Essentiality, Toxicity, and Uncertainty in the Risk Assessment of Manganese

Risk assessments of manganese by inhalation or oral routes of exposure typically acknowledge the duality of manganese as an essential element at low doses and a toxic metal at high doses. Previously, however, risk assessors were unable to describe manganese pharmacokinetics quantitatively across dose levels and routes of exposure, to account for mass balance, and to incorporate this information into a quantitative risk assessment. In addition, the prior risk assessment of inhaled manganese conducted by the U.S. Environmental Protection Agency (EPA) identified a number of specific factors that contributed to uncertainty in the risk assessment. In response to a petition regarding the use of a fuel additive containing manganese, methylcyclopentadienyl manganese tricarbonyl (MMT), the U.S. EPA developed a test rule under the U.S. Clean Air Act that required, among other things, the generation of pharmacokinetic information. This information was intended not only to aid in the design of health outcome studies,...