title: Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs.
abstract: OBJECTIVE
  To determine whether renal crystals can be experimentally induced in animals fed melamine or the related triazine compound cyanuric acid, separately or in combination, and to compare experimentally induced crystals with those from a cat with triazine-related renal failure.
  
  
  METHODS
  75 fish (21 tilapia, 24 rainbow trout, 15 channel catfish, and 15 Atlantic salmon), 4 pigs, and 1 cat that was euthanatized because of renal failure.
  
  
  METHODS
  Fish and pigs were fed a target dosage of melamine (400 mg/kg), cyanuric acid (400 mg/kg), or melamine and cyanuric acid (400 mg of each compound/kg) daily for 3 days and were euthanatized 1, 3, 6, 10, or 14 days after administration ceased. Fresh, frozen, and formalin-fixed kidneys were examined for crystals. Edible tissues were collected for residue analysis. Crystals were examined for composition via Raman spectroscopy and hydrophilic-interaction liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  All animals fed the combination of melamine and cyanuric acid developed goldbrown renal crystals arranged in radial spheres (spherulites), similar to those detected in the cat. Spectral analyses of crystals from the cat, pigs, and fish were consistent with melamine-cyanurate complex crystals. Melamine and cyanuric acid residues were identified in edible tissues of fish.
  
  
  CONCLUSIONS
  Although melamine and cyanuric acid appeared to have low toxicity when administered separately, they induced extensive renal crystal formation when administered together. The subsequent renal failure may be similar to acute uric acid nephropathy in humans, in which crystal spherulites obstruct renal tubules.
authors.affiliation: Center for Veterinary Medicine, US FDA, 8401 Muirkirk Rd, Laurel, MD 20708, USA.
authors.forename: Renate
authors.initials: R
authors.lastname: Reimschuessel
authors.forename: Charles M
authors.initials: CM
authors.lastname: Gieseker
authors.forename: Ron A
authors.initials: RA
authors.lastname: Miller
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ward
authors.forename: Jamie
authors.initials: J
authors.lastname: Boehmer
authors.forename: Nathan
authors.initials: N
authors.lastname: Rummel
authors.forename: David N
authors.initials: DN
authors.lastname: Heller
authors.forename: Cristina
authors.initials: C
authors.lastname: Nochetto
authors.forename: G K Hemakanthi
authors.initials: GK
authors.lastname: de Alwis
authors.forename: Neal
authors.initials: N
authors.lastname: Bataller
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Andersen
authors.forename: Sherri B
authors.initials: SB
authors.lastname: Turnipseed
authors.forename: Christine M
authors.initials: CM
authors.lastname: Karbiwnyk
authors.forename: R Duane
authors.initials: RD
authors.lastname: Satzger
authors.forename: John B
authors.initials: JB
authors.lastname: Crowe
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Wilber
authors.forename: Mary K
authors.initials: MK
authors.lastname: Reinhard
authors.forename: John F
authors.initials: JF
authors.lastname: Roberts
authors.forename: Mark R
authors.initials: MR
authors.lastname: Witkowski