L-alanine

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitization is the process following the epicutaneous application of a substance to the skin which results in an immunological response specific for this substance. Skin sensitisation is also called "delayed contact hypersensitivity", "contact hypersensitivity", "contact allergy" or "allergic contact dermatitis".

To behave as a contact allergen, a substance must penetrate into the skin and react with proteins. L-alanine is a normal constituent in living cells occurring as a free amino acid, bound to RNA and incorporated in proteins and peptides. Therefore, it is highly improbable that L-alanine acts as a skin sensitizing agent.

Further L-alanine is used in parenteral nutrition, as a dietary supplement, in biochemical research, in cell culture media, as feed additive and is a component found in skin and hair cosmetics.

Based on the available information, there is no human or animal data that indicates L-alanine to be a skin sensitiser. Considering the extensive, widespread dermal exposure to L-alanine in preparations repeatedly applied to the skin, the absence of case reports of humans showing skin reactions is consistent with L-alanine having a very low skin sensitisation potential.

Structural alerts for skin sensitisation were derived in a database which classified as strong or moderate sensitizers. These were the chemicals which would be classified according to the criteria of the Dangerous Substance Directive 67/548/EEC. For the identification of structural alerts, the chemicals were divided into groups, on the basis of reaction mechanisms or by empirical derivation: a) acylating agents; b) alkylating/arylating agents, c) "Michael" electrophiles and precursors; e) free radical generators; d) aldehydes and precursors, f) "thiol-exchange" agents; and g) others (empirical). Forty rules (structural alerts were identified from these group of chemicals. (see: de Silva et al, 1996; Klaschka and Voßmann, 1994).

L-alanine does not contain any of this structural alerts in its chemical structure.

L-tert-Leucine was tested for skin sensitisation by using the guinea pig maximization test. The substance was non-sensitising to the skin of guinea pigs. L-tert-Leucine and L-alanine have similar physico-chemical properties (log Kow, water solubility) and both substances contain

the same functional groups (indicating no peptide reactivity).Therefore, the amino acid L-tert-Leucine should be applicable for read-across purposes. The results for L-tert-Leucine provide further evidence that L-alanine is not a sensitizer.

In another GLP guideline study according to OECD 429 L-valine and L-isoleucine were not able to act as a skin sensitizer when applied to mice at dose levels up to 25 %. L-valine, L-alanine and L-Isoleucine have similar physico-chemical properties (log Kow, water solubility) and all substances contain the same functional groups (indicating no peptide reactivity).Therefore, the amino acids L-valine and L-isoleucine should be applicable for read-across purposes. The results for L-valine an L-Isoleucine provide further evidence that L-alanine is not a sensitizer.

In accordance with REACH Annex XI No. 8.3. column 1 the assessment of this endpoint shall comprise as the first step an assessment of the available human, animal and other data. These data reveal that in vivo testing is not required in accordance with REACH and animal welfare.

Citations:

de Silva D. et al (1996): Alternative Methods for Skin Sensitisation testing. The report and recommendations of ECVAM Workshop 19. ATLA 24, 683 - 705

Klaschka F. und Voßmann D. (1994): Kontaktallergene. Erich-Schmidt-Verlag, Berlin

Migrated from Short description of key information:
L-Alanine is a normal constituent in living cells. L-Alanine cannot be regraded as a skin sensitizing agent.
There is weight of evidence from studies with L-tert-Leucine, L-valine and L-isoleucine in which the amino acids showed to be non-sensitizing.

Justification for selection of skin sensitisation endpoint:
Waiving arguments together with the studies 93-0029-DNT and V6496_2005 provide weight of evidence for endpoint conclusion

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

From experience of the handling of L-alanine in industrial and commercial surroundings, L-alanine is not sensitising via the respiratory route. Studies on this endpoint are not available.

Migrated from Short description of key information:
From experience L-alanine is not sensitising via the respiratory route.

Justification for classification or non-classification

L-alanine is considered as non sensitising and does not trigger respective classification.