Review Article: Inhalation Studies in Laboratory Animals—Current Concepts and Alternatives

Pauluhn, Jürgen; Möhr, U.

doi:10.1177/019262330002800514

Cited by 82 publications

(35 citation statements)

References 65 publications

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“…Neither the acute 8 h exposure of rats nor the 1 h sensory irritation study in mice and rats provided experimental evidence that irritant particlerelated effects had occurred in the lower respiratory tract to any appreciable extent. The reflexively induced hypothermia observed in rats is a typical finding in rats exposed to upper respiratory tract irritants (Pauluhn and Mohr, 2000). The maximum level of COHb of ≈40% was recorded after an 8 h whole-body exposure to a timeweighted average concentration of approximately 300 ppm CO (TSP 27 mg m −3…”

Section: Discussionmentioning

confidence: 95%

Mosquito coil smoke inhalation toxicity. Part I: Validation of test approach and acute inhalation toxicity

Pauluhn

2006

J. Appl. Toxicol.

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Burning mosquito coils indoors to repel mosquitoes is a common practice in many households in tropical countries. The evaluation and assessment of the inhalation toxicity of smoke emitted from mosquito coils appear to be particularly challenging due to the complex nature of this type of exposure atmosphere. The potential health implications of the gases, volatile agents and particulate matter emitted from burning coils or incense have frequently been addressed; however, state-of-the-art inhalation toxicity studies are scarce. The focus of this paper was comparatively to evaluate and assess the appropriateness and practical constraints of the whole-body versus the nose-only mode of exposure for inhalation toxicity studies with burning mosquito coils. With regard to the controlled exposure of laboratory animals to complex smoke atmospheres the nose-only mode of exposure had distinct advantages over the whole-body exposure, which included a rapid attainment of the inhalation chamber steady state, minimization of particle coagulation and uncontrolled adsorption of condensate onto the chamber surfaces. While in whole-body chambers a different kinetic behaviour of volatile and particulate constituents was found which caused inhomogeneous, i.e. artificially enriched atmospheres with volatile components at the expense of aerosols, the nose-only mode of exposure provided maximum exposure intensities without losses of the particulate phase of the exposure atmosphere. Collectively, the results obtained support the conclusion that the dynamic nose-only mode of exposure is experimentally superior to the quasistatic whole-body exposure mode which provides the least control over exposure atmospheres and the outcome highly contingent on selected experimental factors. Acute inhalation toxicity studies in rats suggest that the most critical metrics of exposure are apparently related to (semi)volatile upper respiratory tract sensory irritants, whilst the asphyxic component, carbon monoxide, plays a role only at overtly irritant exposure levels. However, this study was conducted at exposure concentrations much higher than encountered by people in residential settings and the effects observed under these conditions may not be relevant to hazards from exposures at common use levels. Neither an acute 8 h exposure of rats nor the 1 h sensory irritation study in mice and rats provided experimental evidence that irritant particle-related effects had occurred in the lower respiratory tract. In summary, the protocols devised evaluate and assess the acute inhalation toxicity of mosquito coil smoke demonstrating that the nose-only mode of exposure of rats to the smoke of mosquito coils is suitable to assess the toxic potency of different coils. The nose-only mode has clear advantages over the whole-body exposure mode. The inhalation studies conducted show unequivocally that acute toxic effects are difficult to produce with this type of product even under rigorous testing conditions.

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Section: Discussionmentioning

confidence: 95%

Mosquito coil smoke inhalation toxicity. Part I: Validation of test approach and acute inhalation toxicity

Pauluhn

2006

J. Appl. Toxicol.

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“…Choice of animal species is equally important for toxicological as pharmacological testing and the choice of animal models for inhalation toxicity testing is influenced by a number of factors including guideline requirements and practical considerations, such as exposure technology, expediency, previous experience [165] and differences in biological responses. Different species having different biological responses as exemplified by the varied reactions of monkeys and dogs to isoniazid outlined in section 2.2. and this impacts on the relevance of extrapolation of toxicity data to humans.…”

Section: Inhalation Toxicology In Animalsmentioning

confidence: 99%

In vivo animal models for drug delivery across the lung mucosal barrier☆

Cryan

Sivadas

García-Contreras

2007

Advanced Drug Delivery Reviews

128

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“…Acute inhalation toxicity testing guidelines and available technologies have improved significantly over time, both in terms of well defined animal exposure and test atmosphere characterization (Cheng and Moss, 1995;Dorato and Wolff, 1991;Phalen, 1984;Pauluhn and Mohr, 2000;Pauluhn, 2003;. Especially for short(er)-term inhalation studies, exposure paradigms have shifted from whole-body to nose-only modes with novel procedures to minimize the rebreathing of atmospheres, the attainment of faster inhalation chamber concentration equilibria, and optimized uniformity or degree of dynamic mixing of flows within an inhalation chamber.…”

Section: Introductionmentioning

confidence: 99%

A simple approach to validation of directed‐flow nose‐only inhalation chambers

Pauluhn

Thiel

2007

J of Applied Toxicology

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Directed-flow nose-only exposure systems are designed and operated so that the genuine test atmosphere is dynamically delivered to each exposure port and exhaled air from exposed animals is immediately exhausted without the possibility of other animals rebreathing this atmosphere. This technique is particularly useful for preventing uncontrolled changes of exposure atmospheres, stimulating breathing activity due to the rebreathing of exhaled carbon dioxide, and the conserving a test material that is available only in limited quantities. The intricate relationship of the delivered flow of air at each exposure port relative to the respiratory minute volume of the exposed animal appears to be critical for the state-of-the-art performance of directed-flow nose-only exposure systems. This analysis revealed that the determination of carbon dioxide concentrations at different inhalation chamber locations, including exposure ports, is a simple and cost-effective procedure to evaluate whether the rebreathing of atmospheres can be excluded. It has been shown that directed-flow systems need to be operated at an exposure air flow rate greater than 2.5 times the respiratory minute volume of the exposed animal or optimally approximately 0.75 l min(-1) per rat exposure port ( approximately 3.75 times the minute volume of young adult rats) to prevent higher CO(2)-concentrations occurring.

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Review Article: Inhalation Studies in Laboratory Animals—Current Concepts and Alternatives

Abstract: About the AuthorsJfrgen Pauluhn received his doctoral degree in physical chemistry (subsidiary subject pharmacology) in 1979 from the University of Freiburg (Germany). After

Cited by 82 publications

References 65 publications

Mosquito coil smoke inhalation toxicity. Part I: Validation of test approach and acute inhalation toxicity

Mosquito coil smoke inhalation toxicity. Part I: Validation of test approach and acute inhalation toxicity

In vivo animal models for drug delivery across the lung mucosal barrier☆

A simple approach to validation of directed‐flow nose‐only inhalation chambers

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