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Toxicological Sciences 60, 242-251 (2001)
Copyright © 2001 by the Society of Toxicology

BIOTRANSFORMATION AND TOXICOKINETICS

Influence of Dietary Manganese on the Pharmacokinetics of Inhaled Manganese Sulfate in Male CD Rats

David C. Dorman1,, Melanie F. Struve, R. Arden James, Brian E. McManus, Marianne W. Marshall and Brian A. Wong

CIIT Centers for Health Research, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709–2137

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO4). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 ± 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO4/m3. End-of-exposure tissue manganese concentrations and whole-body 54Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO4/m3 had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO4/m3 developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO4 and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO4/m3 also had increased 54Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.

Key Words: manganese; inhalation dietary interactions; biliary elimination; toxicokinetics; rat..


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