Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

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

Justification for grouping of substances and read-across

The category covers fatty acid polyesters of polyols (Trimethylolpropane (TMP) or Pentaerythritol (PE)) mixed with adipic acid. The category contains UVCB substances with fatty acid carbon chain lengths from C8-C18 (even-numbered, including linear saturated and unsaturated chains) building mono-, di-,tri- or higher esters with TMP or PE respectively in variable proportions.

The available data allows for an accurate hazard and risk assessment of the category and the category concept is applied for the assessment of environmental fate, environmental and human health hazards. Thus where applicable, environmental and human health effects are predicted from adequate and reliable read across data within the group applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006.

A detailed justification for the grouping of chemicals and read-across is provided in the technical dossier

(see IUCLID Sections 7.1 and 13) and within Chapter 5.1 of the CSR.

Endpoint specific data matrix:

ID #

Identifier

Skin Sensitisation

1

CAS 95912-89-3 (a)

Experimental result:
not sensitising

2

CAS 91001-61-5

RA:CAS 95912-89-3
RA:EC 921-836-0

3

EC 921-836-0

Experimental result:
not sensitising

(a) Category members subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in bold font.

Only for these substances a full set of experimental results and/or read-across is given.

Discussion

Skin sensitisation

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 (Haferkorn, 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 similar constituted groups were exposed 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. In addition, 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 reveal 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 intolerance 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 reveal any sensitising properties in the local lymph node assay.

Based on the available data, Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane is not sensitising.

 

EC (EINECS) 921-836-0

The skin sensitising potential of Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol (EC 921-836-0) was investigated in a Local Lymph Node Assay (LLNA) in female CBA/CaOlaHsd mice according to OECD guideline 429 and in compliance with GLP (Lütkenhaus, 2012). In a preliminary study, two animals were topically treated with the undiluted test substance to determine appropriate treatment concentrations for the main study. One animal was treated with acetone/olive oil (4:1 v/v) and served as vehicle control. Neither signs of systemic toxicity nor signs of irritation at the application site could be detected in any treated animal after an observation period of 48 h or 6 days. Based on these results, the neat test substance and concentrations of 50 and 25% in acetone/olive oil (4:1 v/v) were selected for treatment of 5 females per dose in the main experiment. A further group of 5 animals was treated with the vehicle alone. The test substance formulations or the vehicle were applied topically to the entire dorsal surface of each ear (25 µL/ear) for three consecutive days. Five days after the first topical application, draining auricular lymph nodes were excised and the cell proliferation of pooled lymph nodes from individual animals was measured by incorporation of ³H-methyl thymidine and expressed as the amount of radioactive disintegration per minute (DPM). The mean DPM/node for each test group was 2948.2, 3243.6 and 4198.2 at concentrations of 25, 50 and 100% of the test substance, respectively, compared to a mean control DPM/node value of 1897.6. Based on these results, stimulation indices of 1.6, 1.7 and 2.2 were calculated for the treatment concentrations of 25, 50 and 100%, respectively. The EC3 value could not be calculated as the stimulation indices of all concentrations were below 3. No local or systemic toxicity and no effects on body weights were observed. The historical positive control p-phenylenediamine at concentrations of 1% confirmed the sensitivity and reliability of the experimental technique. Under the above mentioned conditions, the test substance was not found to be a sensitiser in the LLNA.

Based on the available data, Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol is not sensitising.

 

Conclusion for sensitisation

In summary, skin sensitisation studies were performed in two PFAE mixed and branched category members in vivo, showing no potential for skin sensitisation.

In conclusion, the available data indicate that no hazard for skin sensitisation for any category members has to be expected.

 

A detailed reference list is provided in the technical dossier (see IUCLID, section 13) and within CSR. 


Migrated from Short description of key information:
The overall assessment of the available information gave no indication for sensitising properties of the category members.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

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 group concept is applied to the members of the PFAE mixed and branched category, data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the group concept, all available data on sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.