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Lawrence P Wackett - One of the best experts on this subject based on the ideXlab platform.
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Cyanuric Acid biodegradation via biuret physiology taxonomy and geospatial distribution
Applied and Environmental Microbiology, 2019Co-Authors: Kelly G. Aukema, Lambros J Tassoulas, Serina L Robinson, Jessica F Konopatski, Madison D Bygd, Lawrence P WackettAbstract:ABSTRACT Cyanuric Acid is an industrial chemical produced during the biodegradation of s-triazine pesticides. The biodegradation of Cyanuric Acid has been elucidated using a single model system, Pseudomonas sp. strain ADP, in which Cyanuric Acid hydrolase (AtzD) opens the s-triazine ring and AtzEG deaminates the ring-opened product. A significant question remains as to whether the metabolic pathway found in Pseudomonas sp. ADP is the exception or the rule in bacterial genomes globally. Here, we show that most bacteria utilize a different pathway, metabolizing Cyanuric Acid via biuret. The new pathway was determined by reconstituting the pathway in vitro with purified enzymes and by mining more than 250,000 genomes and metagenomes. We isolated soil bacteria that grow on Cyanuric Acid as a sole nitrogen source and showed that the genome from a Herbaspirillum strain had a canonical Cyanuric Acid hydrolase gene but different flanking genes. The flanking gene trtB encoded an enzyme that we show catalyzed the decarboxylation of the Cyanuric Acid hydrolase product, carboxybiuret. The reaction generated biuret, a pathway intermediate further transformed by biuret hydrolase (BiuH). The prevalence of the newly defined pathway was determined by cooccurrence analysis of Cyanuric Acid hydrolase genes and flanking genes. Here, we show the biuret pathway was more than 1 order of magnitude more prevalent than the original Pseudomonas sp. ADP pathway. Mining a database of over 40,000 bacterial isolates with precise geospatial metadata showed that bacteria with concurrent Cyanuric Acid and biuret hydrolase genes were distributed throughout the United States. IMPORTANCE Cyanuric Acid is produced naturally as a contaminant in urea fertilizer, and it is used as a chlorine stabilizer in swimming pools. Cyanuric Acid-degrading bacteria are used commercially in removing Cyanuric Acid from pool water when it exceeds desired levels. The total volume of Cyanuric Acid produced annually exceeds 200 million kilograms, most of which enters the natural environment. In this context, it is important to have a global understanding of Cyanuric Acid biodegradation by microbial communities in natural and engineered systems. Current knowledge of Cyanuric Acid metabolism largely derives from studies on the enzymes from a single model organism, Pseudomonas sp. ADP. In this study, we obtained and studied new microbes and discovered a previously unknown Cyanuric Acid degradation pathway. The new pathway identified here was found to be much more prevalent than the pathway previously established for Pseudomonas sp. ADP. In addition, the types of environment, taxonomic prevalences, and geospatial distributions of the different Cyanuric Acid degradation pathways are described here.
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crystal structures of moorella thermoacetica Cyanuric Acid hydrolase reveal conformational flexibility and asymmetry important for catalysis
PLOS ONE, 2019Co-Authors: Ke Shi, Kelly G. Aukema, Asim K. Bera, Lawrence P Wackett, Jennifer L Seffernick, Seunghee Cho, Thomas Lee, Hideki AiharaAbstract:An ancient enzyme family responsible for the catabolism of the prebiotic chemical Cyanuric Acid (1,3,5-triazine-2,4,6-triol) was recently discovered and is undergoing proliferation in the modern world due to industrial synthesis and dissemination of 1,3,5-triazine compounds. Cyanuric Acid has a highly stabilized ring system such that bacteria require a unique enzyme with a novel fold and subtle active site construction to open the ring. Each Cyanuric Acid hydrolase monomer consists of three isostructural domains that coordinate and activate the three-fold symmetric substrate Cyanuric Acid for ring opening. We have now solved a series of X-ray structures of an engineered, thermostable Cyanuric Acid ring-opening enzyme at 1.51 ~ 2.25 A resolution, including various complexes with the substrate, a tight-binding inhibitor, or an analog of the reaction intermediate. These structures reveal asymmetric interactions between the enzyme and bound ligands, a metal ion binding coupled to conformational changes and substrate binding important for enzyme stability, and distinct roles of the isostructural domains of the enzyme. The multiple conformations of the enzyme observed across a series of structures and corroborating biochemical data suggest importance of the structural dynamics in facilitating the substrate entry and the ring-opening reaction, catalyzed by a conserved Ser-Lys dyad.
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Structure of the Cyanuric Acid Hydrolase TrzD Reveals Product Exit Channel
Scientific Reports, 2017Co-Authors: Asim K. Bera, Kelly G. Aukema, Mikael Elias, Lawrence P WackettAbstract:Cyanuric Acid hydrolases are of industrial importance because of their use in aquatic recreational facilities to remove Cyanuric Acid, a stabilizer for the chlorine. Degradation of excess Cyanuric Acid is necessary to maintain chlorine disinfection in the waters. Cyanuric Acid hydrolase opens the Cyanuric Acid ring hydrolytically and subsequent decarboxylation produces carbon dioxide and biuret. In the present study, we report the X-ray structure of TrzD, a Cyanuric Acid hydrolase from Acidovorax citrulli. The crystal structure at 2.19 A resolution shows a large displacement of the catalytic lysine (Lys163) in domain 2 away from the active site core, whereas the two other active site lysines from the two other domains are not able to move. The lysine displacement is proposed here to open up a channel for product release. Consistent with that, the structure also showed two molecules of the co-product, carbon dioxide, one in the active site and another trapped in the proposed exit channel. Previous data indicated that the domain 2 lysine residue plays a role in activating an adjacent serine residue carrying out nucleophilic attack, opening the Cyanuric Acid ring, and the mobile lysine guides products through the exit channel.
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Ancient Evolution and Recent Evolution Converge for the Biodegradation of Cyanuric Acid and Related Triazines.
Applied and environmental microbiology, 2016Co-Authors: Jennifer L Seffernick, Lawrence P WackettAbstract:Cyanuric Acid was likely present on prebiotic Earth, may have been a component of early genetic materials, and is synthesized industrially today on a scale of more than one hundred million pounds per year in the United States. In light of this, it is not surprising that some bacteria and fungi have a metabolic pathway that sequentially hydrolyzes Cyanuric Acid and its metabolites to release the nitrogen atoms as ammonia to support growth. The initial reaction that opens the s-triazine ring is catalyzed by the unusual enzyme Cyanuric Acid hydrolase. This enzyme is in a rare protein family that consists of only Cyanuric Acid hydrolase (CAH) and barbiturase, with barbiturase participating in pyrimidine catabolism by some actinobacterial species. The X-ray structures of two Cyanuric Acid hydrolase proteins show that this family has a unique protein fold. Phylogenetic, bioinformatic, enzymological, and genetic studies are consistent with the idea that CAH has an ancient protein fold that was rare in microbial populations but is currently becoming more widespread in microbial populations in the wake of anthropogenic synthesis of Cyanuric Acid and other s-triazine compounds that are metabolized via a Cyanuric Acid intermediate. The need for the removal of Cyanuric Acid from swimming pools and spas, where it is used as a disinfectant stabilizer, can potentially be met using an enzyme filtration system. A stable thermophilic Cyanuric Acid hydrolase from Moorella thermoacetica is being tested for this purpose.
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Silica Gel for Enhanced Activity and Hypochlorite Protection of Cyanuric Acid Hydrolase in Recombinant Escherichia coli
mBio, 2015Co-Authors: Adi Radian, Kelly G. Aukema, Alptekin Aksan, Lawrence P WackettAbstract:ABSTRACT Chlorinated isoCyanuric Acids are widely used water disinfectants that generate hypochlorite, but with repeated application, they build up Cyanuric Acid (CYA) that must be removed to maintain disinfection. 3-Aminopropyltriethoxysilane (APTES)-treated Escherichia coli cells expressing Cyanuric Acid hydrolase (CAH) from Moorella thermoacetica exhibited significantly high CYA degradation rates and provided protection against enzyme inactivation by hypochlorite (chlorine). APTES coating or encapsulation of cells had two benefits: (i) overcoming diffusion limitations imposed by the cell wall and (ii) protecting against hypochlorite inactivation of CAH activity. Cells encapsulated in APTES gels degraded CYA three times faster than nonfunctionalized tetraethoxysilane (TEOS) gels, and cells coated with APTES degraded CYA at a rate of 29 µmol/min per mg of CAH protein, similar to the rate with purified enzyme. UV spectroscopy, fluorescence spectroscopy, and scanning electron microscopy showed that the higher rates were due to APTES increasing membrane permeability and enhancing Cyanuric Acid diffusion into the cytoplasm to reach the CAH enzyme. Purified CAH enzyme was shown to be rapidly inactivated by hypochlorite. APTES aggregates surrounding cells protected via the amine groups reacting with hypochlorite as shown by pH changes, zeta potential measurements, and infrared spectroscopy. APTES-encapsulated E. coli cells expressing CAH degraded Cyanuric Acid at high rates in the presence of 1 to 10 ppm hypochlorite, showing effectiveness under swimming pool conditions. In contrast, CAH activity in TEOS gels or free cells was completely inactivated by hypochlorite. These studies show that commercially available silica materials can selectively enhance, protect, and immobilize whole-cell biocatalysts for specialized applications. IMPORTANCE Hypochlorite is used in vast quantities for water disinfection, killing bacteria on surfaces, and washing and whitening. In pools, spas, and other waters, hypochlorite is frequently delivered as chlorinated isoCyanuric Acids that release hypochlorite and Cyanuric Acid. Over time, Cyanuric Acid accumulates and impairs disinfection and must be removed. The microbial enzyme Cyanuric Acid hydrolase can potentially remove Cyanuric Acid to restore disinfection and protect swimmers. Whole bacterial cells expressing Cyanuric Acid hydrolase were encapsulated in an inert silica matrix containing an amine group. The amine group serves to permeabilize the cell membrane and accelerate Cyanuric Acid degradation, and it also reacts with hypochlorite to protect against inactivation of Cyanuric Acid hydrolase. Methods for promoting whole-cell biocatalysis are important in biotechnology, and the present work illustrates approaches to enhance rates and protect against an inhibitory substance.
Bao S. Liu - One of the best experts on this subject based on the ideXlab platform.
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The effects of melamine on humoral immunity with or without Cyanuric Acid in mice.
Research in veterinary science, 2016Co-Authors: Rong H. Yin, Xin Wang, Rong L. Yin, Jiao Liu, Qiao Dong, Wen C. Wang, Jing Yuan, Bao S. LiuAbstract:Melamine is an industrial chemical with high nitrogen content. When added to the pet food and milk it can falsely elevate the apparent protein concentration readings. Cyanuric Acid related structurally to melamine has a strong mutual affinity with melamine. The combined ingestion of melamine and Cyanuric Acid was considered to be responsible for the crystalluria, kidney stones and subsequent renal failure in animals. In our previous investigation, we demonstrated that melamine alone or its combination with Cyanuric Acid appears to be toxic to the immune system in mice. The objective of this study was to investigate the potential effects of melamine on humoral immunity with or without Cyanuric Acid in mice. In comparison to control group, a significantly lower content of plasma cells expressing CD138 were observed in mixture groups of melamine and Cyanuric Acid with both middle and high doses. The co-administration of melamine and Cyanuric Acid resulted in a significant decreasing in blimp-1 protein expression and the contents of sIgA, C3, IL-21 and IL-4 compared with the control group. Moreover, our data clearly showed that melamine-related toxicity suppressed the production of IL-6 and IL-10 in a dose-dependent manner. Also, the animals from mixture of melamine and Cyanuric Acid with high dose group exhibited a significantly lower expression of gata-3 protein, The results from the present study suggested that the exposure to melamine alone or combination with Cyanuric Acid had certain humoral immunotoxicity in mice, especially when ingested in high dosage.
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the reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice
Research in Veterinary Science, 2013Co-Authors: Rong H. Yin, Rong L. Yin, Jiao Liu, Xin Z Wang, Wen L Bai, Bao S. LiuAbstract:Melamine, a chemical compound, was used widely in the manufacture of amino resins and plastics. Cyanuric Acid related structurally to melamine was used as a water stabilizer in swimming pools. The combination of melamine and Cyanuric Acid was thought to be responsible for renal impairment in mammals. In the present work, we investigated the reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice. Pathological damages in different degrees were observed in the testis of male mice treated with different doses of both melamine alone and combination of melamine and Cyanuric Acid in a dose-dependent manner. Based on the TUNEL assay, the mice treated with high dose of melamine (50 mg/kg/day) had a significant increase in apoptotic index of spermatogenic cells (p<0.05) compared with the control group. Sperm abnormality test indicated that melamine alone resulted in abnormal sperm morphology. The mice from co-administration groups of melamine and Cyanuric Acid were not eating, and were most likely in renal failure. The combined exposure to melamine and Cyanuric Acid was revealed to have certain toxic effects on testis of male mice at a relative low dose (each at 1 mg/kg/day). Also, in comparison to melamine treated groups, more severe apoptosis was observed in co-administration groups of melamine and Cyanuric Acid with both middle (each at 5 mg/kg/day) and high doses (each at 25 mg/kg/day). However, all mice administrated with combination of melamine and Cyanuric Acid (each at 206, 412, or 824 mg/kg/day) died before day 6 from which no data were obtained on sperm abnormality. These results from this study demonstrated that melamine had certain toxic effects on testes of male mice, especially when ingested in high concentration. These results might be useful in evaluating the toxicity of melamine on reproductive system of male animal, and they also would be a supplement to the existing toxic profile of melamine.
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The reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice.
Research in veterinary science, 2012Co-Authors: Rong H. Yin, Rong L. Yin, Jiao Liu, Xin Z Wang, Wen L Bai, Bao S. LiuAbstract:Melamine, a chemical compound, was used widely in the manufacture of amino resins and plastics. Cyanuric Acid related structurally to melamine was used as a water stabilizer in swimming pools. The combination of melamine and Cyanuric Acid was thought to be responsible for renal impairment in mammals. In the present work, we investigated the reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice. Pathological damages in different degrees were observed in the testis of male mice treated with different doses of both melamine alone and combination of melamine and Cyanuric Acid in a dose-dependent manner. Based on the TUNEL assay, the mice treated with high dose of melamine (50 mg/kg/day) had a significant increase in apoptotic index of spermatogenic cells (p
Rong H. Yin - One of the best experts on this subject based on the ideXlab platform.
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The effects of melamine on humoral immunity with or without Cyanuric Acid in mice.
Research in veterinary science, 2016Co-Authors: Rong H. Yin, Xin Wang, Rong L. Yin, Jiao Liu, Qiao Dong, Wen C. Wang, Jing Yuan, Bao S. LiuAbstract:Melamine is an industrial chemical with high nitrogen content. When added to the pet food and milk it can falsely elevate the apparent protein concentration readings. Cyanuric Acid related structurally to melamine has a strong mutual affinity with melamine. The combined ingestion of melamine and Cyanuric Acid was considered to be responsible for the crystalluria, kidney stones and subsequent renal failure in animals. In our previous investigation, we demonstrated that melamine alone or its combination with Cyanuric Acid appears to be toxic to the immune system in mice. The objective of this study was to investigate the potential effects of melamine on humoral immunity with or without Cyanuric Acid in mice. In comparison to control group, a significantly lower content of plasma cells expressing CD138 were observed in mixture groups of melamine and Cyanuric Acid with both middle and high doses. The co-administration of melamine and Cyanuric Acid resulted in a significant decreasing in blimp-1 protein expression and the contents of sIgA, C3, IL-21 and IL-4 compared with the control group. Moreover, our data clearly showed that melamine-related toxicity suppressed the production of IL-6 and IL-10 in a dose-dependent manner. Also, the animals from mixture of melamine and Cyanuric Acid with high dose group exhibited a significantly lower expression of gata-3 protein, The results from the present study suggested that the exposure to melamine alone or combination with Cyanuric Acid had certain humoral immunotoxicity in mice, especially when ingested in high dosage.
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the reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice
Research in Veterinary Science, 2013Co-Authors: Rong H. Yin, Rong L. Yin, Jiao Liu, Xin Z Wang, Wen L Bai, Bao S. LiuAbstract:Melamine, a chemical compound, was used widely in the manufacture of amino resins and plastics. Cyanuric Acid related structurally to melamine was used as a water stabilizer in swimming pools. The combination of melamine and Cyanuric Acid was thought to be responsible for renal impairment in mammals. In the present work, we investigated the reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice. Pathological damages in different degrees were observed in the testis of male mice treated with different doses of both melamine alone and combination of melamine and Cyanuric Acid in a dose-dependent manner. Based on the TUNEL assay, the mice treated with high dose of melamine (50 mg/kg/day) had a significant increase in apoptotic index of spermatogenic cells (p<0.05) compared with the control group. Sperm abnormality test indicated that melamine alone resulted in abnormal sperm morphology. The mice from co-administration groups of melamine and Cyanuric Acid were not eating, and were most likely in renal failure. The combined exposure to melamine and Cyanuric Acid was revealed to have certain toxic effects on testis of male mice at a relative low dose (each at 1 mg/kg/day). Also, in comparison to melamine treated groups, more severe apoptosis was observed in co-administration groups of melamine and Cyanuric Acid with both middle (each at 5 mg/kg/day) and high doses (each at 25 mg/kg/day). However, all mice administrated with combination of melamine and Cyanuric Acid (each at 206, 412, or 824 mg/kg/day) died before day 6 from which no data were obtained on sperm abnormality. These results from this study demonstrated that melamine had certain toxic effects on testes of male mice, especially when ingested in high concentration. These results might be useful in evaluating the toxicity of melamine on reproductive system of male animal, and they also would be a supplement to the existing toxic profile of melamine.
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The reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice.
Research in veterinary science, 2012Co-Authors: Rong H. Yin, Rong L. Yin, Jiao Liu, Xin Z Wang, Wen L Bai, Bao S. LiuAbstract:Melamine, a chemical compound, was used widely in the manufacture of amino resins and plastics. Cyanuric Acid related structurally to melamine was used as a water stabilizer in swimming pools. The combination of melamine and Cyanuric Acid was thought to be responsible for renal impairment in mammals. In the present work, we investigated the reproductive toxicity of melamine in the absence and presence of Cyanuric Acid in male mice. Pathological damages in different degrees were observed in the testis of male mice treated with different doses of both melamine alone and combination of melamine and Cyanuric Acid in a dose-dependent manner. Based on the TUNEL assay, the mice treated with high dose of melamine (50 mg/kg/day) had a significant increase in apoptotic index of spermatogenic cells (p
Eduardo Santero - One of the best experts on this subject based on the ideXlab platform.
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Genetic evidence of a high-affinity Cyanuric Acid transport system in Pseudomonas sp. ADP
FEMS microbiology letters, 2014Co-Authors: Ana Isabel Platero, Eduardo Santero, Fernando GovantesAbstract:The Pseudomonas sp. ADP plasmid pADP-1 encodes the activities involved in the hydrolytic degradation of the s -triazine herbicide atrazine. Here, we explore the presence of a specific transport system for the central intermediate of the atrazine utilization pathway, Cyanuric Acid, in Pseudomonas sp. ADP. Growth in fed-batch cultures containing limiting Cyanuric Acid concentrations is consistent with high-affinity transport of this substrate. Acquisition of the ability to grow at low Cyanuric Acid concentrations upon conjugal transfer of pADP1 to the nondegrading host Pseudomonas putida KT2442 suggests that all activities required for this phenotype are encoded in this plasmid. Co-expression of the pADP1-borne atzDEF and atzTUVW genes, encoding the Cyanuric Acid utilization pathway and the subunits of an ABC-type solute transport system, in P. putida KT2442 was sufficient to promote growth at Cyanuric Acid concentrations as low as 50 μM in batch culture. Taken together, our results strongly suggest that the atzTUVW gene products are involved in high-affinity transport of Cyanuric Acid.
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Regulation of the Pseudomonas sp. Strain ADP Cyanuric Acid Degradation Operon
Journal of bacteriology, 2005Co-Authors: Vicente García-gonzález, Fernando Govantes, Odil Porrúa, Eduardo SanteroAbstract:Pseudomonas sp. strain ADP is the model strain for studying bacterial degradation of the s- triazine herbicide atrazine. In this work, we focused on the expression of the atzDEF operon, involved in mineralization of the central intermediate of the pathway, Cyanuric Acid. Expression analysis of atzD-lacZ fusions in Pseudomonas sp. strain ADP and Pseudomonas putida showed that atzDEF is subjected to dual regulation in response to nitrogen limitation and Cyanuric Acid. The gene adjacent to atzD , orf99 (renamed here atzR ), encoding a LysR-like regulator, was found to be required for both responses. Expression of atzR-lacZ was induced by nitrogen limitation and repressed by AtzR. Nitrogen regulation of atzD-lacZ and atzR-lacZ expression was dependent on the alternative σ factor σ N and NtrC, suggesting that the Cyanuric Acid degradation operon may be subject to general nitrogen control. However, while atzR is transcribed from a σ N -dependent promoter, atzDEF transcription appears to be driven from a σ 70 -type promoter. Expression of atzR from a heterologous promoter revealed that although NtrC regulation of atzD-lacZ requires the AtzR protein, it is not the indirect result of NtrC-activated AtzR synthesis. We propose that expression of the Cyanuric Acid degradation operon atzDEF is controlled by means of a complex regulatory circuit in which AtzR is the main activator. AtzR activity is in turn modulated by the presence of Cyanuric Acid and by a nitrogen limitation signal transduced by the Ntr system.
Kurunthachalam Kannan - One of the best experts on this subject based on the ideXlab platform.
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Occurrence and Profiles of Melamine and Cyanuric Acid in Bovine Feed and Urine from China, India, and the United States
2019Co-Authors: Hongkai Zhu, Bommanna G. Loganathan, Kurunthachalam KannanAbstract:Melamine and Cyanuric Acid have been reported to occur in animal products. Nevertheless, information that pertains to the occurrence of melamine and Cyanuric Acid in cattle feed and urine is lacking. In this study, the occurrence of melamine and its three derivatives (i.e., Cyanuric Acid, ammeline, and ammelide) was determined in 183 bovine urine and 29 matched feed samples collected from China, India, and the United States. ∑Melamine (sum of four target compounds) was found in all urine samples at concentrations that ranged from 4.2 to 5280 ng/mL (median: 370 ng/mL); Cyanuric Acid was the major derivative, accounting for 97% of the total concentrations, followed by melamine (2.2%). The ubiquitous occurrence of ∑Melamine in feed (21–6230 ng/g) suggests that it is the major source of melamine and its derivatives in bovines. Urinary concentrations of melamine and Cyanuric Acid varied significantly among the three countries, with samples from China as having the highest concentrations, followed by the United States and India. The calculated cumulative daily intakes of melamine and Cyanuric Acid were at least 10-fold below the current tolerable daily intake recommended for humans. Our study provides evidence-based data on exposure patterns and sources of melamine and Cyanuric Acid in cattle
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Fertilizers as a Source of Melamine and Cyanuric Acid in Soils: A Nationwide Survey in China
2019Co-Authors: Hongkai Zhu, Yu Wang, Hongwen Sun, Kurunthachalam KannanAbstract:The use of melamine and Cyanuric Acid in agriculture, industry, and consumer products has led to their ubiquitous environmental distribution. Nevertheless, little is known about the contamination of soils by melamine and Cyanuric Acid. Contamination of soils with melamine can lead to plant uptake and food chain transfer of these chemicals. In this study, concentrations of melamine and its three derivatives (Cyanuric Acid, ammeline, and ammelide) were determined in 98 surface soils and 16 fertilizers collected across China in 2017. Elevated concentrations of ∑melamine (sum of melamine and its three derivatives) were found in soils at concentrations that ranged from 8.67 to 2020 ng/g dry weight (dw), with an average value of 213 ng/g dw. Melamine accounted for 63% of the total concentrations in soils, which was followed by Cyanuric Acid (28%). Elevated concentrations of melamine and Cyanuric Acid were found in nitrogenous fertilizers such as nitrolime (n = 3; mean: 284 μg/g) and urea (n = 4; mean: 3160 μg/g), respectively. The measured concentrations in fertilizers were 3 to 4 orders of magnitude higher than those found in soils. Farmland soils (mean: 545 ng/g dw) contained significantly higher concentrations of ∑melamine than those of urban and background (forest) soils (92.5 ng/g dw). Our findings suggest that fertilizers are an important source of melamine and Cyanuric Acid in farm soils. Spatial distribution of melamine and Cyanuric Acid in soils showed the highest concentrations in eastern China, which corresponded well with population density, industrial, and agricultural activities. An ecological hazard assessment was performed of melamine in soils through a hazard quotient (HQ) approach. The mean HQ value was 0.35, and 7 of 98 surface soils had values above 1. Further studies are needed to discern uptake of melamine and its derivatives by crops and the fate of these chemicals in agricultural ecosystems
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Inter-day and inter-individual variability in urinary concentrations of melamine and Cyanuric Acid
Environment international, 2018Co-Authors: Hongkai Zhu, Kurunthachalam KannanAbstract:Abstract Melamine is used extensively in household products, such as furniture, dinnerware, and food utensils. Several studies have shown that melamine adversely affects kidney function. Nevertheless, little is known about urinary melamine concentrations, and its temporal variability. In this study, 213 first-morning-void urine samples were collected from 19 volunteers for over a month to assess longitudinal variability in concentrations of melamine and its three structural analogues, i.e., Cyanuric Acid, ammeline, and ammelide. Target analytes were found in all urine samples at mean concentrations of 3.3, 16, 0.99, and 0.62 ng/mL, for melamine, Cyanuric Acid, ammelide, and ammeline, respectively. Cyanuric Acid was the major compound found in all urine samples, accounting for 74–80% of the total concentrations, followed by melamine (12–20%), ammelide (4–6%), and ammeline (2–4%). Gender- and age-related differences in melamine concentrations were observed, although no such pattern was found for Cyanuric Acid. After adjusting for creatinine, melamine and Cyanuric Acid concentrations were moderately predictable with inter-day intraclass correlation coefficients (ICCs) in the range of 0.541–0.763. Nevertheless, substantial inter-individual variation in melamine levels existed even after creatinine adjustment, as evidenced by low ICCs (0.008–0.108). Cumulative daily intake of melamine and Cyanuric Acid was calculated on the basis of urinary concentrations and the mean values were found to be at least 10-fold below the current tolerable daily intake.
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Melamine and Cyanuric Acid exposure and kidney injury in US children.
Environmental research, 2018Co-Authors: Sheela Sathyanarayana, Kurunthachalam Kannan, Joseph T. Flynn, Mary Jo Messito, Rachel S. Gross, Kathryn B. Whitlock, Rajendiran Karthikraj, Debra J. Morrison, Maryann L. Huie, Dimitri A. ChristakisAbstract:Abstract Background Melamine and Cyanuric Acid, which are currently used in a variety of common consumer products and present in foods, have been implicated in the development of urolithiasis and acute kidney injury in Chinese children. To determine whether US children have measurable concentrations of these chemicals in their bodies and whether they are at greater risk of acute kidney injury, we measured melamine and Cyanuric Acid exposure in a cohort of US children and determined their relationship with markers of kidney injury. Methods We measured urinary melamine and Cyanuric Acid in a convenience sample of 109 children (4 months – 8 years) from Seattle, WA and New York City, NY using liquid chromatography with tandem mass spectrometry. We measured several urinary markers of kidney injury: fatty Acid binding protein 3 (FABP3), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL) using Luminex xMAP methods, and urine urea was measured using standard laboratory methods. We described urinary melamine and Cyanuric Acid concentrations and assessed predictors of the exposures. We used multivariable linear regression to assess relationships between melamine/Cyanuric Acid and kidney injury markers in unadjusted and adjusted (creatinine, age, sex) analyses. Results Melamine and Cyanuric Acid were above the limit of detection (LOD) in 78% and 95% of all samples, respectively. The mean concentrations (SD) for melamine and Cyanuric Acid were 27.4 ng/ml (141.9 ng/ml) and 35.3 ng/ml (42.4 ng/ml). In unadjusted analyses, we observed statistically significant increases in the percentages of FABP3 and KIM1 in relation to a one log unit change in melamine and Cyanuric Acid, respectively. In adjusted analyses, we observed a 55% (95% CI 0, 141) increase in KIM1 in relation to a one log unit increase in Cyanuric Acid. Conclusions US children have detectable concentrations of melamine and Cyanuric Acid in urine, and these concentrations are higher than those reported in children from other countries. This is a novel finding that improves upon previous exposure estimates using questionnaires only and suggests widespread exposure in the population. Cyanuric Acid is associated with increased KIM 1 concentrations, suggesting kidney injury. Given the potential widespread exposure, future analyses should examine melamine and Cyanuric Acid in relation to chronic kidney disease and markers of kidney injury in a larger cohort that is representative of the general population.
