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EC number: 200-273-8 | CAS number: 56-41-7
- 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
Endpoint summary
Administrative data
Description of key information
Information on repeated oral dose toxicity was gathered by read-across from L-alanyl-L-glutamine.
A subchronic oral toxicity guideline study of L-alanyl-L-glutamine (L-AG) with rats was conducted for 90 days. No treatment-related significant or toxicologically relevant findings were observed. All data from the oral route of administration suggest that they sufficiently cover the dermal and inhalative routes.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 283 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- GLP guideline study with Klimisch Code 2.
Repeated dose toxicity: inhalation - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Read-across was performed from studies for a dipeptide containing L-alanine (L-alanyl-L-glutamine) as well as for DL-alanine.
The pharmacokinetic behaviour of L-alanyl-L-glutamine (L-AG) justifies the approach of read-across from L-AG to L-alanine. Dipeptides such as L-AG are readily degraded into constituent amino acids during transport from the small intestine (Minami et al., 1992; Herzog et al., 1996; Klassen et al., 2000). Levels of alanine and glutamine in blood rise within 15–30 min of oral administration to both rats (Rogero et al., 2006) and humans (Klassen et al., 2000).
The above described toxicokinetic behaviour results in findings from toxicity studies. A subchronic oral toxicity guideline study of L-alanyl-L-glutamine (L-AG) with rats was conducted for 90 days. No treatment-related significant or toxicologically relevant findings were observed. The no observed adverse effect level (NOAEL) was determined to be a dietary dose of 5.0% (3129 mg/kg bw/day in males and 3601 mg/kg bw/day in females) under the present experimental conditions.
From the NOAEL of 3129 mg/kg bw/day determined for the dipeptide Ala-Gln, an oral NOAEL of 1283 mg/kg bw/day can be derived for L-alanine using the ratio of the molecular weights.
The mean human daily intake of alanine for all life stage and gender groups from food and supplements is approximately 3.6 g/d (Food and Nutrition Board, 2005). A dietary dose of 5.0% L-alanine is equivalent to about 25 times amount of the mean daily oral intake for humans.
Other studies indicate that repeated dietary doses of 20% DL-alanine for 26 weeks or 5.0% L-alanine for 3 weeks cause no adverse effects on rats. This supports the findings of the key study. Read-across from DL-alanine to L-alanine was applied because of the structural similarity of racemic alanine to the enantiomer L-alanine.
Citations:
Minami, H., Morse, E., Adibi, S.A., 1992. Characteristics and mechanism of glutamine dipeptide absorption in human intestine. Gastroenterology 103 (1), 3–11.
Birgit Herzog, Brigitte Frey, Karin Pogan, Peter Stehle, Peter Fürst (1996). In vitro peptidase activity of rat mucosa cell fractions against glutamine-containing dipeptides. J. Nutr. Biochem. 7, 135–141.
Petra Klassen, Manolo Mazariegos, Noel W. Solomons and Peter Fürst. The Pharmacokinetic Responses of Humans to 20 g of Alanyl-Glutamine Dipeptide Differ with the Dosing Protocol but Not with Gastric Acidity or in Patients with Acute Dengue Fever. Journal of Nutrition. 2000; 130: 177-182.
Rogero MM, Tirapegui J, Pedrosa RG, Castro IA, Pires IS. Effect of alanyl-glutamine supplementation on plasma and tissue glutamine concentrations in rats submitted to exhaustive exercise. Nutrition. 2006 May; 22(5): 564-71. Epub 2006 Feb 10.
Food and Nutrition Board (2005): Dietary reference intakes for energy, carbohydrate, fiber, fatty acids, cholesterol, protein, and amino acids (macronutrients). Washington DC, National Academic Press
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Key study.
Justification for classification or non-classification
Based on the results of a subchronic 90-day study for a dipeptide containing L-alanine (L-alanyl-L-glutamine) and of supporting studies, L-alanine is not classified for repeated dose toxicity according to DSD and CLP.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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