Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs.
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.
Reimschuessel
Renate
R
Center for Veterinary Medicine, US FDA, 8401 Muirkirk Rd, Laurel, MD 20708, USA.
Gieseker
Charles M
CM
Miller
Ron A
RA
Ward
Jeffrey
J
Boehmer
Jamie
J
Rummel
Nathan
N
Heller
David N
DN
Nochetto
Cristina
C
de Alwis
G K Hemakanthi
GK
Bataller
Neal
N
Andersen
Wendy C
WC
Turnipseed
Sherri B
SB
Karbiwnyk
Christine M
CM
Satzger
R Duane
RD
Crowe
John B
JB
Wilber
Nancy R
NR
Reinhard
Mary K
MK
Roberts
John F
JF
Witkowski
Mark R
MR