title: Old age and gender influence the pharmacokinetics of inhaled manganese sulfate and manganese phosphate in rats.
abstract: In this study, we examined whether gender or age influences the pharmacokinetics of manganese sulfate (MnSO(4)) or manganese phosphate (as the mineral form hureaulite). Young male and female rats and aged male rats (16 months old) were exposed 6 h day(-1) for 5 days week(-1) to air, MnSO(4) (at 0.01, 0.1, or 0.5 mg Mn m(-3)), or hureaulite (0.1 mg Mn m(-3)). Tissue manganese concentrations were determined in all groups at the end of the 90-day exposure and 45 days later. Tissue manganese concentrations were also determined in young male rats following 32 exposure days and 91 days after the 90-day exposure. Intravenous (54)Mn tracer studies were also performed in all groups immediately after the 90-day inhalation to assess whole-body manganese clearance rates. Gender and age did not affect manganese delivery to the striatum, a known target site for neurotoxicity in humans, but did influence manganese concentrations in other tissues. End-of-exposure olfactory bulb, lung, and blood manganese concentrations were higher in young male rats than in female or aged male rats and may reflect a portal-of-entry effect. Old male rats had higher testis but lower pancreas manganese concentrations when compared with young males. Young male and female rats exposed to MnSO(4) at 0.5 mg Mn m(-3) had increased (54)Mn clearance rates when compared with air-exposed controls, while senescent males did not develop higher (54)Mn clearance rates. Data from this study should prove useful in developing dosimetry models for manganese that consider age or gender as potential sensitivity factors.
authors.affiliation: CIIT Centers for Health Research, Research Triangle Park, NC 27709-2137, USA. dorman@ciit.org
authors.forename: David C
authors.initials: DC
authors.lastname: Dorman
authors.forename: Brian E
authors.initials: BE
authors.lastname: McManus
authors.forename: Marianne W
authors.initials: MW
authors.lastname: Marshall
authors.forename: R Arden
authors.initials: RA
authors.lastname: James
authors.forename: Melanie F
authors.initials: MF
authors.lastname: Struve
mesh_terms: D000280:Administration, Inhalation; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D008297:Male; D008345:Manganese / Q000378:metabolism; D017895:Manganese Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D011868:Radioisotopes; D051381:Rats; D012727:Sex Characteristics; D013431:Sulfates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D017895:Manganese Compounds; D009942:Organometallic Compounds; D011868:Radioisotopes; D013431:Sulfates; D008345:Manganese; C406182:manganese phosphate; C039798:manganese sulfate