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EC number: 943-330-9 | CAS number: -
Skin sensitisation (OECD 406, GPMT): not skin sensitising
Data read-across from the source substance bis(2-(2-butoxyethoxy)ethyl)adipate (CAS No. 141-17-3)
Respiratory sensitisation: no data available
For each induction the highest concentration to cause mild-to-moderate skin irritation, but well-tolerated systemically, was used.
Based on the results of this preliminary test, a concentration of 5% was chosen for the intradermal application of the main test and a concentration of 100% was selected for the dermal induction.
A concentration of 50% was found to be the highest dose which did not cause any signs of irritation after a topical treatment over a period of 24 hours and therefore was chosen for the challenge application in the main test.
All animals of both groups survived throughout the test period.
Signs of irritation during the induction:
Intradermal Induction I (24-hour reading):
- Injection site 1: erythema grade 1 in 5/5 negative control-, in 5/5 positive control- and 10/10 test animals, oedema grade 1 in 5/5 negative control-, in 5/5 positive control- and 10/10 test animals
- Injection site 2: erythema grade 1 in 1/5 positive control animals, oedema grade 1 in 1/5 positive control animals
- Injection site 3: erythema grade 1 in 1/5 negative control-, in 5/5 positive control- and 5/10 test animals, oedema grade 1 in 1/5 negative control-, in 5/5 positive control- and 5/10 test animals
Intradermal Induction I (48-hour reading):
- Injection site 2: no signs of irritation
- Injection site 3: erythema grade 1 in 1/5 negative control-, in 5/5 positive control and 5/10 test animals, oedema grade 1 in 1/5 positive control- and 1/10 test animals
Dermal Induction II (48-hour exposure, occlusive):
- Immediately after removing the patch: no signs of irritation in any of the test or control animals.
- 24 hours after removing the patch: no signs of irritation in any of the test or control animals.
Justification for grouping of substances and read-across
The read-across approach uses 'bis(2-(2-butoxyethoxy)ethyl)adipate' (CAS No. 141-17-3) as structurally similar source substance to transfer (read-across) data to the target substance 'reaction mass of bis[2-[2-(2-butoxyethoxy)ethoxy]ethyl]adipate and [2-[2-(2-butoxyethoxy)ethoxy]ethyl](3,6,9,12-tetraoxahexadecyl)adipate' (EC No. 943-330-9). The common feature of the source substance and the target substance is that they are diester derivatives of adipic acid, containing only even numbered and linear ethoxylated side chains. Both carboxylic functions of adipic acid are used to form esters with ethylene glycol monobutyl ethers of varying length. While the side chains of the target substance contain tri- and/or tetraethylene glycol monobutyl ether moieties, the side chains in the source substance are made up solely of diethylene glycol monobutyl ether. Thus, the ethylene glycol monobutyl ether substituents in the target substance contain 1 or 2 additional ethylene glycol monobutyl ether units. Although the constituents of the target substance are hence larger in size and have a higher molecular weight, it can be assumed that no significant steric hindrance is introduced when compared to the smaller side chains of the source substance. All parts of the ethylene glycol monobutyl ether side chains are freely rotatable due to the fact that neither a ring system nor π-bonds exert any constraints on rotatability. Therefore, it is feasible to assume an identical environmental and metabolic fate of both substances. In order to avoid the need to test every substance for every endpoint, the read-across from an analogue substance 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 using adequate and reliable data from the source substance in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006 (REACH). Structural similarity and similarities in properties and/or activities of the source and target substance are the basis of read-across.
No data regarding skin sensitisation obtained with the target substance are available and therefore read-across of adequate information from the source substance is used. The skin sensitising potential of bis(2-(2-butoxyethoxy)ethyl)adipate (CAS No. 141-17-3) was studied in female guinea pigs according to the maximisation method described in OECD TG 406 (BSL, 2013b). In the induction phase, intradermal injections of the test substance at 5% in physiological saline 0.9% NaCl and/or FCA were applied into the clipped skin area of 10 animals. A control group, consisting of 5 animals, was injected with vehicle only and/or FCA. Since a preliminary study showed that the undiluted test substance did not induce skin irritation, the test area of control and treated animals was pre-treated with 10% sodium lauryl sulphate in vaseline to induce local irritation on Day 6. One day later, the epicutaneous induction treatment with the undiluted test substance (100%) was conducted in the test animals on the regions of intradermal injections for a period of 48 h. Control animals were tested with Vaseline only. On Day 22, the challenge treatment was performed by topical application of 50% test substance in vaseline to the skin of all animals for 24 h. No changes in body weight gain were observed between treated and control animals. No cutaneous reactions were provoked 24 and 48 h after challenge treatment in any of the animals of the test and control groups. A positive control group treated with a formulation of 25% 2-mercaptobenzothiazole in a 1:1 (v/v) mixture of FCA/physiological saline 0.9% NaCl was included in the study to prove the sensitivity of the test strain. Therefore, the test substance had no sensitising effect on guinea pigs under the chosen experimental conditions.
Conclusion on skin sensitisation
A reliable and adequate study performed with the source substance investigating the skin sensitisation potential yielded no skin sensitisation in guinea pigs. Thus, no hazard for skin sensitisation is identified for the target substance either.
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 physico-chemical, 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". Thus, data gaps can be filled by a read-across approach from a structural analogue source substance to avoid unnecessary animal testing.
The analogue concept is also used to derive the C&L of the target substance taking the properties of the source substance into account. Based on the analogue concept, 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.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
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