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Refinement of acute inhalation toxicity studies: The isolated perfused rat lung as a screening tool for surface-active substances

: Dasenbrock, Clemens; Fischer, Monika; Windt, Horst; Koch, Wolfgang

The Toxicologist 53 (2014), Nr.1, S.324, PS 1226
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <53, 2014, Phoenix/Ariz.>
Fraunhofer ITEM ()

New surface-active agents in waterproofing sprays are often tested for acute inhalation toxicity in vivo on the basis of OECD Test Guideline 403. A screening test using the isolated perfused rat lung (IPRL) is proposed in order to reduce the number of acute inhalation tests and to refine these. The test comprises exposure of IPRLs to aerosolised formulations of the water proofing agents and on-line monitoring of respiratory parameters.
Substances revealing harmful effects on the IPRL, such as impaired lung compliance and atelectasis formation, did also show changes in respiratory parameters up to mortality in in vivo tests with rats. Thus, pre-testing in the IPRL allows the identification of surface-active substances causing acute inhalation toxicity. To assess the potential lung toxicity of seven formulations, each tested in two male and two female IPRLs, we evaluated changes in the respiratory parameters tidal volume, compliance, and resistance, edema and atelectasis formation, taking into account the inhaled doses. These IPRL results were compared with available in vivo results and a good or excellent correlation in six out of seven cases was revealed. In conclusion, the use of the IPRL is well suited for screening substances showing acute "physical" inhalation toxicity. Therefore, for future assessment of surface active substances, it is suggested to use this test prior to in vivo inhalation tests. Formulations with no acute harmful effects on the IPRL need to be further investigated in vivo for complete risk assessment. However, substances showing strong reactions in the IPRL will most likely cause lung damage in vivo. This is why testing in live animals is not recommended in order to avoid possible pain, suffering or distress.