28-Day (Subacute) Inhalation Toxicity Study (OECD TG 412)

Abstract

882. This assay determines the subchronic inhalation toxicity of chemicals to provide data for quantitative inhalational hazard identification/characterisation. It is primarily used to derive regulatory concentrations for assessing worker risk in occupational settings. It may also be used to assess human residential, transportation and environmental risk. Dosing duration is 28 days and the preferred species is the rat. Animals are exposed to test substance in inhalation chambers for six hours per day on a five day per week basis. The preferred mode of exposure is nose only, but whole body exposure may also be used. OECD TG 412 was first adopted in 1981, revised in 2009 and 2017. Although it has not been validated for the detection of endocrine active substances (EASs), this assay contains several endpoints that are suitable for the determination of endocrine effects. As all the endpoints are apical, it is difficult to discern mechanism of action from this test alone. Information on mechanism of action may need to be obtained from in vitro estrogen/androgen/thyroid/steroidogenesis (E,A,T,S) assays or in vivo lower tier tests such as the Uterotrophic Bioassay (UT – OECD TG 440) and the Hershberger Bioassay (H – OECD TG 441). Hormone measurements are not included in this assay.