Perry C, Proctor D. Short-term environmental inhalation toxicity criteria for airborne manganese protective of neurological and respiratory effects for use in air toxics risk assessment. Presentation 5-15.T-04 to Society of Environmental Toxicology and Chemistry, Pittsburgh PA, November 2022.
Manganese (Mn) is an essential element; the absorption and excretion of which is controlled by homeostasis. As such, derivation of toxicity criteria should consider non-linear toxicokinetics. Mn is also well recognized to cause central nervous system (CNS) effects and respiratory distress in association with high concentration chronic and sub-chronic airborne exposure in some occupations. The need for acute environmental Mn guidelines for regulation of air toxics has recently developed, but only limited data exist to develop a short-term health-based guideline. We reviewed US state, federal, and international health-based environmental inhalation toxicity criteria, as well as occupational exposure limits, and their toxicological bases. Next, a literature search of relevant publications from 2005 though 2022 was performed to capture newly published studies. The study deemed most appropriate to provide the basis for a 24-hour exposure guideline was an inhalation study performed in monkeys exposed 5 hours per day, 5 days/week, for 3 weeks in which a lowest observed adverse effect level (LOAEL) of 1.5 mg/m3 was reported for inflammatory airway changes (e.g., mild bronchiolitis, alveolar duct inflammation). This study was also used by the Texas Commission on Environmental Quality (TCEQ) as a point of departure (POD) for establishing its short-term screening values for Mn. To this POD, we applied a cumulative uncertainty factor of 300 accounting for interspecies, intraspecies, and LOAEL to no observed adverse effect level (NOAEL) extrapolation, resulting in a conservative short-term guideline of 0.005 mg/m3. To assess the potential for CNS effects at this exposure guideline, previously published Mn physiologically based pharmacokinetic (PBPK) models for children and adults were used to predict levels of Mn in the brain (i.e., globus pallidus) for 24-hour exposure at 0.005 mg/m3. The PBPK model predictions for Mn in the globus pallidus were not significantly increased compared to diet alone and background Mn in ambient air, and well below NOAELs of 0.7–0.9 µg/g for neurological effects reported in the literature from human and primate studies. Using refined risk assessment methods, this study supports a short-term guideline for environmental exposures of 0.005 mg/m3 for use in air toxics risk assessment, including welding-fume particulates, which is equal to the TCEQ guideline and 17-times higher than that set by the Oregon Department of Environmental Quality.