title: A No Observable Adverse Effects Level (NOAEL) for pigs fed melamine and cyanuric acid.
abstract: Ingesting melamine adulterated milk products led to kidney stones in many infants in 2008. This differs from the renal failure caused by intratubular crystal formation after co-ingestion of melamine (MEL) and cyanuric acid (CYA) in adulterated pet foods in 2007. To better understand the potential risk of developing crystal nephropathy following co-ingestion of MEL and CYA, we fed 16 weanling pigs 0, 1, 3.3, 10, 33, or 100 mg/kg bw/day of each MEL and CYA, or 200 mg/kg bw/day of either compound individually for 7 days. Crystals were found in the renal medulla and cortex and urine sediments of all pigs fed both MEL and CYA each at 10 mg/kg bw/day (or greater). Crystals were also found in one of the two pigs fed 200 mg/kg bw/day MEL-only. In a 28 day study, 36 weanling pigs were fed 0, 1, or 3.3 mg/kg bw/day of MEL and CYA or 200 mg/kg bw/day MEL-only. Only one of the 3.3 mg/kg MEL and CYA pig kidneys contained crystals. The no-observed-adverse-effect level (NOAEL) for pigs fed MEL and CYA for 28 days was concluded to be 1.0 mg/kg bw/day corresponding to 25 mg/kg (ppm) MEL and 25 mg/kg (ppm) CYA in dry feed.
authors.affiliation: Center for Veterinary Medicine, USFDA, Laurel, MD 20708, USA. cynthia.stine@fda.hhs.gov
authors.forename: Cynthia B
authors.initials: CB
authors.lastname: Stine
authors.forename: Renate
authors.initials: R
authors.lastname: Reimschuessel
authors.forename: Charles M
authors.initials: CM
authors.lastname: Gieseker
authors.forename: Eric R
authors.initials: ER
authors.lastname: Evans
authors.forename: Tamara D
authors.initials: TD
authors.lastname: Mayer
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Hasbrouck
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tall
authors.forename: Jamie
authors.initials: J
authors.lastname: Boehmer
authors.forename: Gonçalo
authors.initials: G
authors.lastname: Gamboa da Costa
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Ward
mesh_terms: D000821:Animal Feed / Q000633:toxicity*; D000818:Animals; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007669:Kidney Calculi / Q000139:chemically induced* / Q000473:pathology / Q000652:urine; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D013552:Swine; D014227:Triazines / Q000633:toxicity*
chemical_list: D014227:Triazines; C004632:cyanuric acid; C011907:melamine