Experimental validation of a model for diffusion-controlled absorption of organic compounds in the trachea
- National Inst. for Working Life, Solna (Sweden)
- and others
Most chemically induced lung cancer originates in the epithelial cells in the airways. Common conceptions are that chemicals deposited on the airway surface are rapidly absorbed through mucous membranes, limited primarily by the rate of blood perfusion in the mucosa. It is also commonly thought that for chemicals to induce toxicity at the site of entry, they must be either rapidly reactive, readily metabolizable, or especially toxic to the tissues at the site of entry. For highly lipophilic toxicants, there is a third option. Our mathematical model predicts that as lipophilicity increases, chemicals partition more readily into the cellular lipid membranes and diffuse more slowly through the tissues. Therefore, absorption of very lipophilic compounds will be almost entirely limited by the rate of diffusion through the epithelium rather than by perfusion of the capillary bed in the subepithelium. We have reported on a preliminary model for absorption through mucous membranes of any substance with a lipid/aqueous partition coefficient larger than one. The purpose of this work was to experimentally validate the model in Beagle dogs. This validated model on toxicant absorption in the airway mucosa will improve risk assessment of inhaled
- Research Organization:
- Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States). Inhalation Toxicology Research Inst.
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 381358
- Report Number(s):
- ITRI-146; ON: DE96008986; CNN: Grant R01-ES05910; TRN: 96:002767-0012
- Resource Relation:
- Other Information: PBD: Dec 1995; Related Information: Is Part Of Inhalation Toxicology Research Institute. Annual report, October 1, 1994--September 30, 1995; Bice, D.E.; Hahn, F.F.; Hoover, M.D.; Neft, R.E.; Thornton-Manning, J.R.; Bradley, P.L. [eds.]; PB: 214 p.
- Country of Publication:
- United States
- Language:
- English
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