Monday, April 13, 2009

An Early Version of the Particle Overload Houdini Hypothesis

Toxicology and Applied Pharmacology
Volume 99, Issue 3, July 1989, Pages 377-383

Contemporary issue in toxicology

Establishing aerosol exposure concentrations for inhalation toxicity studies

Trent R. Lewis*, Paul E. Morrow, Roger O. McClellan, Otto G. Raabe§, Gerald L. Kennedyshort parallel, Bernard A. Schwetzperpendicular, Thomas J. Goehlperpendicular, Joseph H. Roycroftperpendicular and Rajendra S. Chhabraperpendicular

* Division of Biomedical and Behavioral Science, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, Ohio 452276, USA

Environmental Health Science Center, University of Rochester, Rochester, NY 14642, USA

Lovelace Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185, USA

§ Laboratory for Energy-Related Health Research, University of California, Davis, California 95616, USA

short parallel Haskell Laboratory, E.I. duPont de Nemours & Co., Newark, Delaware 19711, USA

perpendicular National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA

Received 15 October 1988;
accepted 28 March 1989.
Available online 27 September 2004.


Criteria for the selection of aerosol concentrations to be used in inhalation studies assessing the toxicity and carcinogenicity of chemical substances were discussed by the authors in a meeting sponsored by the National Toxicology Program. Concepts in the design of aerosol inhalation studies emerged from that meeting and are being communicated through this publication. Inhalation studies assessing the toxicity and carcinogenicity of aerosols have often used maximum exposure levels on the basis of technological feasibility. Evidence has now accumulated that the amount of pulmonary burden of deposited particles impacts on particle clearance above some as yet not well-defined exposure concentration. The sequelae are such that lung clearance decreases with increased particulate burden to the point of approaching complete cessation. This paper focuses on the major determinants in establishing maximal aerosol concentrations for use in inhalation toxicity studies with special emphasis on experimental design features to assess lung retention. The subject matter of this paper is a rapidly developing area in terms of knowledge. Accordingly, the contents of this article are intended as guidelines and not as absolute rules for the conduct and interpretation of inhalation exposure studies

BrooklynDodger(s) comment: The problem with the pulmonary overload reduced lung clearance Houdini risk assessment hypothesis, is that something not cleared is causing lung tumors. In a single agent study, the agent would have to prevent its own clearance, although there are likely other conditions which would reduce clearance in a human population. So this is a potency issue, not a toxic potential issue. Although, since the negative control, titanium dioxide, is now carcinogenic, it appears that any old particulate material will cause lung tumors. The Dodger(s) note(s) that Roger McClellen co-authored this from Lovelace, an institution of the DOE, before he left to head CIIT.

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