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EC number: 206-058-5 | CAS number: 298-12-4
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Exposure related observations in humans: other data
Administrative data
- Endpoint:
- exposure-related observations in humans: other data
- Type of information:
- other: Litearture data
- Adequacy of study:
- other information
- Rationale for reliability incl. deficiencies:
- other: Literature data
Data source
Reference
- Reference Type:
- publication
- Title:
- Hydroxyproline ingestion and urinary oxalate and glycolate excretion
- Author:
- Knight J., Jiang J., Assimos D.G., Holmes R.P.
- Year:
- 2 006
- Bibliographic source:
- Kidney International , 70, 1929-1934
Materials and methods
- Type of study / information:
- Hydroxyproline ingestion and urinary oxalate and glycolate excretion
- Principles of method if other than guideline:
- Endogenous synthesis of oxalate is an important contributor to calcium oxalate stone formation and renal impairment associated with primary hyperoxaluria. Although the principal precursor of oxalate is believed to be glyoxylate, pathways in humans resulting in glyoxylate synthesis are not well defined. Hydroxyproline, a component amino acid of collagen, is a potential glyoxylate precursor.
The contribution of dietary hydroxyproline derived from gelatin to urinary oxalate and glycolate excretion was investigated. - GLP compliance:
- not specified
Test material
- Reference substance name:
- Glyoxylic acid
- EC Number:
- 206-058-5
- EC Name:
- Glyoxylic acid
- Cas Number:
- 298-12-4
- Molecular formula:
- C2H2O3
- IUPAC Name:
- 2-oxoacetic acid
Constituent 1
Method
- Ethical approval:
- not specified
- Details on study design:
- Subject:
Healthy subject with no history of nephrolithiasis were recruited from Wake Forest University Medical Center. Subjects were not taking any medications or dietary supplements and refrained from vigorous exercise.
Gelatin/whey study:
Ten subjects (five male and five female subjects; mean age, 32 ± 4 years; age rang, 28-39 years) participated in the study. Subjects were initially asked to collect three consecutive 24 h urines while consuming self-selected diets. On the last 2 days of this portion of the study, blood was drawn 4 h after breakfast. Following these collectiosn, subjects consumed diets controlled in its content of calories, fat, protein, carbohydrate, calcium, magnesium, sodium, phosphorus, and oxalate for two 5-day periods separated by at least a 1-week washout period. During one 5-day period, the diet contained a quarter of its protein as gelatin. The second 5-day period of the diet contained a quarter of its protein as whey. The hydroxyproline content of the gelatin measured by AAA Laboratory was 9.17 g /100 g, and the whey protein was free of hydroxyproline.
Each diet contained 15-16% protein, 29-30% fat, and 54-55% carbohydrate. To closely control the volume of urine, subjects drank only the fluids provided, which included 2 L of bottled water/day.
Sodium, calcium, magnesium, phosphate, uric acid, citrate, and urea were measured in urine samples.
Gelatin-loading studies:
Six subject (three male and three female subjects; mean age 28 ± 7 years; age rang, 23-42 years) were recruited for this study to investigate the effect of varying gelatin loads on glycolate and oxalate in plasma and urine, and the time course of metabolism of hydroxyproline over 24 h following a 10 g gelatin load. Through this study, subjects wee on self-selected diets, but were required to avoid oxalate-rich foods and eat moderate amounts of protein and calcium. The day before each load, subjects fasted overnight (14 h). A fasting 2 h urine collection was obtained with a blood sample at the midpoint of this collection. Urine was collected for 6 h and blood was drawn 3 h after ingestion of each load. The time course of changes in plasma hydroxyproline, oxalate, and glycolate levels and the urinary excretion of oxalate and glycolate were examined on a d 10 g load. Four sequential 2 h urine collections were obtained after the 10 g load together with a blood sample at the midpoint of each collection. Over the next 16 h, subjects obtained an evening collection (6 h) and another in the morning of the following day (10 h). Subject were required to drink 250 mL bottled water/h over the 6-h period following gelatin loads, and the initial 8-h period after the 10 g load to ensure good urine output.
Plasma and urine analysis:
Blood samples were obtained by venipuncture into heparinized tubes and immediately centrifuged at 4°C for 10 min.
Plasma was filtered using acid washed Ultrafree-MC centrifugal filters with a 10 000 nominal molecular weight limit. Twenty-four urine collections were collected in boric acid. For oxalate analysis, urines were diluted in 2 mM HCl before storage at -80°C. Total urine oxalate and plasma oxalate were determined by ion chromatography.
Statistical analyses:
Resulst are presented as mean values ± s.d, unless otherwise indicated. The statistical significance of results was assessed by analysis of variance and considered significant if P-values were 0.05 or less. The Holm-Sidak method was used to correct for multiple comparisons and all assays were conducted using SigmaStat. - Exposure assessment:
- measured
Results and discussion
- Results:
- Responses to the ingestion of 30 g of gelatin or whey protein were compared on controlled oxalate diets. The time course of metabolism of a 10 g gelatin load was determined as well as the response to varying gelatin loads. Urinary glycolate excretion was 5.3-fold higher on the gelatin diet compared to the whey diet and urinary oxalate excretion was 43% higher. Significant changes in plasma hydroxyproline and urinary oxalate and glycolate were observed with 5 and 10 g gelatin loads, but not 1 and 2 g loads. Extrapolation of these results to daily anticipated collagen turnover and hydroxyproline intake suggests that hydroxyproline metabolism contributes 20-50% of glycolate excreted in urine and 5-20% of urinary oxalate derived form endogenous synthesis. Result also revealed that the kidney absorbs significant quantities of hydroxyproline and glycolate, and their metabolism to oxalate in this tissue warrants further consideration
Applicant's summary and conclusion
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