Registration Dossier

Administrative data

Description of key information

The overall assessment of the available information gave no indication for sensitising properties of the category members.

Key value for chemical safety assessment

Skin sensitisation

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

No data are available for the substance therefore data on a category substance -Didodecyl fumarate (CAS 2402-58-6)are used for the assessment of skin sensitisation. This substance was selected for testing, because it represents the category member with the shortest fatty alcohol side chain, and consequently with the lowest molecular weight, which is regarded as worst-case approach in terms of hazard assessment of the PFAE fumarates for the local as well as for systemic effects.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Section 13) and within Chapter 5.1 of the CSR.

Skin sensitisation

There is a reliable GLP guideline study (OECD 442B, Höger, 2013) in order to assess the skin sensitising potential of Didodecyl fumarate (CAS 2402-58-6). In this local lymph node assay five female CBA mice per group were tested with the test item at concentrations of 10, 25 and 50 % (w/w) in the vehicle methyl ethyl ketone (MEK). The animals did not show any signs of systemic toxicity or local findings during the course of the study and no cases of mortality were observed. In the positive control (alpha-hexylcinnamaldehyde) scaling and incrustations were observed. A statistically significant or biologically relevant increase in ear weights was not observed in any treated group in comparison to the vehicle control group. Furthermore, the cut-off-value for a positive response regarding the ear weight (25 % increase) was not exceeded in any dose group.

A test item is regarded as a sensitizer in the LLNA if exposure to one or more test item concentration results in a 1.6-fold or greater increase in incorporation of BrdU compared with concurrent controls, as indicated by the Stimulation Index (S.I.). The estimated test item concentration required to produce a S.I. of 1.6 is referred to as the EC1.6 value. In this study Stimulation Indices (S.I.) of 1.2, 0.9 and 0.9 were determined with the test item at concentrations of 10, 25 and 50 % (w/w) in MEK. An unusual dose response was observed. An EC1.6 value could not be determined as all S.I. obtained were below the threshold of 1.6.

A statistically significant or biologically relevant increase in BrdU incorporation and also in lymph node weight, cell count and ear weight measurement was not observed in any of the test item dose groups in comparison to the vehicle control group. Furthermore, the cut off-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was not exceeded in any of the tested dose groups (Ehling et al., 2005).

As expected, a statistical and biological relevant increase in BrdU labelling, lymph node weight, lymph node cell count and ear weight measurement was determined in the positive control.

The test item was thus not a skin sensitiser under the test conditions of this study.

 

Conclusion for sensitisation

An in-vivo skin sensitisation study was performed using Didodecyl fumarate (CAS 2402-58-6), showing no potential for skin sensitisation. As dermal absorption is expected to decrease with increasing fatty alcohol chain length, Didodecyl fumarate (CAS 2402-58-6) the category member with the shortest fatty alcohol side chain and thus lowest log Pow, represents a worst-case within the category. 

In conclusion, the available data indicate that no hazard for skin sensitisation for any category member has to be expected.

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the group concept is applied to the members of the PFAE fumarate category, data will be generated from representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled on this basis.

Therefore, based on the group concept, all available data on sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 and the substance is not classified as a skin sensitiser.