Environmental Health Perspectives 105, Supplement 5, September 1997

[ Citation in PubMed ] [ Related Articles ]

Relevance of Particle-induced Rat Lung Tumors for Assessing Lung Carcinogenic Hazard and Human Lung Cancer Risk

Joe L. Mauderly

Lovelace Respiratory Research Institute, Albuquerque, New Mexico

Abstract
Rats and other rodents are exposed by inhalation to identify agents that might present hazards for lung cancer in humans exposed by inhalation. In some cases, the results are used in attempts to develop quantitative estimates of human lung cancer risk. This report reviews evidence for the usefulness of the rat for evaluation of lung cancer hazards from inhaled particles. With the exception of nickel sulfate, particulate agents thought to be human lung carcinogens cause lung tumors in rats exposed by inhalation. The rat is more sensitive to carcinogenesis from nonfibrous particles than mice or Syrian hamsters, which have both produced false negatives. However, rats differ from mice and nonhuman primates in both the pattern of particle retention in the lung and alveolar epithelial hyperplastic responses to chronic particle exposure. Present evidence warrants caution in extrapolation from the lung tumor response of rats to inhaled particles to human lung cancer hazard, and there is considerable uncertainty in estimating unit risks for humans from rat data. It seems appropriate to continue using rats in inhalation carcinogenesis assays of inhaled particles, but the upper limit of exposure concentrations must be set carefully to avoid false-positive results. A positive finding in both rats and mice would give greater confidence that an agent presents a carcinogenic hazard to man, and both rats and mice should be used if the agent is a gas or vapor. There is little justification for including Syrian hamsters in assays of the intrapulmonary carcinogenicity of inhaled agents. -- Environ Health Perspect 105(Suppl 5):1337-1346 (1997)

Key words : cancer, lung, inhalation, rat, mouse, hamster, particles, pollution, fibers

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 10 July 1997.

The author appreciates the contributions and comments of F.F. Hahn, K.J. Nikula, and M.B. Snipes, and the technical editing of P. Bradley, all of Lovelace Respiratory Research Institute. This review was supported by the U.S. Department of Energy under contract DE-AC04-76EV01013.

Address correspondence to Dr. J.L. Mauderly, Lovelace Respiratory Research Institute, 2425 Ridgecrest SE, Albuquerque, NM 87108. Telephone: (505) 262-7938. Fax: (505) 262-7043. E-mail: jmauderl@lrri.org

Abbreviations used: IARC, International Agency for Research on Cancer; NTP, U.S. National Toxicology Program.

[ Table of Contents ] [ Full Article ] [ Citation in PubMed ] [ Related Articles ]

Last Update: November 28, 1997