Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In vivo skin irritation: not irritating (read-across from CAS 16958-92-2)

In vivo eye irritation: not irritating (read-across from CAS 105-99-7)

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for read-across

Adequate data on the skin and eye irritation potential of bis(1-methylheptyl) adipate (CAS 108-63-4) were not available. The assessment was therefore based on studies conducted with analogue substances as part of a read across 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).

Skin

CAS 16958-92-2

In a GLP-conform study, bis(tridecyl) adipate was tested for its skin irritation potential in New Zealand White (Hsdlf:NZW) rabbits according to OECD guideline 404 (Harlan, 2012). The test substance was applied to the clipped skin of the back of 1 male and 1 female rabbit using a semi-occlusive dressing. After an exposure period of 4 h, the test substance was removed and scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. Very slight erythema (grade 1) was noted in 1 animal at the 24 h reading, which was fully reversible 48 h after treatment. No further skin reactions (erythema and edema) were observed in both animals. The mean erythema and edema scores after 24, 48 and 72 h were 0.33 and 0 in one animal. In the other animal, the mean erythema and edema scores after 24, 48 and 72 h were 0, respectively.

CAS 105-99-7

The skin irritation potential of dibutyl adipate was investigated in a study according to OECD guideline 404 (Hüls AG, 1989a). The undiluted test substance (0.5 mL) was applied for 4 h to the clipped skin of 3 male Small White Russian, Chbb‐SPF rabbits under semi-occlusive conditions. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h as well as 6 and 8 days after removal of the dressing. At the 1 h reading time point, all 3 animals exhibited slight to obvious erythema (grade 2) and very slight edema. At the 24 and 48 h reading, 2/3 animals showed well-defined erythema, which in one animal increased to moderate erythema at the 72 h reading. Only slight erythema was observed after 24, 48 and 72 h reading in the third animal. Erythema was fully reversible after a period of 6 days in each of the animals. The formation of very slight to slight edema was observed in 2/3 animals at 24, 48 and 72 h reading, but was fully reversible within 6 days. In one rabbit, scaling was evident at the treatment side after 6 days, whereas another rabbit exhibited eschar formation at this time point. However, both effects were fully reversible within the 8-day observation period. No signs of systemic toxicity were seen. The mean erythema and edema scores after 24, 48 and 72 h were 2/1/2.33 and 1/0/1.33 for the 3 animals, respectively.

Eye

CAS 105-99-7

An eye irritation study was performed with dibutyl adipate according to OECD guideline 405 (Hüls AG, 1989b). The undiluted test substance (0.1 mL) was placed into one eye of 3 Small White Russian, Chbb‐SPF rabbits. The other eye remained untreated and served as control. After 72-h exposure, treated eyes were washed with warm physiological saline. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48, 72 h and 6 days after test substance application. At the 1 h reading, obvious conjunctival redness (grade 1) was observed in 2/3 animals which completely disappeared within 24 hours. No irritation reactions on the cornea or iris were noted in the animals at any reading time point. No further local or systemic toxic effects were reported. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively.

Overall conclusion for skin and eye irritation

Based on the available data with the source substances, no skin or eye irritation potential is expected for the target substance bis(1-methylheptyl) adipate (CAS 108-63-4).

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 and eye irritation do not meet the classification criteria according to Regulation (EC) No. 1272/2008 and are therefore conclusive but not sufficient for classification.