acute inhalation toxicity

/Tag:acute inhalation toxicity

Estimation of the Acute Inhalation Hazards of Chemicals Based on Route-to-route and Local Endpoint Extrapolation: Experience from Bulk Maritime Transport

Thomas Höfer, Derek James, Tore Syversen and Tim Bowmer

Data on acute lethal inhalation toxicity from animal studies are commonly required for assessing the hazards to human health of volatile, gaseous and dusty chemicals or their mixtures. The International Maritime Organisation (IMO) made the provision of acute inhalation toxicity data a mandatory requirement for the carriage of bulk liquid chemicals transported by sea in tank ships, thereby creating the need for inhalation data on many hundreds of chemicals in bulk maritime transport. Taking note of previously published proposals for estimating acute inhalation toxicity hazards for chemicals, and the paucity of measured experimental data, an extrapolation method has been developed by the Group of Experts on the Scientific Aspects of Marine Environmental Protection (GESAMP) to partly fulfil this need. This method should be seen as a pragmatic approach to the challenge of missing measured experimental test data, with the added benefit of reducing tests in experimental animals. The method is based on a route-to-route (i.e. between-route) extrapolation of information on acute oral and/or dermal toxicity, in combination with data on the potential for irritation and/or corrosion to skin and eyes. The validation of this method was based on the individual evaluation of inhalation toxicity studies for 330 chemicals, including mixtures and many important chemical groups, for which the IMO holds public and industryconfidential data. The authors contend that this extrapolation method offers a reliable basis for hazard evaluation in the context of bulk maritime transport, and the ‘GESAMP inhalation toxicity extrapolation method’ has become part of the IMO regulatory system for the carriage of bulk liquids (i.e. noxious liquid substances) on board tank ships.
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A Pilot Study on the Refinement of Acute Inhalation Toxicity Studies: The Isolated Perfused Rat Lung as a Screening Tool for Surface-active Substances

Monika Fischer, Wolfgang Koch, Horst Windt and Clemens Dasenbrock

New surface-active agents in waterproofing sprays are frequently tested for acute inhalation toxicity in vivo according to OECD Test Guideline 403. In order to refine and reduce the number of acute inhalation tests performed, we propose a screening test that uses isolated lungs. The test consists of the exposure of isolated, ventilated and perfused rat lungs, to aerosolised formulations of waterproofing agents (mass median aerodynamic diameter = 1μm), and on-line monitoring of respiratory parameters and gross pathology analysis. A pilot evaluation of the isolated perfused rat lung model for use in a screening test was carried out by blind testing 12 surface-active substances. The results obtained compared well with data available from in vivo acute inhalation studies. Substances that triggered harmful effects, such as impaired lung compliance and atelectasis of the isolated perfused lung, were also found to cause changes in respiratory parameters, some of which would be severe enough to lead to death in in vivo tests with rats. The changes in respiratory parameters suggest that the mode-of-action is associated with impairment of the surfactant layer. Therefore, pre-testing in the isolated perfused rat lung allows the identification of surface-active substances with the potential for causing acute inhalation toxicity.

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