Registration Dossier

Administrative data

Description of key information

Skin sensitisation (OECD 429, GLP, read across): not sensitising

Skin sensitisation (OECD 406, GLP, read across): not sensitising

Key value for chemical safety assessment

Skin sensitisation

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

Justification for read-across

There are no data available on skin sensitisation of the target substance Nonanoic acid, esters with adipic acid and trimethylolpropane. Therefore, read-across from the appropriate structural analogue substances trimethylolpropane tripelargonate (CAS 126-57-8) and Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) is conducted in accordance with Regulation (EC) No 1907/2006, Annex XI, 1.5. in order to fulfil the standard information requirements defined in Regulation (EC) No 1907/2006, Annex VII, 8.3. Common functional groups and structural similarities combined with similar toxicokinetic properties of the source and target substances 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 126-57-8

A Guinea Pig Maximisation Test was performed with trimethylolpropane tripelargonate (CAS 126-57-8) according to OECD guideline 406 and under GLP conditions (RTC, 2014). A range-finding study was performed to select the doses for the main study. In the main study, 10 female Dunkin-Hartley guinea pigs were treated with the test substance at 20% in corn oil for intra- and epidermal induction on days 1 and 8, respectively. 14 days after the epidermal induction, epidermal challenge was performed with the test substance at 20% in corn oil. No positive control substance was included in the study. No clinical signs were observed. 0/10 animals of the treatment group showed skin sensitising properties, when used at a dose level of 20% for induction and challenge. Due to the lack of a positive control group, the study cannot be used for classification.

CAS 95912-89-3

To assess the skin sensitisation potential of Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3), a modified LLNA in NMRI mice was performed according to OECD guideline 429 and under the conditions of GLP (LPT, 2012). Based on a preliminary experiment in 3 animals, the undiluted test substance (100%) and dilutions of the test substance in acetone/olive oil (3+1 v/v) at concentrations of 25 and 50% (w/w) were tested in six female mice per group. During 3 consecutive days, the dorsal surface of both ears of each animal was epidermally treated once daily with the undiluted test substance and their respective dilutions (25 μL/ear). Two groups were exposed according to the same protocol as the treatment animals to the vehicle and the positive control substance hexyl cinnamic aldehyde at a concentration of 25% in the vehicle, respectively. Before the first application of the test substance and at sacrifice (Day 4 of the study), skin irritation was assessed by measuring the ear thickness of the animals. On Day 4, punch biopsies of the apical area of both ears were prepared and weight for the determination of irritating effects. Furthermore, the draining (auricular) lymph node of each ear was excised and weighed for the assessment of skin sensitisation. Single cell suspensions of pooled lymph nodes from each individual animal per group were prepared and cell proliferation was measured by automatically counting the lymph node cells. Stimulation indices were calculated for the lymph node cell count, lymph node weight, ear weight and ear thickness by dividing the average values per group of the test item treated animals by the vehicle treated ones. Treatment with test substance at concentrations of 25%, 50% or 100% did not lead to statistically significantly increased values for lymph node cell count. The stimulation indices (SI) of the lymph node cell count of the test substance (1.029, 1.308 and 1.212 at 25, 50 and 100%, respectively) did not exceed the threshold level for a positive result (SI > 1.4). Since the threshold level for the SI of the ear weight was not exceeded (SI < 1.1) and no increase of ear thickness was observed, the test substance was not considered to show irritating properties. The positive control substance hexyl cinnamic aldehyde induced the expected increase in lymph node cell count (SI > 1.4) and lymph node weight (statistically significant at p ≤ 0.01), thereby verifying the validity of the study. No signs of local or systemic adverse effects were recorded and the body weight of the animals was not affected by treatment. Under the present test conditions, the test substance at concentrations of 25% and 50% (w/w) in acetone/olive oil (3+1 v/v) and the undiluted test substance (100%) did not induce any skin sensitising properties in the local lymph node assay.

 

Overall conclusion

The available data with the analogue substances trimethylolpropane tripelargonate (CAS 126-57-8) and Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) revealed no sensitising properties to the skin, respectively. Therefore applying the read-across approach similar results are expected for the target substance.

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 Nonanoic acid, esters with adipic acid and trimethylolpropane, 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.

Therefore, based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.