About FDA
Contamination of Human and Animal Food with Melamine and Cyanuric Acid
Description: Conduct a comprehensive toxicokinetic study and assessment of the time-dependency of the no-effect level for a simultaneous exposure to melamine and cyanuric acid (the combination of these two compounds is believed to lead to acute renal failure in dogs and cats and may be responsible for the toxicity observed in infants in China).
For information on the Center for Veterinary Medicine (CVM) study on the 2007 melamine pet food outbreak see The Melamine Story Video.
Definition: Melamine and cyanuric acid are believed to have been the suspected toxicants in the major pet food recall in 2007 that led to acute renal failure in dogs and cats. The development of laboratory techniques to assess melamine and cyanuric acid concentrations in rats (which began in 2009) will help to determine the chemical and biochemical properties of melamine and cyanuric acid that influence their toxicity. This will ultimately provide a better understanding of the toxicity mechanisms of food contaminants and the relationship of toxicity to the amount of the substance ingested.
Public Health Outcome: This study and assessment will help FDA to determine the chemical and biochemical properties of melamine and cyanuric acid that influence their toxicity and determine the appropriate amounts, if any, that should be allowed in human and animal food.
1. 7-day Study
Accomplishment:DBT completed the first of three studies in a comprehensive toxicokinetic study and assessment of the time-dependency of the no-effect level for a simultaneous exposure to melamine and cyanuric acid. The first study was over the course of 7 days and resulted in a manuscript accepted for publication in Toxicological Sciences. The results suggest that the tolerable daily intake values derived from studies conducted with melamine alone may underestimate the risk from coexposures to melamine and cyanuric acid. Researchers hope that this study will help FDA to determine the chemical and biochemical properties of melamine and cyanuric acid that influence their toxicity and determine the appropriate amounts, if any, that should be allowed in human and animal food.
| Milestone Description | Milestone Date | Milestone Status | Milestone Completion Date |
|---|---|---|---|
|
a. Prepare and submit manuscript on the outcome of the 7-day combined melamine and cyanuric rodent study |
8/15/2010 |
Completed | 8/6/2010 |
|
b. Publish manuscript in scientific journal |
10/30/2010 |
Completed | 10/24/2010 |
2. 28-day Study
Accomplishment:The aim of this study was to determine if urinary biomarkers of acute kidney injury can be used tononinvasively detect renal damage associated with crystal formation in the kidneys ofmelamine and cyanuric acid-exposed rats. The data from this study indicate certain urinary protein biomarkers may serveas a noninvasive biomarker for the detection and monitoring of obstructive nephropathy associated with melamine-cyanuric acid exposure. Early and sensitive biomarkers. of nephrotoxicity are valuable in drug discovery, preclinical safety evaluation of drugsand medical device materials, clinical trials, and evaluation of toxic responses followingexposure to environmental toxicants. Please find the full text, including the abstract, in: http://toxsci.oxfordjournals.org/content/early/2012/05/19/toxsci.kfs182.full.pdf+html
Briefing Status: COMPLETED
Prior Briefing Status: ON TRACK
| Milestone Description | Milestone Date | Milestone Status | Milestone Completion Date |
|---|---|---|---|
|
a. Compile and analyze main outcomes of the 28-day combined melamine and cyanuric acid study |
4/30/2010 |
Completed | 4/30/2010 |
|
b. Present the main outcomes of the 28-day combined melamine and cyanuric acid study to the TSSRC meeting |
5/31/2010 |
Completed | 5/18/2010 |
|
c. Develop draft manuscript on the outcome of the 28-day combined melamine and cyanuric acid study |
1/30/2011 (9/30/2011) (TBD) |
Completed | 2/10/2012 |
|
d. Complete the peer review (NCTR and other researchers) of manuscript |
TBD |
Completed | 2/20/2012 |
|
e. Obtain NCTR Center Director approval on the draft manuscript via the document tracking system |
TBD |
Completed | 3/8/2012 |
|
f. Submit final manuscript on the outcome of the 28-day combined melamine and cyanuric acid study to a scientific journal |
TBD |
Completed | 3/10/2012 |
3. 90-day Study
Briefing Status: ON TRACK
Prior Briefing Status: ON TRACK
| Milestone Description | Milestone Date | Milestone Status | Milestone Completion Date |
|---|---|---|---|
|
a. Decide upon design of 90-day study |
5/31/2010 |
Completed | 5/18/2010 |
|
b. Finalize and submit the 90-day combined melamine and cyanuric acid rat study protocol |
10/31/2010 (12/30/2010) |
Completed | 12/18/2010 |
|
c. Complete 90-day combined melamine and cyanuric acid exposure study |
6/30/2011 (12/1/2011) |
Completed | 11/9/2011 |
|
d. Develop draft report on the outcome of the 90-day combined melamine and cyanuric acid exposure study |
TBD |
Not Yet Started | |
|
e. Complete the peer review (NCTR and other researchers) of report |
TBD |
Not Yet Started | |
|
f. Obtain NCTR Center Director approval on the draft report via the document tracking system |
TBD |
Not Yet Started | |
|
g. Submit NCTR final report on 90-day combined melamine and cyanuric acid exposure study |
TBD |
Not Yet Started |
4. Neonate (Newborn) Study
Briefing Status: ON TRACK
Prior Briefing Status: ON TRACK
| Milestone Description | Milestone Date | Milestone Status | Milestone Completion Date |
|---|---|---|---|
|
a. Prepare and submit the neonate combined melamine and cyanuric acid study protocol |
1/30/2011 (9/30/2011) |
Completed | 3/8/2012 |
|
b. Complete neonate combined melamine and cyanuric acid exposure study |
TBD |
Not Yet Started | |
|
c. Develop draft report on the outcome of the neonate combined melamine and cyanuric acid exposure study |
TBD |
Not Yet Started | |
|
d. Complete the peer review (NCTR and other researchers) of report |
TBD |
Not Yet Started | |
|
e. Obtain NCTR Center Director approval on the draft report via the document tracking system |
TBD |
Not Yet Started | |
|
f. Submit NCTR final report on the neonate combined melamine and cyanuric acid exposure study |
TBD |
Not Yet Started |
Key Projects Legend
| Milestone Status | Definition |
|---|---|
| Not Yet Started | Work for specific milestone has not yet been started. |
| Completed | Milestone and/or overall project is completed. |
| On Track | Milestone - On track for completion by milestone deadline. Quarter status - Project is on track for completion based on overall milestone status. |
| On Hold | Milestone - On hold, but deadline for completion has not passed. Quarter status - Project is on hold, based on overall milestone status. |
| Delayed | Milestone - Delayed as it has not been completed and deadline has passed. Quarter status - Project is delayed based on overall milestone status. |
Glossary
TSSRC
Toxicology Study Selection and Review Committee
Note: The data provided on this website is produced on an ongoing basis for performance management purposes and is subject to change due to updates of preliminary estimates, corrections, or other reasons. In addition, FDA may change the type or amount of data provided on this website at any time. Information marked as "Completed" may include measures and/or key projects for which activities are ongoing but no longer tracked as part of FDA-TRACK.
