A fundamental question to be addressed in this study is whether exposure to inhaled manganese (Mn) is likely to be safe or neurotoxic at realistic environmental exposure levels. Mn is an essential trace metal that is also a component of methylcyclopentadienyl, manganese tricarbonyl (MMT), an octane enhancer for use in unleaded automotive gasoline. Following MMT combustion, a variety of Mn-containing compounds are produced, with the phosphate being the most significant species emitted from the automobile's tail pipe. The proposed use of MMT-containing automotive fuels may result in increased inhalation exposure of the public to Mn. Although Mn is known to be neurotoxic in humans following prolonged exposure to high concentrations (greater than 10 mg/m3), there is very little data on the risks associated with low dose inhalation exposure. The ultimate goal of this study is to improve human risk assessment for Mn released from MMT-containing gasoline by providing critical data regarding the exposure-response relationship to Mn phosphate. Adult rodents and non-human primates will be exposed to low-exposure concentrations of Mn phosphate, and data concerning Mn accumulation in the nervous system and its resulting effects on neurochemistry will be collected. Additionally, the possibility that developing humans may be at increased risk for Mn toxicity will be investigated by conducting developmental neurotoxicology studies in rats.
| Kocarek, Thomas A; Duanmu, Zhengbo; Fang, Hai-Lin et al. (2008) Age- and sex-dependent expression of multiple murine hepatic hydroxysteroid sulfotransferase (SULT2A) genes. Biochem Pharmacol 76:1036-46 |
