Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

There are no data on skin sensitisation available for Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7). In accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5 read-across from appropriate substances is conducted to fulfill the standard information requirements set out in Regulation (EC) No 1907/2006, Annex VII, 8.3.

According to Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across) “to avoid the need to test every substance for every endpoint”.

 

Fatty acids, C16-18, 2-hydroxyethyl esters is an UVCB substance comprised of mainly mono- and diesters of ethylene glycol conjugated with C16 and C18 fatty acids. Thus, the test substance represents a glycol ester, which in general is known to be stepwise hydrolysed by gastrointestinal enzymes into the free fatty acid components and the respective alcohol (Long, 1958; Lehninger, 1970; Mattson and Volpenhein, 1972). Considering the common metabolism, the read-across approach is based on the presence of common precursors and the likelihood of common breakdown products via biological processes that result in structurally similar chemicals, and on common functional groups, structural similarities and similar physico-chemical, toxicological and toxicokinetic behaviour. For further details on the read-across approach, please refer to the analogue justification in section 13 of the technical dossier.

 

As no data are available on skin sensitization of Fatty acids, C16-18, 2-hydroxyethyl esters, read-across to reliable data on the analogue substance Ethylene distearate (CAS 627-83-8) was conducted. To support the read-across data, QSAR predictions were performed with the target substance Fatty acids, C16-18, 2-hydroxyethyl esters (CAS 97281-23-7) using the OECD QSAR Toolbox v3.3.

 

CAS 627-83-8

The skin sensitising potential of ethylene distearate (CAS 627-83-8) was tested according to a Buehler test protocol similar to OECD guideline 406 in Pirbright guinea pigs (Müller, 1982). The solid test material was mixed with a few drops of water and applied at a concentration of 100% for epidermal induction and challenge. The negative control group was treated with the vehicle only. No positive control data was included in the study report for reliability check. At challenge, the neat test substance induced no skin effects in the test and negative control group. No further skin reactions after induction and challenge were observed.

 

In summary, based on the available data, ethylene distearate is not considered to exhibit sensitizing properties.

 

CAS 97281-23-7

QSAR predictions based on the OECD QSAR Toolbox v3.3 were performed with four representative components of Fatty acids, C16-18, 2-hydroxyethyl esters including the C16 and C18 mono-and diester compounds (Dr. Knoell Consult, 2016). The predicted skin sensitisation potential based on protein binding potential was modelled in the OECD QSAR Toolbox v3.3. No alerts for protein binding were found according to Protein binding by OASIS v1.3, Protein binding by OECD and Protein binding alerts for skin sensitisation v1.3.

Based on these results, especially considering the results of the skin sensitizing relevant profiler, OASIS v1.3 (endpoint specific), Fatty acids, C16-18, 2-hydroxyethyl esters is not expected to exhibit skin sensitizing properties.

 

Conclusion on skin sensitising properties

The available experimental data did not indicate a sensitising potential of the structural analogue substance ethylene distearate. The QSAR predictions performed with representative components of the target substance Fatty acids, C16-18, 2-hydroxyethyl esters revealed no alerts for protein binding indicative of skin sensitizing properties in the OASIS v1.3 database. Thus, Fatty acids, C16-18, 2-hydroxyethyl esters is not considered to be a skin sensitiser.

 

 

References

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within the CSR.


Migrated from Short description of key information:
Skin sensitisation (OECD 406): not sensitising (RA CAS 627-83-8)
Skin sensitisation (QSAR): not predicted to be sensitisng (CAS 97281-23-7)

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable study based on the identified similarities in structure and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.