Registration Dossier
Registration Dossier
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 200-273-8 | CAS number: 56-41-7
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
