Background and Purpose: As an essential element, manganese (Mn) absorption, tissue storage and excretion are controlled through homeostasis; however, upon high level exposure, Mn is known to accumulate in brain tissues and cause oxidative stress and neurological effects. As the toxicokinetics of Mn are non-linear, derivation of toxicity criteria has been challenging, and acute environmental guidelines for use in air toxics risk assessment are generally lacking. We sought to develop a 24-hour acute guideline that is protective of sensitive health outcomes including respiratory effects and neurotoxicity. Because limited toxicological and epidemiological data exist to develop such a guideline and because of concern for exposure among sensitive life stages, we used previously published physiologically-based pharmacokinetic (PBPK) models to address uncertainty regarding the potential for Mn accumulation in the globus pallidus of the brain at the proposed acute guideline. Methods: We reviewed available US state, federal, and international occupational exposure limits as well as health-based environmental inhalation toxicity criteria applicable to the general public, and their scientific bases. We then conducted a literature search of relevant publications (2005-2022) to capture more recent studies. Based on this literature review, we identified points of departure and applied appropriate uncertainty factors to determine a proposed 24-hour acute guideline. Exposures at the proposed guideline were evaluated using published PBPK models developed for male and female infants, children, and adults, ages 6 months to 60 years (Yoon et al., 2019) and using the more recent transporter model for ages 3-60 years (Campbell et al. 2022). Using the PBPK models, potential exposures were evaluated for two short term exposure scenarios, including repeated (monthly) and prolonged (3 month) exposures. The PBPK model predictions for Mn in the globus pallidus were compared to background levels and tissue no-effect levels published in earlier studies. Results: The available health-based guidelines for 24- hour acute exposures were highly limited, with only two state regulatory agencies, Texas and Oregon, having developed values. While one was based primarily on respiratory effects (Texas), the other was based on neurological effects associated with longer-term (5.3 year average) exposures among workers (Oregon). From the literature review, two related studies were identified as providing the most relevant point of departure for a 24-hour exposure guideline. These studies both involved inhalation exposure to monkeys and reported respiratory effects (Dorman et al. 2005) and biochemical markers of oxidative stress (Erikson et al. 2008) due to exposures at 1.5 mg Mn/m3 for 5 hours/day, 5 days/week for 3 weeks (90 hours of total exposure). At this exposure, mild and reversible inflammatory airway changes (e.g., mild bronchiolitis, alveolar duct inflammation) and biochemical measures of oxidative stress in the brain were reported. To this LOAEL, we applied a cumulative uncertainty factor of 300 accounting for interspecies, intraspecies, and LOAEL to NOAEL extrapolation, resulting in a 24-hour acute guideline value of 0.005 mg/m3. The PBPK modeling predictions were highest for the 3-month exposure scenario. The highest concentration of Mn in the globus pallidus (0.552 μg/g) from the infant, child, adult model was predicted for male children at 3 years of age. The model predictions are only 3% above background (0.535 μg/g) and returned to baseline less than 6 months following the 3-week exposure scenario. The predictions from the transporter model were similar but slightly higher, and also occurred at 3 years of age. All Mn tissue predictions were below no effect levels for neurological effects reported in the literature from studies of humans and primates, which range from 0.7-0.9 µg/g. Conclusions: Using literature review and PBPK methods, this study supports a 24-hour acute guideline for environmental exposures of 0.005 mg/ m3 Mn for use in air toxics risk assessment. This value is equal to the value set by the Texas Commission on Environmental Quality and 17-times higher than that set by the Oregon Department of Environmental Quality. Because ODEQ is currently re-evaluating its acute Mn guideline, this study provides new information to inform the process and address uncertainties regarding the potential for neurotoxicity from acute exposures.