Dehydrated sorbitol, C18 (unsaturated) fatty acid esters, ethoxylated

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Skin sensitisation

Justification for grouping of substances and read-across

There are no data available on the skin sensitisation potential of Sorbitan monooleate, ethoxylated (1-6.5 moles ethoxylated). In order to fulfil the standard information requirements set out in Annex VIII, 8.3., in accordance with Annex XI, 1.5., of Regulation (EC) No 1907/2006, read-across from the structurally related substance sorbitan monolaurate, ethoxylated (CAS 9005-64-5, poylsorbat 21) was conducted.

In accordance with 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).

The test substance Sorbitan monooleate, ethoxylated (1-6.5 moles ethoxylated) represents an UVCB substance composed of polyethoxylated sorbitan esterified mainly with C18 unsaturated fatty acids (>60 - 100%). The structurally related substance sorbitan monolaurate, ethxylated (polysorbat 21, CAS 9005-64-5) is considered as structural analogue substance due to structural similarities, the presence of common functional groups and the likelihood of common breakdown products: Sorbitan monooleate, ethoxylated (1-6.5 moles ethoxylated) and sorbitan monolaurate, ethoxylated (poylsorbat 21) are polyethoxylated sorbitan esters linked to oleate or laurate, with ethoxylation degrees of 3 – 5 or 1 -7 EO respectively.

Target and source substance are polyethoxylated sorbitan esters, also called polysorbates, which are known to be hydrolysed after oral ingestion at the ester link by pancreatic lipase resulting in the fatty acid moiety and the polyethoxylated sorbitan moiety (CIR, 1984; EPA, 2005; Fruijitier-Pölloth, 2005). Depending on the route of exposure, esterase-catalysed hydrolysis takes place at different places in the organism: After oral ingestion, polysorbates will undergo chemical changes already in the gastro-intestinal fluids as a result of enzymatic hydrolysis. In contrast, substances which are absorbed through the pulmonary alveolar membrane or through the skin enter the systemic circulation directly before entering the liver where hydrolysis will basically take place. 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. The C2 units are cleaved as acyl-CoA, the entry molecule for the citric acid cycle. 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 second cleavage product, the polyethoxylated sorbitan moiety, is expected to be excreted mostly in the feces and to a minor amount in the urine without further metabolism (CIR, 1984; EPA, 2005; Fruijitier-Pölloth, 2005). Based on the common metabolic fate of polyethoxylated 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.

Discussion

Skin sensitisation

CAS 9005-64-5: Animal data

As Sorbitan monolaurate, ethoxylated (1 - 7 EO, polysorbat 21, CAS 9005-64-5) represents a surfactant, a guinea pig maximisation test according to Magnusson and Kligman was conducted (Notox, 2012). The study was performed according to OECD 406 under GLP conditions with the following concentrations of the test substance dissolved in corn oil: 2% for intradermal induction, 100% for epidermal induction and challenge. At challenge, the test substance at 100% induced no effects in test and control group animals. The positive control (20% alpha-hexyl cinnamic acid) induced the expected results. Thus, under the conditions of this test, the test substance was not a skin sensitiser.

CAS 9005-65-6 (Sorbitan monooleate, ethoxylated (Tween 81[5EO]): Observations in humans

The skin sensitising effects of Tween 81 was investigated in a human patch test (Schwartz 1959). Fifty volunteers were exposed to the undiluted test substance under occlusive conditions initially for 3 days and in a challenge 7 days after removal of the initial patch. At the end of the 72-h exposure period in the challenging application, no reactions on the skin in any of the subjects were observed. Therefore, the substance was not considered to be a skin sensitiser.

A further human patch test is available, in which 10 human subjects were exposed to the test substance at a concentration of 12% under occlusive conditions initially for 5 days and in a challenge 10 days after removal of the initial patch (Durfee, 1943). At the end of the 48-h exposure period in the challenging application, no reactions on the skin in any of the subjects were observed. Consistent with the results of the above study, no skin sensitising effects were observed in any of the human volunteers exposed to the test substance.

However, these data alone are not sufficient for risk assessment of this endpoint due to the limited details on experimental methods and results.

 

Conclusions for skin sensitisation

No reliable animal studies assessing the skin sensitising properties of Sorbitan monooleate, ethoxylated (1-6.5 moles ethoxylated) are available. A guinea pig maximisation test according to Magnusson and Kligman was performed with the analogue substance sorbitan monolaurate, ethoxylated (poylsorbat 21, 1 - 7 EO, CAS 9005-64-5), in which no skin sensitisation was induced (Notox, 2012).

In support of these results, human data are available for the test substance itself, showing no sensitising effects on the skin of human volunteers.

Taking all data into consideration, Sorbitan monooleate, ethoxylated (1-6.5 moles ethoxylated) is not considered to be a skin sensitiser.

References (not included in IUCLID):

CIR (1984). Final Report on the Safety Assessment of Polysorbat 20, 21, 40, 60, 61, 65, 80, 81 and 85. Journal of the American College of Toxicology, 3(5): 1- 82

 

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

EPA (2005). ACTION MEMORANDUM. Reassessment of six inert ingredient exemptions from the requirement of a tolerance. United States Environmental Protetio Agency, ashington, D.C. 20460

 

Fruijitier-Pölloth (2005). Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products.Toxicology 214, 1 - 38

 

Migrated from Short description of key information:
skin sensitisation (OECD 406): no skin sensitising effects (CAS 9005-64-5, sorbitan monolaurate, ethoxylated; polysorbat 21 [1 - 7EO])
skin sensitisation (observations in humans): no skin sensitising effects (CAS 9005-65-6, Sorbitan monooleate, ethoxylated; Tween 81 [5EO])

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is an 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

Additional information:

Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

Based on substance-specific data and read-across from a structurally similar substance, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.