Pharmacokinetic evaluation of the equivalency of gavage, dietary, and drinking water exposure to manganese in F344 rats.
Concerns exist as to whether individuals may be at greater risk for neurotoxicity following increased manganese (Mn) oral intake. The goals of this study were to determine the equivalence of 3 methods of oral exposure and the rate (mg Mn/kg/day) of exposure. Adult male rats were allocated to control diet (10 ppm), high manganese diet (200 ppm), manganese-supplemented drinking water, and manganese gavage treatment groups. Animals in the drinking water and gavage groups were given the 10 ppm manganese diet and supplemented with manganese chloride (MnCl(2)) in drinking water or once-daily gavage to provide a daily manganese intake equivalent to that seen in the high-manganese diet group. No statistically significant difference in body weight gain or terminal body weights was seen. Rats were anesthetized following 7 and 61 exposure days, and samples of bile and blood were collected. Rats were then euthanized and striatum, olfactory bulb, frontal cortex, cerebellum, liver, spleen, and femur samples were collected for chemical analysis. Hematocrit was unaffected by manganese exposure. Liver and bile manganese concentrations were elevated in all treatment groups on day 61 (relative to controls). Increased cerebellum manganese concentrations were seen in animals from the high-manganese diet group (day 61, relative to controls). Increased (relative to all treatment groups) femur, striatum, cerebellum, frontal cortex, and olfactory bulb manganese concentrations were also seen following gavage suggesting that dose rate is an important factor in the pharmacokinetics of oral manganese. These data will be used to refine physiologically based pharmacokinetic models, extending their utility for manganese risk assessment by including multiple dietary exposures.
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Melanie L
ML
Foster
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Thomas B
TB
Bartnikas
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Laura C
LC
Johnson
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Carolina
C
Herrera
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Michael A
MA
Pettiglio
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Athena M
AM
Keene
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA.
Michael D
MD
Taylor
*North Carolina State University, College of Veterinary Medicine, 1060 William Moore Drive, Raleigh, North Carolina 27607, USA, Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Rm. 522, Providence, Rhode Island 02912, USA, Afton Chemical Corporation, 500 Spring Street, Richmond, Virginia 23219, USA and Nickel Producers Environmental Research Association (NiPERA), 2525 Meridian Parkway, Suite 240 Durham, North Carolina 27713, USA david_dorman@NCSU.edu.
David C
DC
Dorman
D000284:Administration, Oral; D000818:Animals; D001822:Body Burden; D002712:Chlorides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D004032:Diet; D005506:Food Contamination; D008297:Male; D017895:Manganese Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D020149:Manganese Poisoning / Q000209:etiology; D011916:Rats, Inbred F344; D018570:Risk Assessment; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
D002712:Chlorides; D017895:Manganese Compounds; D014874:Water Pollutants, Chemical; C025340:manganese chloride
dose rate; manganese; oral exposure; pharmacokinetics