Abstract:
:Highly standardized and controlled inhalation studies are required for hazard identification to make test results reproducible and comparable and to fulfill general regulatory requirements for the registration of new drugs, pesticides, or chemicals. Despite significant efforts, the results of inhalation studies have to be analyzed judiciously due to the great number of variables. These variables may be related to technical issues or to the specific features of the animal model. Although inhalation exposure of animals mimics human exposure best, ie, error-prone route-to-route extrapolations are not necessary, not all results obtained under such very rigorous test conditions may necessarily also occur under real-life exposure conditions. Attempts are often made to duplicate as closely as possible these real-life exposure conditions of humans in appropriate bioassays. However, this in turn might affect established baseline data, rendering the interpretation of new findings difficult. In addition, specific use patterns, eg, of inhalation pharmaceuticals or pesticide-containing consumer products, may impose test agent-specific constraints that challenge traditional approaches. Moreover, specific modes of action of the substance under investigation, the evaluation of specific endpoints, or the clarification of equivocal findings in common rodent species may require exposure paradigms or the use of animal species not commonly used in inhalation toxicology. However, particularly in inhalation toxicology, the choice of animal models for inhalation toxicity testing is usually based on guideline requirements and practical considerations, such as exposure technology, expediency, and previous experience rather than validity for use in human beings. Larger animal species, apart from the welfare aspects, may require larger inhalation chambers to accommodate the animals, but for technical reasons and the difficulty of generating homogeneous exposure atmospheres in such inhalation chambers, this may jeopardize the outcome of the study. Some of the many variables and possible artifacts likely to occur in animal inhalation studies are addressed in this paper.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Pauluhn J,Mohr Udoi
10.1177/019262330002800514subject
Has Abstractpub_date
2000-09-01 00:00:00pages
734-53issue
5eissn
0192-6233issn
1533-1601journal_volume
28pub_type
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