Registration Dossier

Administrative data

Description of key information

L-alanine is not be considered to have irritating or corrosive properties to human skin or eye nor to the respiratory system.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Common Read-Across for Skin Irritation/Corrosion and Eye Irritation/Corrosion

 Read-across was performed from studies for a dipeptide containing L-alanine (L-alanyl-L-glutamine) and studies for 3 amino acids (L-valine, L-tert.-leucine, L-isoleucine) with certain features similar to features of L-alanine:

·        L-alanine like L-valine, L-tert. leucine, L-isoleucine is a non-polar natural amino acid.

·        The pH-value of L-alanine like that of L-valine, L-tert.-leucine, L-isoleucine is in the neutral range.

These common features are indications for common properties as to skin irritation/corrosion (ECETOC, 1995) as well as eye irritation/corrosion (ECETOC, 1998) and so to provide WoE.

  

Skin

 L-alanyl-L-glutamine was tested for skin irritation / skin corrosion. The substance was non-irritant to rabbit skin following a single four-hour application. The results provide weight of evidence that L-alanine is non irritant.

  L-tert.-leucine was tested for skin irritation / skin corrosion. The substance was non-irritant to rabbit skin following a single four-hour application. The results provide weight of evidence that L-alanine is non irritant.

The dermal irritant potential of L-valine was assessed by application of the moistened product to the skin of three rabbits in accordance with OECD guideline 404. No signs of irritation were seen at any point after application, thus the product is classified as not-irritating to human skin.

 The dermal irritant potential of L-isoleucine was assessed by application of the moistened product to the skin of three rabbits in accordance with OECD guideline 404. No signs of irritation were seen at any point after application, thus the product is classified as not-irritating to human skin.

 These 4 amino acids do not exhibit a SAR (structural alert or set of fragments) for skin irritation / corrosion (BfR rule base: ECETOC, 1995; Gerner at al., 2004; Walker, 2004; RVIM, 2005) to induce one of the different types of irritant contact dermatitis (ICD). The occurrence of structural analogues that exhibit corrosion (or irritation) potential can be used to predict the effect in the substance of interest and derogate from further assessment, as indicated in the OECD testing strategy for skin irritation/corrosion (OECD, 2001). Negative data from structural analogues may also be used to make predictions in certain cases, provided that there are no other substructures in the substance that are thought likely to cause the effect (ECHA, 2008). This is the case for L-alanine as well as the 3 amino acids to read-across.

  

ECETOC (1995): Technical report No. 66 Skin irritation and corrosion: Reference chemicals data bank. Brussels, 1995

Gerner I., Schlegel K., Walker J.D., Hulzebos, E. (2004). Use of physico-chemical property limits to develop rules for identifying chemical substances with no skin irritation or corrosion potential. QSAR and Combinatorial Science 23, 726-733.

ECHA (2008): Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance.

OECD (2001) OECD Attachment to the Test Guideline 404: A Sequential Testing Strategy for Skin Irritation and Corrosion. OECD, Paris, France.

RIVM (2005): Hulzebos, E., Sijm, D., Traas, T., Posthumus, R., Maslankiewicz, L. (2005) Validity and validation of expert (Q)SAR systems. SAR and QSAR in Environmental Research 16, 385-401.

Walker, J.D., Gerner, I., Hulzebos, E., Schlegel, K. (2004) (Q)SARs for Predicting Skin Irritation and Corrosion: Mechanisms, Transparency and Applicability of Predictions. QSAR & Combinatorial Science 23, 721-725.

 

 Eye

 L-alanyl-L-glutamine was tested for eye irritation / eye corrosion. The substance was non-irritant to rabbit eye following a single application. The substance is not to be classified as an eye irritant according to the criteria of the CLP-regulation (Regulation 1272/2008). The results provide weight of evidence that L-alanine is non irritant.

 The eye irritant potential of L-tert.-leucine was assessed by application of the dry product to the eyes of three rabbits in accordance with OECD guideline 405. The product is classified as not-irritating to the eye.

 The eye irritant potential of L-valine was assessed by application of the dry product to the eyes of three rabbits in accordance with OECD guideline 405. The product is classified as not-irritating to the eye.

 The eye irritant potential of L-isoleucine was assessed by application of the product to the eyes of three rabbits in accordance with OECD guideline 405. The product is classified as not-irritating to the eye.

 The BfR physico-chemical rule base predicts the absence of eye irritation. Evaluations of the BfR rule bases for the prediction of no eye irritation (Tsakovska et al, 2005) have been carried out independently. However, when the absence of irritation cannot be excluded, further information on the structure of the chemical is needed to predict presence of irritation/corrosion.

 The decision support system (DSS) developed by the German Federal Institute for Risk Assessment (BfR) uses physico-chemical exclusion rules to predict the absence of eye irritation/corrosion potential in combination with structural inclusion rules (SARs) to predict the presence of such potential (Gerner et al., 2005).

 L-alanine as well as the 3 amino acids to read-across reveal to be non-irritating to the eye when using this tool. The prediction is supported by the test results which sustains the prediction for L-alanine. Negative data from structural analogues may also be used to make predictions in certain cases, provided that there are no other substructures in the substance that are thought likely to cause the effect (ECHA, 2008). This is the case for L-alanine.

 

 ECETOC (1998): Technical report No. 48 Eye irritation. Reference chemicals data bank (2nd Edition). Brussels, June 1998

Gerner, I., Liebsch, M., Spielmann, H. (2005). Assessment of the Eye Irritating Properties of Chemicals by Applying Alternatives to the Draize Rabbit Eye Test: The Use of QSARs and In Vitro Tests for the Classification of Eye Irritation. Alternatives to Laboratory Animals 33, 215-237.

ECHA (2008): Guidance on information requirements and chemical safety assessment Chapter R.7a: Endpoint specific guidance.

Tsakovska, I., Netzeva, T., Worth AP. (2005). Evaluation of (Q)SARs for the prediction of Eye Irritation/Corrosion Potential -physico-chemical exclusion rules. JRC Report EUR 21897 EN, 42pp. European Chemicals Bureau, Ispra, Italy. Accessible from: http://ecb.jrc.it.

 

 Respiratory System

There are no data available which indicate that L-alanine is irritant to the respiratory system.

 


Justification for selection of skin irritation / corrosion endpoint:
Study 90-0004-DNT together with studies 93-0027-DNT, V 6211/03 and efsa_2010 provide weight of evidence for endpoint conclusion.

Justification for selection of eye irritation endpoint:
Study 90-0005-DNT together with studies 93-0028-DNT, V 6215/14 and efsa_2010 provide weight of evidence for endpoint conclusion.

Justification for classification or non-classification

Read-across provides substantial weight of evidence that L-alanine does not show irritating or corrosive properties both to skin and eye.