The intentional adulteration of pet food with melamine and 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 in a range of experimental animals, coexposure can lead to the formation of melamine cyanurate crystals in the nephrons and eventual kidney failure. Given this mode of action, a good understanding of the pharmacokinetic profiles of melamine and cyanuric acid and their combinations is essential to define properly the risk associated with different exposure scenarios. Previous studies have investigated the individual pharmacokinetic profiles of melamine and cyanuric acid. In this work, we report a comparison between the pharmacokinetic profiles of melamine and cyanuric acid administered individually, administered simultaneously as the individual compounds, and administered as a preformed melamine cyanurate complex. Although the oral coadministration of 1 mg/kg body weight of melamine and cyanuric acid did not alter significantly the pharmacokinetic profiles in relation to those determined upon individual oral administration of each compound, the administration of equal amounts of each triazine as the preformed melamine cyanurate complex significantly altered the pharmacokinetics, with reduced bioavailability of both compounds, lower observed maximum serum concentrations, delayed peak concentrations, and prolonged elimination half lives. These results indicate that in order to estimate properly the combined nephrotoxic potential of melamine and cyanuric acid, the experimental design of toxicological experiments and the evaluation of animal or human exposure scenarios should consider the detailed mode of exposure, with particular emphasis on any possible ex vivo formation of melamine cyanurate.
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http://dx.doi.org/10.1093/toxsci/kfr348 | DOI Listing |
Environ Int
December 2024
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, CB#7435, Chapel Hill, NC 27599-7435, United States. Electronic address:
Melamine, its analogues, and aromatic amines (AAs) were commonly detected in a previous study of pregnant women in the Environmental influences on Child Health Outcomes (ECHO) Cohort. While these chemicals have identified toxicities, little is known about their influences on fetal development. We measured these chemicals in gestational urine samples in 3 ECHO cohort sites to assess associations with birth outcomes (n = 1,231).
View Article and Find Full Text PDFChemistry
December 2024
Dipartimento di Scienze Chimiche e Farmaceutiche, Università degli Studi di Trieste, 34127, Trieste, Italy.
In this work, we elucidate the electronic charge redistributions that occur within the cyanuric acid (CA) and melamine (M) molecules upon formation of the triple H-bond between the imide group of CA and the diaminopyridine group of M. To achieve this, we investigated 2D H-bonded assemblies of M, CA and CA*M grown on the Au(111) surface, using X-ray photoemission (XPS) and near edge X-ray absorption fine structure (NEXAFS) spectroscopies. Compared to the homomolecular networks, the spectra of the mixed sample reveal core level shifts in opposite directions for CA and M, indicating a nearly complementary charge accumulation on the CA molecule and a charge depletion on the M molecule.
View Article and Find Full Text PDFEcotoxicol Environ Saf
December 2024
Department of Pediatrics, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China; Department of Chinese Medicine, Jinan Geriatric/Rehabilitation Hospital, Jinan 250013, China; Graduate School of Guangzhou University of Chinese Medicine; Guangzhou 510006, China; Department of Proctology, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China. Electronic address:
Subchronic exposure to cyanuric acid (CA) and its structural analogue melamine induces long-term effects on brain and behavior in male rodents. To examine if this exposure induced negative effects on cognitive function in females, we examined the behavioral performance and further attempted to investigate synaptic and neuronal function. CA was intraperitoneal treated with 20 or 40 mg/kg/day to adolescent female rats for 4 consecutive weeks.
View Article and Find Full Text PDFToxicol Appl Pharmacol
December 2024
Hanford Mission Integration Solutions, Richland, WA, USA. Electronic address:
Int J Biol Macromol
December 2024
School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing 100083, China. Electronic address:
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