A baseline inhalation toxicity model for narcosis in mammals

• Published in: SAR and QSAR in environmental research Vol. 20; no. 5-6; pp. 567 - 578
• Main Authors: Veith, G.D., Petkova, E.P., Wallace, K.B.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Group 01.07.2009
• Subjects: Administration, Inhalation; Animals; inhalation; LC50; Lethal Dose 50; Models, Statistical; Narcotics - administration & dosage; Narcotics - toxicity; QSAR; Quantitative Structure-Activity Relationship; Rodentia; rodents; Time Factors; toxicity
• ISSN: 1062-936X; 1029-046X
• DOI: 10.1080/10629360903278669

This paper presents the results of an analysis of the rodent inhalation literature and the development of a quantitative structure-activity relationships (QSAR) model for 4-hour LC50 as baseline toxicity to complement the baseline toxicity model for aquatic animals. We used the same literature review criteria developed for the ECOTOX database which selects only primary references with explicit experimental methods to form a high-quality database. Our literature review focused on the primary references reporting a 4-hour exposure for a single species of rodent in which the chemical had been clearly tested as a vapour and for which the exposure concentrations were not ambiguous. An expert system was used to remove reactive chemicals, receptor-mediated toxicants, and any test that produced symptoms inconsistent with non-polar narcosis. The QSAR model derived for narcosis in rodents was log LC50 = 0.69 × log VP + 1.54 which had an r 2 of 0.91, which is significantly better than the baseline toxicity model for aquatic animals. This simple model suggests that there is no intrinsic barrier to estimating baseline toxicity for in vivo endpoints in mammalian or terrestrial toxicology.