L-proline

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-proline is a normal constituent in living cells occurring as a free amino acid, bound to RNA and incorporated in proteins and peptides. Therfore, it is highly improbable that L-proline acts as a skin sensitizing agent.

Further, L-proline is used in parenteral nutrition, as a dietary supplement, in biochemical research, in cell culture media, as a feed additive, as an excipient in medicinal products and is a component found in skin cosmetics.

Based on the available information, there is no human or animal data that indicates L-proline to be a skin sensitiser. Considering the extensive, widespread dermal exposure to L-proline in preparations repeatedly applied to the skin, the absence of case reports of humans showing skin reactions is consistent with L-proline 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-proline does not contain any of this structural alerts in its chemical structure.

Absence of skin sensitizing properties is supported by a result with L-valyl-L-proline which was tested for skin sensitisation by using the guinea pig maximization test. The substance was non-sensitising to the skin of guinea pigs. L-valyl-L-proline and L-proline have similar physico-chemical properties (logKow, water solubility) and both substances contain the same functional groups (indicating no peptide reactivity). Further, L-valyl-L-proline has a higher log Kow which makes it more probable that this substance overcomes the lipophilic stratum corneum which is the major barrier to the penetration of hydrophilic compounds into and through the skin. In adition cutaneous metabolism results in the constituent amino acids. Therefore, the dipeptide should be applicable for read-across purposes. This result provides further evidence that L-proline 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-proline is a normal constituent in living cells. L-proline cannot be regarded as a skin sensizing agent.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

From experience L-proline is not sensitising via the respiratory route. Studies on this endpoint are not available.

Migrated from Short description of key information:
From experience of the handling of L-proline in industrial and commercial surroundings, L-proline is not sensitising via the respiratory route.

Justification for classification or non-classification

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