicity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 1988
- Accession Number
- ADA201994
Entities
People
- Daniel L. Morgan
- Gary E. Hatch
- Vernon E. Steele
Organizations
- Environmental Protection Agency