Reaction products resulting from the esterification of Sorbitol with C8 – 18 (even) and C18 unsaturated fatty acids in the ratio of 1:1

Carcinogenicity

Description of key information

Based on expert judgment,  there is no evidence that members of the Sorbitan fatty acid esters cause carcinogenicity.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

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 Sorbitan fatty acid esters 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.

Based on expert judgement, a testing proposal for a carcinogenicity study within the Sorbitan fatty acid esters category would be scientifically unjustified.

Additional information

Justification for grouping of substances and read-across

The Sorbitan fatty acid esters category covers fatty series of analogous esters comprised of Sorbitan and natural fatty acids. The category contains UVCB substances, which exhibit differences in chain length (C8-C18), degree of esterification (mono-, di-, tri- and higher esters) and extent of unsaturation (saturated and mono unsaturated).

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, for each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier (see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

In accordance with Column 2 of Annex X, 8.9.1, of Regulation (EC) No 1907/2006, a carcinogenicity study may be proposed by the registrant or may be required by the Agency in accordance with Articles 40 or 41 if: the substance has a widespread dispersive use or there is evidence of frequent or long-term human exposure, and the substance is classified as germ cell mutagen category 2 or there is evidence from the repeated dose study(ies) that the substance is able to induce hyperplasia and/or pre-neoplastic lesions.

There is no evidence that Sorbitan fatty acid esters induce gene mutations in bacteria or chromosome aberrations in mammalian cells, as the results of all genotoxicity studies were consistently negative. Furthermore, in the available repeated dose toxicity studies and developmental studies, no substance-related increases in the incidence of hyperplasia or pre-neoplastic lesions were observed.

The available and relevant studies do not indicate that Sorbitan fatty acid esters fulfil the criteria for classification as germ cell mutagen or that they are able to induce hyperplasia and/or pre-neoplastic lesions. Therefore, the conditions for a carcinogenicity study to be proposed or required set out in Column 2 of Annex X, 8.9.1, are not met. Furthermore, the weight of evidence from all available information leads to the conclusion that Sorbitan fatty acid esters are not carcinogenic. Therefore, a carcinogenicity study is scientifically unjustified, will not be proposed and shall be omitted for reasons of animal welfare in accordance with Annex XI, 1.2, of Regulation (EC) 1907/2006.

Justification for selection of carcinogenicity via oral route endpoint:
No carcinogenicity study is required, since the substance is not mutagenic and no hyperplasia or pre-neoplastic lesions were observed in any of the available studies.

Justification for selection of carcinogenicity via inhalation route endpoint:
No carcinogenicity study is required, since the substance is not mutagenic and no hyperplasia or pre-neoplastic lesions were observed in any of the available studies.

Justification for selection of carcinogenicity via dermal route endpoint:
No carcinogenicity study is required, since the substance is not mutagenic and no hyperplasia or pre-neoplastic lesions were observed in any of the available studies.