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:

Sensitisation

Justification for read-across

There are no data on sensitisation available for Fatty acids, rape-oil, mixed esters with 1,4:3,6-dianhydro-d-glucitol, sorbitan and sorbitol. 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 VIII, 8.5.

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, rape-oil, mixed esters with 1,4:3,6-dianhydro-d-glucitol, sorbitan and sorbitol represents an UVCB substance comprised of different Sorbitan fatty acid ester, mainly of mono-, di- and tri-esters of sorbitol, sorbitan and 1,4:3,6-dianhydro-d-glucitol esterified with natural fatty acids with a chain length ranging from of C16 – C20, mostly C18 mono-unsaturated.

 

Sorbitan fatty acid esters are known to be stepwise hydrolysed to the respective fatty acid and the alcohol moiety, which will be present mostly as the open chain isomer D-glucitol depending on the pH (Stryer, 1996). The first cleavage product, the fatty acid, is stepwise degraded by beta-oxidation based on enzymatic removal of C2 units in the matrix of the mitochondria in most vertebrate tissues. For the complete catabolism of unsaturated fatty acids such as oleic acid, an additional isomerization reaction step is required. The alpha- and omega-oxidation, alternative pathways for oxidation, can be found in the liver and the brain, respectively (CIR, 1987). The alcohol residue, mostly D-glucitol, is absorbed from the gastro-intestinal tract and can be metabolized by the intestinal microflora (Senti, 1986) or in the liver (Touster, 1975). Based on the common metabolic fate of Sorbitan fatty acid esters, the read-across approach is based on the presence of common functional groups, common precursors and the likelihood of common breakdown products via biological processes, which result in structurally similar chemicals and hence exhibit similar 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 sensitizing properties of Fatty acids, rape-oil, mixed esters with 1,4:3,6-dianhydro-d-glucitol, sorbitan and sorbitol , read-across to reliable data on the analogue substance Anhydro-D-glucitol trioleate (CAS 26266-58-0) was conducted.

 

CAS 26266-58-0

A guinea pig maximisation test was performed with Anhydro-D-glucitol trioleate (Sorbitan trioleate) according to OECD guideline 406 under GLP conditions (Phycher Bio Developpment 2012). The test substance was applied in olive oil for intradermal induction at a concentration of 2%, at 100% for epidermal induction and at 50 and 100% for challenge and rechallenge, respectively. At challenge, irritation was observed in almost all animals of the negative control group. Therefore, only reactions in the test group that exceeded the most severe reactions seen in the control group were attributed to skin sensitisation. Hence, no sensitisation reaction was noted in animals from the treated group with the test item at 50 and 100%. In view to clarify these results, a rechallenge phase was performed with the test item diluted at 25 and 50%. No effects were then observed in the negative control group. In the test group challenged with 25 and 50% test substance, 10 and 20% of the animals, respectively, showed a positive reaction 24 h after rechallenge. After 48 h, 10% of the animals treated with 50% test substance during the rechallenge phase showed a positive reaction. The positive control (6.25 and 12.5% alpha-hexylcinnamaldehyde) induced the expected result. Based on these results, Anhydro-D-glucitol trioleate (Sorbitan trioleate) was considered not to be sensitising.

 

 

Human data

In addition to the available data on Anhydro-D-glucitol trioleate (Sorbitan trioleate) on sensitization in guinea pigs, human data are available for the read-across substances Anhydro-D-glucitol trioleate (Sorbitan trioleate), Sorbitan, (Z)-9-octadecenoate (2:3) and for Sorbitan laurate. Due to limited documentation, the data are considered as not assignable and are therefore not taken into account for hazard assessment.

 

CAS 26266-58-0

2 human patch tests are available for Anhydro-D-glucitol trioleate: The undiluted test substance was initially applied to the skin of 50 volunteers for 3 days. 7 days after removal of the test substance, challenge occurred for additional 3 days. 50 volunteers were included as respective negative control group. No sensitising effects were observed (Schwartz 1959). Furthermore, Anhydro-D-glucitol trioleate failed to induce sensitizing reactions to the skin in 10 volunteers treated with 30% test substance applied to 10 volunteers in an epicutaneous patch test (Durfee 1946).

 

CAS 8007-43-0

For Sorbitan, (Z)-9-octadecenoate (2:3) human data on sensitisation is available. A human patch test was performed with 50 volunteers under occlusive conditions. The undiluted test substance was initially applied for 3 days and a challenging application for 3 days was done 7 days after removal of the initial patch. None of the volunteers showed a sensitisation reaction to Sorbitan, (Z)-9-octadecenoate (2:3) (Schwartz 1959).

 

In 2002, Uniqema performed a study, investigating a 30% aqueous dispersion in 10 volunteers under occlusive conditions for an initial application of 5 days and a challenge of 2 days after a 10-day induction period. No reaction occurred among the 10 participants following either the first or second application of the test substance. This indicates that the substance is not a skin sensitiser (Uniqema 2002). Hence, based on human data, Sorbitan, (Z)-9-octadecenoate (2:3) does not exhibit skin sensitizing properties.

 

CAS 1338-39-2 

For the analogue substance Anhydro-D-glucitol trioleate, two human patch tests are available performed with a test substance concentration of 50%. In detail, 50 volunteers were initially treated for 3 days and challenged for 3 days, 7 days after removal of the initial patch. No sensitising effects were observed (Schwartz 1959). Likewise, a patch test with 30% test substance applied to 10 volunteers induced no sensitising potential (Durfee 1946).

 

CAS 1338-43-8

Further, a human patch test is available for Sorbitan laurate in which 50 volunteers were treated with the test substance under occlusive conditions for 72 h (Schwartz, 1959). One week later, patches were re-applied for 72 hours; followed by scoring of the sensitising effects. No sensitising effects were noted in the volunteers.

Overall conclusion for skin sensitisation

Based on reliable animal data, the structural analogue substance Anhydro-D-glucitol trioleate is not considered as skin sensitising. Hence, Fatty acids, rape-oil, mixed esters with 1,4:3,6-dianhydro-d-glucitol, sorbitan and sorbitol are not expected to exhibit skin sensitizing properties.

 

References

CIR (1987). Final report on the safety assessment of oleic acid, lauric acid, palmitic acid, myristic acid, stearic acid. J. of the Am. Coll. of Toxicol.6 (3): 321-401

 

Senti, F.R. 1986. Health aspects of sugar alcohols and lactose. Contract No. 223-83-2020, Center for food safety and applied nutrition, Food and Drug Administration, Dept. of Health and Human Services, Washington, DC 20204, USA

 

Stryer, L. 1996. Biochemie. Spektrum Akademischer Verlag; Auflage: 4th edition

Suldano, S., Gramenzi, F., Cirianni, M., Vittozzi, L. (1992): Xenobiotic-metabolizing enzyme systems in test fish - IV. Comparative studies of liver microsomal and cytosolic hydrolases. Comparative Biochemistry and Physiology Part C: Comparative Pharmacology. 101(1), 117-123.

 

Touster, O. 1975: Metabolism and physiological effects of polyols (alditols). In : Physiological effects of food carbohydrates.Washington, DC: American Chemical Society. p 229-239

 


Migrated from Short description of key information:
skin sensitisation (OECD 406): no skin sensitising effects

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. 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

The available data on skin sensitisation of the structural analogue do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

No data on respiratory sensitisation are available.