Elimination The primary route of Mn elimination is via the fecal hepatobiliary excretion with limited urinary excretion [72]. Some Mn-containing molecules such as Mn-DPDP and Mn nanoparticles show different elimination patterns from the metal Mn [73–75]. Mn is also eliminated in milk as mentioned above. However, this route of elimination does not constitute a major route of Mn excretion. Similarly, very low levels of Mn are excreted in swea In the brain parenchyma, Mn rapidly accumulates in the brain structures such as the superior and inferior colliculi, amygdala, stria terminalis, hippocampus, and globus pallidus. The half-lives of Mn in these tissues are about 5–7 days, with the longest retention in the periaqueductal gray, amygdala, and entorhinal cortex [77]. The elimination rate from brain tissue is expected to be slower than from either liver or kidney. In the rat, the half-lives of 16 brain regions are between 52 and 74 days [6]. In a recent study in rats, we administered Mn by oral gavage at 50 mg/kg for 10 weeks. It was interesting to observe that by the fourth week of dose administration, Mn in blood reached the steady-state concentration, which was maintained for the duration of the study. Mn concentrations in the cerebrospinal fluid, however, continued to increase even at the eight week. It is possible that a slow elimination of Mn from the cerebrospinal fluid may contribute to the high level of Mn in the brain [66••]. It is also possible that a redistribution of Mn from the bone compartment to the central nervous system may account, at least partially, for the high level of Mn in the cerebrospinal fluid. By studying the elimination rate constant and half-lives, our data revealed that the half-lives of Mn in various rat bones were between 77 and 690 days with an average of 143 days for the whole skeleton [66••]. A comparative study between human and rat estimates that every 16.7 days of a rat’s life is equivalent to one human year [78]. By using this figure, the range of Mn half-lives in the rat skeleton is estimated approximately 4.6–41.3 years in humans with an average half-life of 8.6 years for humans