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A historical overview of the development of manganese (Mn) pharmacokinetic data under Section 211(b) of the Clean Air Act (CAA)
Citation:
Boyes, W. A historical overview of the development of manganese (Mn) pharmacokinetic data under Section 211(b) of the Clean Air Act (CAA). Manganese2016 Conference, New York, NY, September 25 - 28, 2016.
Impact/Purpose:
describes the data collected under a Clean Air Act test rule and the contribution of that data to the scientific literature regarding susceptibility to manganese exposure. Has implications for Mn risk evaluations under Clean Air Act section 211(b) and residual risk assessments of ferromanganese point source facilities.
Description:
Abstract for Manganese 2016A historical overview of the development of manganese (Mn) pharmacokinetic data under Section 211(b) of the Clean Air Act (CAA)William K BoyesBackground. In the 1990’s, the use of methylcyclopentadienyl manganese tricarbonyl (MMT) as an octane-enhancing gasoline fuel additive led to concerns for potential public health consequences from exposure to Mn combustion products in automotive exhaust. Methods: After a series of regulatory / legal actions and negotiations, the EPA issued under CAA 211(b) an Alternative Tier 2 Test Rule that required development of scientific information intended to help resolve uncertainties in exposure or health risk estimates associated with MMT use. Among the uncertainties identified were: the chemical forms of Mn emitted in automotive exhaust; the relative toxicity of different Mn species; the potential for sensitive subpopulations including females, the young and elderly; differences in sensitivity between test species and humans; differences between inhalation and oral exposures; and the influence of dose rate and exposure duration on tissue accumulation of Mn. It was determined that development of specific sets of pharmacokinetic information and models regarding Mn could help resolve much of the uncertainties identified. Results. The results of the test program included development of several unique Mn PK datasets, and a series of increasingly sophisticated Mn physiologically-based pharmacokinetic (PBPK) models. These data and models have helped address each of the uncertainties originally identified in the test rule. They have also helped evaluate potential risks from other sources of Mn exposure, such as from ferromanganese plants. The results further provide a platform that could expand to cover other potential Mn sources such as drinking water. Conclusion. This influential set of scientific data and models likely would not exist if not for the 211(b) test rule regulatory procedure.