Registration Dossier

Diss Factsheets

Administrative data

Description of key information

GPMT: not sensitising (read-across from CAS 105-99-7)

Buehler Test: sensitising (read-across from CAS 16958-92-2)

HRIPT: not sensitising (read-across from CAS 16958-92-2)

Key value for chemical safety assessment

Skin sensitisation

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

Justification for read-across

Data on the skin sensitising potential of bis(1-methylheptyl) adipate (CAS 108-63-4) are not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across and a weight of evidence approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/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 substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

CAS 105-99-7

The skin sensitising potential of dibutyl adipate (CAS 105-99-7) was studied in female guinea pigs according to the maximisation method described in OECD guideline 406 (Hüls AG, 1989c). In the induction phase, intradermal injections of the test substance at 20% in maize oil and/or FCA were applied into the clipped skin area of 20 animals. A control group, consisting of 10 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 7. 24 hours later, the epicutaneous induction treatment with the undiluted test substance (100%) or the vehicle alone was conducted in the treated or control animals on the regions of intradermal injections for a period of 48 h. On Day 22, the challenge treatment was performed by topical application of the undiluted test substance 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 with the undiluted test substance in any of the animals of the test and control groups. Therefore, the test substance had no sensitising effect on guinea pigs under the chosen experimental conditions.

CAS 16958-92-2

In a study similar to OECD guideline 406, the skin sensitisation potential of bis(tridecyl) adipate (CAS 16958-92-2) was investigated in female guinea pigs according to the non-adjuvant Buehler method (Mobil, 1986). Based on a primary irritation test, the induction treatment of the main assay was performed with the test substance at concentrations of 50% (w/w) in Squibb Mineral oil. In the induction phase, the diluted test substance was applied to the clipped skin of the flank of 10 animals using an occlusive dressing. During induction, three consecutive topical applications for a period of 6 h were performed at intervals of 7 days. A group of 10 animals served as controls. After a 19-day rest period, the challenge exposure was performed in control and treated animals. Since the test substance at 50% solution caused significant dermal responses, test substance at a concentration of 25% in Squibb Mineral oil was used for the challenge treatment. The test substance was applied to the clipped skin of the right flank of the animals for 6 h and skin reactions were evaluated 24 and 48 h after application. The test substance at 25% (w/w) solution caused positive skin reactions in 9/10 treated animals 24 and 48 h after challenge exposure. Since positive reactions were also observed in the control group, a rechallenge was performed one week later. The treated animals and additional 5 (naïve) control animals were rechallenged with test substance at concentrations of 12.5% and 20% in Squibb Mineral oil. At 24 and 48 h reading, positive skin reactions were seen in 3/10 and 2/10 animals rechallenged with the test substance at 12.5%, whereas 4/10 animals at 24 and 48 h after rechallenge positively responded to 20% of the test solution. No positive skin reactions were observed in any of the animals of the control group. During the study no test substance-related clinical signs and no effects on body weight gain were observed. The sensitivity of the assay was confirmed with the positive control 2,4-dinitrochlorobenzene (0.1% in 70% ethanol), which showed the expected results in the test animals (10/10 animals with positive results). Based on these results, the test substance was found to be a sensitiser in guinea pigs in the non-adjuvant Buehler test.

Thus, the skin sensitisation potential of bis(tridecyl) adipate was further investigated in a Human Repeated Insult Patch Test (HRIPT) in 104 volunteers (Exxon, 1987). The undiluted test substance (0.2 mL) was applied to the skin of the back of 19 male and 85 female subjects, either under occlusive (55 subjects) or under semi-occlusive (49 subjects) conditions. A series of 9 induction patches were applied for a period of 3 weeks on Mondays, Wednesdays and Fridays. The patches with the test substance were removed after 24 hours, and reactions were scored after a rest period of 24 or 48 hours. After the induction phase, a further rest period of two weeks followed. Then, the challenge patch was applied for 24 hours to a virgin site of the back and reactions were scored after 24, 48, and 72 hours. No skin sensitisation reactions were observed in the subjects, neither under occlusive nor under semi-occlusive conditions. Based on these results, the test substance was not found to be a human skin sensitizer.

Overall conclusion

Regarding the source substance bis(tridecyl) adipate (CAS 16958-92-2) the non-adjuvant Buehler test in female guinea pigs revealed a positive result, however there is strong evidence from the human sensitisation data that show that the test substance is not a sensitizer in humans. Moreover, the available GPMT with the source substance dibutyl adipate (CAS 105-99-7) also revealed a negative result. Therefore, for the target substance no sensitising potential is expected.

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 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” 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 analogue concept is applied to bis(1-methylheptyl) adipate (CAS 108-63-4), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

The available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.