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Description of key information

Skin sensitisation (similar to OECD TG 406, GLP, GPMT): not sensitising

Read-across from a key study with analogue source substance Isooctadecanoic acid, ester with oxybis[propanediol] (CAS No. 73296-86-3); further supported by read-across from analogue source substances Hexanedioic acid, mixed esters with decanoic acid, 12-hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS No. 130905-60-1) and 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS No. 63705-03-3)

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
Please refer to the Analogue Approach Justification provided in Section 13.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
Induction: 0%; challenge:100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Source, CAS 73296-86-3, Lasem, 2002
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Induction and challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Source, CAS 73296-86-3, Lasem, 2002
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
Induction: 5% in corn oil; challenge: 0.05% in petroleum jelly
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
erythema formation
Remarks on result:
other: Source, CAS 73296-86-3, Lasem, 2002
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
Induction: 0%; challenge:100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Source, CAS 73296-86-3, Lasem, 2002
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
Induction and challenge: 100%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Source, CAS 73296-86-3, Lasem, 2002
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
Induction: 5% in corn oil; challenge: 0.05% in petroleum jelly
No. with + reactions:
4
Total no. in group:
5
Clinical observations:
erythema formation
Remarks on result:
other: Source, CAS 73296-86-3, Lasem, 2002

Additional studies and results supporting the key study:

CAS 63705-03-3, BASF, 1989: not sensitising (Buehler)

CAS 130905-60-1, Sasol, 1990e: not sensitising (GPMT)

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
In a guinea pig maximisation test, no skin sensitisation was observed following occlusive epicutaneous challenge after induction treatments (intracutaneous injection and occlusive epicutaneous exposure).
Executive summary:

The skin sensitisation potential of the target substance is estimated based on an adequate and reliable in vivo key study of a structural analogue source substance. In the guinea pig maximisation test, no skin sensitisation was observed following occlusive epicutaneous challenge after induction treatments (intracutaneous injection and occlusive epicutaneous exposure). The results of the key study are further supported by additional (supporting) studies with analogue source substances following the Buehler and guinea pig maximisation test design. Therefore, for the target substance no hazard regarding skin sensitisation is identified. As explained in the analogue justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the skin sensitisation potential.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

The read-across from structural analogue source substances approach comprises aliphatic esters of the poly-functional alcohols di- and triglycerol. The fatty acid rests of the esters exhibit carbon chain lengths in the range C5 - C20. They are either linear and saturated in nature but also unsaturated C16 and C18 and branched C6 and C18 moieties are present. Since the alcohols employed provide 4 - 5 reactive hydroxyl functions, the esterification degree found in source and target substances ranges from mono- to penta-esters.

The available data allows for an accurate hazard and risk assessment of the target substance and the read-across concept is applied for the assessment of environmental fate and environmental and human health hazards. Thus, where applicable, environmental and human health effects are predicted from adequate and reliable data for source substances by interpolation to the target substance applying the read-across concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH). In particular, for each specific endpoint the source substances structurally closest to the target substance 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 substances 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 section 13).

The skin sensitisation potential of the target substance has not been investigated. Therefore, data from a key study performed with the closes structural source substance is used to read-across information regarding this endpoint to the target substance. The findings of the key study are supported by additional studies with two other analogue source substances.

The key study investigated the skin sensitisation of the analogue substance Isooctadecanoic acid, ester with oxybis[propanediol] (CAS No. 73296-86-3). The Guinea Pig Maximisation Test (GPMT) was performed similar to OECD TG 406 and observed GLP provisions (Lasem, 2002). 3 male and 2 female Hartley guinea pigs were subject to both intradermal injections as well as epidermal exposure (48 h) with the undiluted test substance. The negative control consisted of 2 males and 3 females and a positive control group ( 1-Chloro-2,4-dinitrobenzene, 3 males, 2 females) was also included in the study. Challenge was performed by epidermal exposure to the undiluted test substances for 24 h. Skin reactions were recorded 24, 48 and 72 h after the challenge. No effects on the skin of the treated animals (0/5) were observed in the test and negative control groups, respectively. The positive control substance induced positive reactions in 4/5 animals, thus demonstrating the validity of the test. The test substance is therefore not considered to induce skin sensitisation.

A supporting Guinea Pig Maximisation Test (GPMT) to assess the skin sensitisatin potential was performed with Hexanedioic acid, mixed esters with decanoic acid, 12-hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS No. 130905-60-1) according to OECD TG 406 (Sasol, 1990e). 20 Pirbright white guinea pigs were treated with 5 and 25% test substance for intra- and epidermal induction (48 h), respectively. 20 further animals served as negative control. Epidermal challenge was performed with 25% of the test substance for 24 h. Skin examination revealed no positive skin reactions in any of the animals, neither in the negative control group nor in the test group. No positive control substance was tested. Based on the available data, the test substance is not regarded as a skin sensitiser.

 

In the second supportive study, skin sensitisation following the Buehler design was tested with 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS No. 63705-03-3) similar to OECD TG 406 (BASF, 1989). 20 Pirbright white guinea pigs were treated for 6 h with 50% test substance for epidermal induction (occlusive). 19 further animals served as negative control. Epidermal challenge was performed with 50% of the test substance for 6 h and rechallenge with 25% of the test substance. After the first reading (24 h), skin examination revealed 3/19 positive skin reactions in the negative control and 5/20 in the test group. After the second reading (48 h), skin examination revealed no positive skin reactions, neither in the negative control nor in the test group. After the rechallenge (24 h) skin examination revealed 10/19 positive skin reactions in the negative control and 5/20 in the test group. At the second timepoint of the rechallenge (48 h), skin examination revealed no positive skin reactions, neither in the negative control nor in the test group. As these reactions were only slight reactiions (score = 1) and were reversible in all animals within 48 h, they were most probably caused by an irritating rather than a sensitising effect. No data on any positive control substance was provided in the report. Based on the available data, the test substance is not regarded as a skin sensitiser.

Conclusion on skin sensitisation

Based on the results of the key and two supporting studies with adequate analogue source substances, no potential for skin sensitisation has been observed in any of the investigations. Therefore, the target substance Isooctadecanoic acid, mixed esters with oxybis[propanediol] is also considered not to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 (REACH) information on intrinsic properties of substances may be generated by means other than tests, e.g. using information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI 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 read-across concept is applied to the target substance Isooctadecanoic acid, mixed esters with oxybis[propanediol], data gaps can be filled by interpolation from representative structural analogue source substances to avoid unnecessary animal testing.

The read-across concept is also used to derive the classification of the target substance taking the properties of the source substances into account. Based on the read-across concept, all available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification.