title: Exposure to low-dose barium by drinking water causes hearing loss in mice.
abstract: OBJECTIVE
  We continuously ingest barium as a general element by drinking water and foods in our daily life. Exposure to high-dose barium (>100mg/kg/day) has been shown to cause physiological impairments. Direct administration of barium to inner ears by vascular perfusion has been shown to cause physiological impairments in inner ears. However, the toxic influence of oral exposure to low-dose barium on hearing levels has not been clarified in vivo. We analyzed the toxic influence of oral exposure to low-dose barium on hearing levels and inner ears in mice.
  
  
  METHODS
  We orally administered barium at low doses of 0.14 and 1.4 mg/kg/day to wild-type ICR mice by drinking water. The doses are equivalent to and 10-fold higher than the limit level (0.7 mg/l) of WHO health-based guidelines for drinking water, respectively. After 2-week exposure, hearing levels were measured by auditory brain stem responses and inner ears were morphologically analyzed. After 2-month exposure, tissue distribution of barium was measured by inductively coupled plasma mass spectrometry.
  
  
  RESULTS
  Low-dose barium in drinking water caused severe hearing loss in mice. Inner ears including inner and outer hair cells, stria vascularis and spiral ganglion neurons showed severe degeneration. The Barium-administered group showed significantly higher levels of barium in inner ears than those in the control group, while barium levels in bone did not show a significant difference between the two groups. Barium levels in other tissues including the cerebrum, cerebellum, heart, liver and kidney were undetectably low in both groups.
  
  
  CONCLUSIONS
  Our results demonstrate for the first time that low-dose barium administered by drinking water specifically distributes to inner ears resulting in severe ototoxicity with degeneration of inner ears in mice.
authors.affiliation: Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto, Kasugai, Aichi 487-8501, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.forename: Sohjiro
authors.initials: S
authors.lastname: Hori
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ohgami
authors.forename: Haruka
authors.initials: H
authors.lastname: Tamura
authors.forename: Toyonori
authors.initials: T
authors.lastname: Tsuzuki
authors.forename: Shoko
authors.initials: S
authors.lastname: Ohnuma
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D000161:Acoustic Stimulation; D000162:Acoustics; D000818:Animals; D001464:Barium / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D034381:Hearing Loss / Q000139:chemically induced*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D013054:Spectrophotometry, Atomic / Q000379:methods; D013136:Spiral Ganglion / Q000473:pathology; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D014874:Water Pollutants, Chemical; D001464:Barium