This revised Test Guideline 412 (TG 412) has been designed to fully characterize test
article toxicity by the inhalation route following repeated exposure for a limited
period of time (28 days), and to provide data for quantitative inhalation risk assessments.
It was updated in 2017 to enable the testing and characterisation of effects of nanomaterials
tested.Groups of at least 5 male and 5 female rodents are exposed 6 hours per day
for 28 days to a) the test chemical at three or more concentration levels, b) filtered
air (negative control), and/or c) the vehicle (vehicle control). Animals are generally
exposed 5 days per week but exposure for 7 days per week is also allowed. Males and
females are always tested, but they may be exposed at different concentration levels
if it is known that one sex is more susceptible to a given test article. This guideline
allows the study director the flexibility to include satellite (reversibility) groups,
bronchoalveolar lavage (BAL), lung burden (LB) for particles, neurologic tests, and
additional clinical pathology and histopathological evaluations in order to better
characterize the toxicity of a test chemical.