title: Acute inhalation toxicity testing: considerations of technical and regulatory aspects.
abstract: The EU regulatory statute for the acute hazard identification of chemicals requires selection of the two most appropriate routes of administration. Testing employing the oral route is mandatory, whereas selection of the dermal or inhalation route requires expert judgement, i.e. considerations of structural alerts with regard to the inherent acute inhalation toxicity as well as the likelihood of dermal and inhalation exposure, respectively. Currently, testing of chemicals requires acute inhalation exposure of 4-h and 1-h durations according the EU classification and labelling and UN Transport Guidelines, respectively. The analysis made revealed that 1-h exposures appear to add little knowledge in addition to existing 4-h LC50 values and a default value of 4 should be used for conversion of 4-h to 1-h LC50 values, independently of the physical state of the chemical. Therefore, also the unit of concentration of exposure atmospheres should be independent of nominal features of the test substance. Hence, the preferred dose metric is mass (mg/liter air) rather than volume (ppm). Taking into account the overall variability of acute toxicity data the recommendations given are classification into the following groups of 4-h LC50 values: < or = 0.05, > 0.05-0.2, > 0.2-1, > 1-5 and > 5.0 mg/l. No distinction should be made concerning vapours and aerosols with regard to units and conversion factors from 4-h to 1-h LC50 values and the default factor of 4 appears to be most suitable. Further differentiation of classification is not indicated due to technical variability of acute inhalation testing and resolution of the acute bioassay.
authors.affiliation: Bayer AG, Institut für Toxikologie, Wuppertal, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Pauluhn
authors.forename: D
authors.initials: D
authors.lastname: Bury
authors.forename: U
authors.initials: U
authors.lastname: Föst
authors.forename: A
authors.initials: A
authors.lastname: Gamer
authors.forename: E
authors.initials: E
authors.lastname: Hoernicke
authors.forename: T
authors.initials: T
authors.lastname: Hofmann
authors.forename: M
authors.initials: M
authors.lastname: Kunde
authors.forename: T
authors.initials: T
authors.lastname: Neustadt
authors.forename: E
authors.initials: E
authors.lastname: Schlede
authors.forename: H
authors.initials: H
authors.lastname: Schnierle
authors.forename: K
authors.initials: K
authors.lastname: Wettig
authors.forename: D
authors.initials: D
authors.lastname: Westphal
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D005062:European Union; D007928:Lethal Dose 50; D004364:Pharmaceutical Preparations / Q000145:classification; D018675:Toxicity Tests / Q000379:methods*; D014116:Toxicology / Q000331:legislation & jurisprudence*
chemical_list: D004364:Pharmaceutical Preparations