Registration Dossier

Administrative data

Description of key information

All available studies on skin and eye irritation showed no irritating potential of the category members.

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 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 irritation/corrosion

Eye irritation

1

CAS 95912-89-3 (a)

Experimental result:
not irritating

Experimental result:
non-corrosive

2

CAS 91001-61-5

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

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

3

EC 921-836-0

Experimental result:
not irritating

Experimental result:
not irritating

(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.

Irritation/corrosion

Discussion

Skin irritation

CAS 95912-89-3

A GLP-conform in vitro skin irritation study according to OECD guideline 439 was performed with Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) (Andres, 2012). In this study, a reconstructed three-dimensional human epidermis model was used to investigate the effects of the undiluted test substance on the viability of epidermal keratinocytes. After 60-min exposure the test substance, the viability of human keratinocytes was 99.4% compared to the negative control PBS (100%). The positive control 5% SDS significantly reduced the viability of cells compared to the negative control, thus fulfilling the criteria for the acceptability of the assay (relative viability ≤ 20%). Since the mean relative tissue viability was ≥ 50% after 60 minutes treatment, the test substance was considered to be non-irritant to human skin according to the criteria laid down in OECD guideline 439.

Based on the results of this study, Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane is not irritating to the skin.

EC (EINECS) 921-836-0

The skin irritation potential of Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol (EC 921-836-0) has been investigated in two studies in vitro.

To assess the corrosive potential of Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol, an in vitro skin corrosion test using a human skin model was performed according to OECD guidelines 431 and under conditions of GLP (Giarei, 2012). Two replicates of intact SkinEthic RHE tissue, a three-dimensional system of reconstructed epidermis of normal human keratinocytes with a functional stratum corneum, were topically treated with 40 µL of the undiluted test substance to assess the skin corrosion potential. Cells exposed to the same volume of water served as controls. After a treatment period of 3 min or 1 h at 37 °C, the mean cell viability compared to the control was determined to be 88.9 or 88.5 %, respectively. Glacial acetic acid was used as positive control substance and fulfilled the acceptance criteria (mean cell viability ≤ 40%). Based on the results of this study, the test material was considered to be non-corrosive to reconstructed human epidermis in vitro.

In a further study, an in vitro skin irritation test with the test substance was performed according to the reconstructed human epidermis (RHE) test method described in OECD guideline 439 (Giarei, 2012). Nine replicates of intact SkinEthic RHE tissue were exposed to the test substance for 42 min at room temperature, washed with PBS and incubated for further 42 h. Cells treated with PBS served as controls. After exposure to the test substance, the mean cell viability compared to controls was 85.4%. The positive control (5% of sodium dodecyl sulphate in PBS) showed the expected decrease in mean cell viability (≤ 40%). Under the conditions of this in vitro study, the test material was non-irritating to reconstructed human epidermis in vitro.

In summary, Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol is not irritating to the skin.

Eye irritation

CAS 95912-89-3

A Bovine Corneal Opacity and Permeability (BCOP) test was performed according to OECD guideline 437 to assess the potential ocular corrosivity and severe eye irritation potential of Fatty acids, C8-10, mixed esters with adipic acid and trimethylolpropane (CAS 95912-89-3) (Andres, 2012). In this GLP-conform study, the test substance at 10% solution in olive oil was applied to the epithelial surface of the isolated cornea of cattle for 10 min, followed by a 2-h post-exposure incubation period. After exposure, no changes in opacity and permeability were observed in corneas compared to control. Based on the measurements for opacity and permeability, an In Vitro Irritancy Score (IVIS) ≤ 55 was calculated after treatment with the test substance (IVIS of the test substance= 0.217). The positive and negative controls showed the expected results, thereby confirming the validity of the assay. Based on the results of the study, no risk for serious damage to the eyes was identified. However, negative in-vitro corrosivity responses are not conclusive with respect to non-classification or classification as irritant and shall therefore be subject to further evaluation.

 

EC (EINECS) 921-836-0

An eye irritation study was performed with Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol (EC 921-836-0) according to OECD guideline 405 and under conditions of GLP (Freli, 2012). The undiluted test material (0.1 mL) was placed into the conjunctival sac of one eye of 3 male New Zealand White rabbits. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after application. At the 1 h reading, conjunctival redness (grade 1) was observed in all animals, but was fully reversible at 24 h reading. No effects on cornea, iris or conjunctivae swelling (chemosis) were observed in any animal during the study period. No further local or systemic toxic effects were observed. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0 for all 3 animals, respectively.

Based on the results of this study, Mixed esters of fatty acid C16 and C16-18-unsatd., with adipic acid and pentaerythritol is not eye irritating.

Conclusion for irritation

In conclusion, the skin irritation properties of two PFAE mixed and branched category members have been investigated in vitro, indicating no skin irritating properties. Therefore, none of the category members of the PFAE mixed and branched TMP/PE group is considered skin irritating.

In conclusion, the eye irritation properties of the two PFAE mixed and branched category members have been investigated in vitro and/or in vivo indicating no eye irritation properties. Therefore, none of the category members of the PFAE linear group is considered eye irritating.

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

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 skin irritation/corrosion and eye irritation 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.