Acetic acid, 2,2-difluoro-2-[[2,2,4,5-tetrafluoro-5-(trifluoromethoxy)-1,3-dioxolan-4-yl]oxy]-

Endpoint summary

Description of key information

Skin sensitising properties of F-DIOX acid salt were evaluated through the Read Across approach with cC6O4 ammonium salt.
Two experimental studies were performed on cC6O4 ammonium salt.
It was concluded that F-DIOX acid does not show skin sensitisation properties.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In order to evaluate the skin sensitization properties of F- DIOX acid it was deemed appropriate to use the Read Across approach based on the experimental studies performed on cC6O4 ammonium salt and to apply the same considerations by virtue of similarity of chemical structure between F- DIOX acid and cC6O4 ammonium salt (CAS no: 1190931-27-1).

C6O4 ammonium salt is the carboxylic acid derivative of F-DIOX acid and therefore C6O4 ammonium salt differs from F-DIOX acid only for the presence of the cationic part NH4.

 

In order to evaluate the potential for skin sensitization of cC6O4 ammonium salt, according to column 2 of section 8.3 of Annex VII of REACH Regulation, the LLNA was performed as a first choice on the test item.

The test item cC6O4 ammonium salt is an anionic surfactant classified according to CLP Regulation(REGULATION (EC) No 1272/2008)as Skin Irritant 2.

The LLNA test indicates C6O4 ammonium salt as skin sensitizer under test conditions. Following the criteria reported in the technical report ECETOC 87 (2003), which proposes criteria to classify skin sensitizer according to potency, the result of this test indicates C6O4 as weak sensitizer since an EC3 value of 33.9% was calculated. However, as expressed in the OECD 429 guideline the LLNA may not be suitable to test irritants.

In scientific literature, the fact that irritancy augments the induction response and/or can sometimes lead to non-specific proliferation responses in the LLNA is known (Basketter et al., 2009;Montelius et al., 1998; Woolhiser et al., 1998; Basketter et al., 2007a,b,c). This raises the possibility of false positive results in the original LLNA caused by non-specific cell activation as a result of inflammatory processes in the skin (irritation) (Vohr and Ahr, 2005).

The possibility of false positive findings for irritant substances, including some type of surfactants, is reported in the OECD guideline 429. Mehling et al (2007) reports that for the category of surfactants, which is generally regarded to be without a sensitization, unexpected positive results were observed in LLNA tests. The OECD 429 guideline indicates as limitation the use of LLNA for this category of chemicals.

Basing on the reasonings reported above and according to the OECD 429 guideline, which states it should be recognised that for classes substances that are potential confounders the use of OECD 406 may necessitate, it was deemed necessary to better assess the sensitization potential of C6O4 ammonium salt carrying out a further study.

A Buehler test (OECD 406) was performed in order to get reliable information on skin sensitizer properties of the test substance.

The Buehler (OECD 406) test was performed since the method well reproduces the normal human exposure through dermal contact.

In the Buehler test a net response of 15% incidence is used as the criterion for a chemical being classified as a sensitizer.

C6O4 ammonium salt tested in the Buehler test at the higher non irritant concentration (concentration of 50% in sterile water) both for induction and challenge phases, showed 100% negative results: no response to the test item was apparent at challenge in any animal of the test and control groups. This result indicates the test item is a non sensitizer.

In the light of these results and considering the limitation of LLNA with irritant substances, the LLNA result for C6O4 ammonium salt can be interpreted as a false positive. Therefore it can be affirmed that cC6O4 ammonium salt does not have skin sensitising properties.

 

Considering the similarity of chemical structure between F- DIOX acid and cC6O4 ammonium salt, it can be concluded that the same biological behaviour between F- DIOX acid and cC6O4 ammonium salt is expected.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The registered intermediate F-DIOX acid is a corrosive substance. Considering data on related salt cC6O4 ammonium salt above discussed, according to the criteria reported in the REGULATION (EC) No 1272/2008 (EU Regulation on Classification, Labeling and Packaging of substances and mixtures), F-DIOX acid would not be considered a skin sensitiser.