ArticleToxicological sciences : an official journal of the Society of Toxicology2011
Dose-response assessment of nephrotoxicity from a 7-day combined exposure to melamine and cyanuric acid in F344 rats.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 58 citations in OpenAlex.
- Depletion of melamine and cyanuric acid in serum from catfish Ictalurus punctatus and rainbow trout Onchorhynchus mykiss.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2012Trial
- Environmental exposure to melamine and its derivatives and kidney outcomes in children.Environmental research · 2024Article
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- Review
- Exposure to melamine and its derivatives and aromatic amines among pregnant women in the United States: The ECHO Program.Chemosphere · 2022Article
- Urinary Excretion of Cyanuric Acid in Association with Urolithiasis: A Matched Case-Control Study in Shanghai Adults.International journal of environmental research and public health · 2022Article
- Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals.EFSA journal. European Food Safety Authority · 2019Article
- Effects of a 28-day dietary co-exposure to melamine and cyanuric acid on the levels of serum microRNAs in male and female Fisher 344 rats.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2016Article
- Ovarian Toxicity in Female Rats after Oral Administration of Melamine or Melamine and Cyanuric Acid.PloS one · 2016Article
- Melamine-cyanurate complexes and oxidative stress markers in trout kidney following melamine and cyanuric acid long-term co-exposure and withdrawal.Fish physiology and biochemistry · 2014Article
- Evaluation of renal toxicity by combination exposure to melamine and cyanuric Acid in male sprague-dawley rats.Toxicological research · 2014Article
- Performance of urinary and gene expression biomarkers in detecting the nephrotoxic effects of melamine and cyanuric acid following diverse scenarios of co-exposure.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2013Article
- Timing and route of exposure affects crystal formation in melamine and cyanuric exposed male and female rats: gavage vs. feeding.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2012Article
- Urinary biomarker detection of melamine- and cyanuric acid-induced kidney injury in rats.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Dose-response assessment of nephrotoxicity from a twenty-eight-day combined-exposure to melamine and cyanuric acid in F344 rats.Toxicology and applied pharmacology · 2012Article
- Pharmacokinetics of melamine and cyanuric acid and their combinations in F344 rats.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- Inhibition of heme peroxidases by melamine.Enzyme research · 2012Article
- Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and cyanuric acid for seven days.Toxicology letters · 2011Article
- A No Observable Adverse Effects Level (NOAEL) for pigs fed melamine and cyanuric acid.Regulatory toxicology and pharmacology : RTP · 2011Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The intentional adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of a large number of cats and dogs in the United States. Although individually these compounds present low toxicity, coexposure can lead to the formation of melamine cyanurate crystals in the nephrons and eventual kidney failure. To determine the dose-response for nephrotoxicity upon coadministration of melamine and cyanuric acid, groups of male and female F344 rats (six animals per sex per group) were fed 0 (control), 7, 23, 69, 229, or 694 ppm of both melamine and cyanuric acid; 1388 ppm melamine; or 1388 ppm cyanuric acid in the diet for 7 days. No toxicity was observed in the rats exposed to the individual compounds, whereas anorexia and a statistically significant increase in blood urea nitrogen and serum creatinine levels was observed in the animals treated with 229 and 694 ppm melamine and cyanuric acid. The kidneys of these animals were grossly enlarged and pale yellow. Large numbers of crystalline structures deposited in the tubules were seen on sections in kidneys from all rats in these treatment groups. No significant changes were detected in the remaining treatment groups exposed to both melamine and cyanuric acid. In the melamine-only treatment group, 5 of 12 rats had scattered crystals present in renal tubules when examined by wet mount. These were not observed by histopathology. The observed adverse effect level (8.6 mg/kg bw [body weight]/day) and benchmark dose modeling data (8.4-10.9 mg/kg bw/day) determined in this study 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.
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