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I I I I I I I I I I I I I I I I I I AUTHOR: PEPELKO, WILLIAM E, ~ DATE: 1984 TITLE: EXPERIMENTAL RESPIRATORY CARCINOGENSIS IN SMALL LABORATORY ANIMALS CITATION: ENVIRONMENTAL RESEARCH 33:144-188 (1984) STUDY DESIGN: This is a review which addressed the effects of inhaled chemicals, with the exception of radioactive compounds, upon induction of respiratory tract cancer in small laboratory animals. With certain chemicals, where lung tumors are not always the major endpoint, the review discussed tumors at other locations. Studies not included in this review were those in which respiratory tract tumors were induced by means other than inhalation, inhalation toxicity studies designed to address nonocogenic endpoints, or studies of such short duration that the development of lung tumors would be considered very unlikely. The contents of this review were: Introduction; Relative advantages and disadvantages of mice, rats and Syrian hamsters for use in respiratory carcinogensis; Organic chemicals; Inorganic metallic compounds; Inorganic nonmetallic compounds; Complex mixtures (including cigarette smoke); Summary and Conclusions, RNDINGS/RESULTS/CONCLUSIONS: Cancer of the respiratory tract can be induced in small laboratory animals by a wide variety of vapors, dust, and aerosols. What is less certain is how well the results predict carcinogenic potency of the test substances in humans. Of prime importance however, is the ability to extrapolate animal data to humans. Comparison of the relative carcinogenic potency of inhaled chemicals between humans and laboratory animals are usually limited by a lack of epidemiological data and/or accurate exposure assessment in humans. In most cases in which a carcinogenic effect has been detected in humans, a positive response was also found in lab animals. Positive responses in lab animals, on the other hand, are not often accompanied by similar finding in humans. One of the most likely reasons is a lack of human studies. Second, even when human studies are available, exposures may not have been at a sufficient concentration or of adequate duration to induce positive effects. Third, effects may have occurred in humans, but due to the limited size of the exposure group, deficiencies in the design or conduct of the experiment, effects were not detected. Finally, it is possible, in some instances, that humans are tess sensitive than the test animals. There are several possible reasons for variations in responsiveness between lab animals and humans. The target organs may differ in inherent sensitivity. Another important factory is the concentration of the test substance at the critical target organ. Concentrations at the target organ can be influenced by exposure patterns. Despite the limitations in the use of animal-inhalation experiments to predict the likelihood of cancer induction in humans, and despite the fact that such tests are expensive and time consuming, there are no clearcut better alternatives at present.