Oleic acid, monoester with oxybis(propanediol)

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Justification for grouping of substances and read-across

There are no data available on the skin sensitisation potential of Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6). In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances 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).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006 whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

Overview for skin sensitisation

CAS	Skin Irritation/Corrosion
49553-76-6 (a) Target substance	RA: 67707-33-1 RA: 63705-03-3 +QSAR
67707-33-1 (b)	Not sensitising
63705-03-3	Not sensitising

 (a) Substances subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

 (b) Substances that are either already registered under REACh or not subject to the REACh  Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6)

A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Discussion

Skin sensitisation

 

CAS 49553-76-6

The protein binding potential of oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6) was assessed to predict skin sensitisation potential using the OECD QSAR Toolbox, v2.3 (Sica, 2012). The substance was predicted negative for protein binding potential.

Since no studies investigating the skin sensitisation potential of oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6) are available, in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from the structurally related analogue substances glycerides, C14-18 mono- and di- (CAS# 67701-33-1) and 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) was conducted.

CAS 67701-33-1

The skin sensitisation potential of glycerides, C14-18 mono- and di- was tested in an in vitro Direct Peptide Reactivity Assay (DPRA) according to publications of Gerberick et al. (2004 and 2007), Bauch et al. (2010) and Maxwell et al. (2011). In this GLP-study, the reactivity of the test substance towards synthetic cysteine (C)- or lysine (K)-containing peptides was evaluated (Kolle; 2012). Three samples of the test substance at concentrations of 3.76% (corresponding to a theoretical molecular weight of ca. 375 g/mol) were incubated at room temperature for a period of 24 h with the synthetic peptides at ratios of 1:5 (for C-peptide) or 1:24 (for K-peptide) concerning absolute mass. Triplicates of the concurrent vehicle control were incubated with the respective peptides under the same conditions. In addition, a test substance control, consisting of the test substance in vehicle and the respective peptide buffer without peptides, was analysed in parallel in order to detect possible interference of the test substance with the peptides during analysis (co-elution control). After incubation, the remaining non-depleted peptide concentration was determined by HPLC/DAD with gradient elution and UV-detection at 220 nm. The peptide depletion of samples incubated with the test substance was compared to the peptide depletion of the vehicle control samples and expressed as relative peptide depletion. The mean C- or K-containing peptide depletion caused by the test substance was determined to be 0.2 and -1.1% (set to zero), respectively. Thus, a mean peptide depletion of 0.1% was calculated. No co-elution of test substance and peptides was detected. The positive control p-benzoquinone produced a mean peptide depletion of 98 and 100% for the C- or K-containing peptide, respectively, and thus showed the expected results of high chemical reactivity (> 42.47% mean peptide depletion). Based on these results and according to the prediction model proposed by Gerberick et al. (2007), it was concluded that the test substance showed a minimal chemical reactivity (< 6.38% mean peptide depletion) in the DPRA under the test conditions chosen.

 

CAS 63705-03-3

Two studies investigating the skin sensitising potential of and 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3) are available.

A study was performed according to a Buehler test protocol similar to OECD Guideline 406 in Pirbright white guinea pigs and under GLP conditions (Kaestner, 1989). The test material was diluted in paraffin perliquid DAB 8 (1st Induction and challenge) or vaseline (2nd and 3rd induction) and applied at a concentration of 50% for epidermal induction and challenge and at concentration of 25% for rechallenge. The negative control group was treated with the vehicle only. No positive control data was included in the study report for reliability check.

The test animals were treated with the product on the right body side three times in intervals time of one week each. The substance was applied at a concentration of 50% under occlusive conditions for 6 hours every time on the same skin areas. The control group was treated with vehicle only.

14 days later the test and control animals were treated on the right and left body side with the test substance at a concentration of 50% with patches for 6 h (challenge).

One week later the rechallenge treatment was conducted on test and control animals and the test substance was applied the left body side with a 25% solution. After challenge and rechallenge at patch removal, very slight skin reactions were seen at the first reading (24 h after challenge) in test and control animals and were reversible in all animals within 48 h. These reactions were probably caused by an irritating effect of the test substance. These reactions were nearly the same on both groups. At the second reading after challenge (48 h) and rechallenge no effects in terms of skin reactions were observed in both groups.

According to these results the test substance can be classified as not sensitizing.

A not sufficiently documented (no data on positive control substance or historical controls and lack of data on test substance) guinea pig maximisation test was performed to assess the skin sensitisation potential of 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS# 63705-03-3), (Kästner, 1988). 20 female Pirbright-Hartley guinea pigs were treated with the test substance at 0.1% for intra- and 40 % for epidermal induction on Days 1 and 8, respectively. 19 animals served as negative controls. A positive control group was not included in the study and no information is given on periodical testing of strain sensitivity, either. 14 days after the epidermal induction, epidermal challenging was performed with a 10% and 15% test material dilution in Paraffinum perliquidum DAB 8.

24 and 48 h after challenging skin examination revealed irritation in the test group and in the control group. Rechallenge treatment (conducted on the left flank 7 days after challenge) with 8% test substance showed irritation in the test group and in the control group, while the rechallenge with 4% of the test substance did neither in the test substance group nor in the negative control group result in any erythema or edema at the 24 and 48 h reading time points.

With regard to the results of the challenge with 10 and 15% of the test substance, the conclusion could be drawn, that the test substance has a skin sensitizing potential. The results of the rechallenge with 4 and 8% of the test substance, however, might indicate that the skin reactions were caused by an irritative effect of the test substance.

Due to the fact that a high concentration of 40% for the epicutaneous induction was required to induce a slight to moderate irritation, it has to be concluded that the low concentrations of the rechallenge were not sufficient to penetrate the intact skin. Therefore, the results of the rechallenge are of minor importance.

Taken together, the results of this study report were judged as ambiguous.

 

Conclusion for skin sensitisation properties

Taken together, all available data for assessment of the skin sensitising potential indicate that Oleic acid, monoester with oxybis(propanediol) (CAS# 49553-76-6) has no skin sensitisation potential and classification according to EU classification criteria for skin sensitisation is not required.

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

Migrated from Short description of key information:
Skin sensitisation: not sensitising (DPRA, OECD 406, and QSAR, analogue approach)

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Migrated from Short description of key information:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.