ToxStrategies’ scientists Camarie Perry, Stephanie Vivanco, Ann Holbrow Verwiel, and Deborah Proctor conducted a regulatory and scientific literature review to develop an acute/short-term inhalation guideline for manganese in ambient air, protective of respiratory effects and neurotoxicity. To reduce uncertainty regarding manganese accumulation in the brain from short-term exposures, the authors used previously published physiologically-based pharmacokinetic (PBPK) modelling to support that the derived 24-h inhalation guideline of 5 μg/m3 is protective for sensitive life-stages. As very few short-term exposure guidelines have been established, this guideline provides new information for use in air toxics risk assessment.