1,3,5-triazine-2,4,6(1H,3H,5H)-trione, compound with 1,3,5-triazine-2,4,6-triamine (1:1)

Specific investigations: other studies

Administrative data

Endpoint:

nephrotoxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Limited description of experimental details.

Data source

Reference

Reference Type:

publication

Title:

Determination of Spatial Distribution of Melamine-Cyanuric Acid Crystals in Rat Kidney Tissue by Histology and Imaging Matrix-Assisted Laser Desorption/Ionization Quadrupole Time-of-Flight Mass Spectrometry

Author:

Kim CW, Yun J-W, Bae I-H, Lee J-S, Kang H-J, Joo K-M, Jeong H-J, Chung J-H, Park Y-H,† and Lim K-M

Year:

2010

Bibliographic source:

Chem. Res. Toxicol. 2010, 23, 220–227

Materials and methods

Principles of method if other than guideline:

Spatial distribution of melamine cyanurate crystals in kidney after 3-day feed application

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

repeated dose toxicity: oral

Test material

Test material information

Constituent 1

Details on test material:

obtained from Sigma- Aldrich (St. Louis, MO, USA).

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

age: 5-6 months old
body weight: 250-270 g
Supplier: Orientbio, Seoul, Korea

The animals were housed in polyethylene cages in an environment with a controlled temperature of 24 ( 2 °C, a constant humidity of 50 ( 10%, and a 12 h light-dark cycle. Animals had free access to a standard diet from Purina Korea and tap water ad libitum. The rats were acclimatized for at least 1 week prior to the experiment and were randomly assigned into different groups.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1% in water

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 days

Frequency of treatment:

once daily

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:
25 (12,5 M + 12,5 C), 50 (25 M+25C) and 100 (50 M + 50 C) mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

6

Control animals:

yes, concurrent vehicle

Details on study design:

Thirty minutes before the administration of M+CA, blood samples were collected from the retro-orbital plexus into a vacutainer serum-separating tube (BD Diagnostic, Sparks, MD) for clinical biochemistry using a Selectr E automated analyzer (Vital Scientific, Dieren, Netherlands). For urine collection, rats of the control group and 100 mg/kg/day M+CA-treated group were placed in metabolism cages after the final dose, and urine samples were collected over a 24 h period.
Urine samples were evaluated for creatinine and specific gravity was analyzed with refractometer (ATAGO, Japan). Rats were anesthetized by isoflurane inhalation 24 h after the last dose, and terminal blood samples were obtained from the inferior vena cava for clinical chemistry. Kidneys were removed, weighed, and preserved in 10% neutral-buffered formalin for histopathology.

Examinations

Examinations:

Histopathology of kidneys
Clinical signs
Changes in body weight
Changes in food consumption
BUN
Urea
Creatinine clearance

Positive control:

no

Results and discussion

Details on results:

Visual counting of crystalline deposits shows that rats exposed to a middle dose, 50 mg/kg M+CA, produced renal crystals mainly in the medullar region, while at a high dose, 100 mg/kg M+CA, crystals appeared diffusely throughout the renal cortex and medulla, indicating that M+CA crystals were formed along the osmotic gradient of the kidney. Only the animals with crystals in their kidneys showed increased BUN and creatinine.
Rats given a low dose of 25 mg/kg/day M+CA (12.5 melamine/12.5 cyanuric acid) did not show any evidence of renal impairment or kidney toxicity upon clinical pathologic and histopathologic examination.