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 Polyfunctional acid ester (PFAE) aromatic category covers fatty alcohol esters of Benzene-1,2,4-tricarboxylic acid. The category contains both mono constituent and UVCB substances with fatty alcohol carbon chain lengths from C8-C13 (linear and iso-alcohols) building tri-esters with Benzene-1,2,4-tricarboxylic acid in variable proportions. A further surrogate substance of similar structure is included, namely a triester of Benzene-1,2,4-tricarboxylic acid with a C8 alcohol, but the alcohol moiety is branched (2-ethylhexyl).

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 data for source substance(s) within the group by interpolation to the target substances in the group (read-across approach) applying the group concept in accordance with Annex XI, Item 1.5, of Regulation (EC) No 1907/2006. In particular, 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 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:

Table: Skin and Eye irritation

ID No.

CAS

Skin irritation/corrosion

Eye irritation

#1

3319-31-1 (c)

Not irritating

Not irritating

#2

90218-76-1 (b) (former CAS: 67989-23-5)

Not irritating

Not irritating

#3

36631-30-8

Not irritating

Not irritating

#4

94279-36-4 (a)

Not irritating

Not irritating

#5

72361-35-4

RA: CAS 90218-76-1
RA: CAS 3319-31-1

RA: CAS 36631-30-8

RA: CAS 94279-36-4

RA: CAS 90218-76-1
RA: CAS 3319-31-1

RA: CAS 36631-30-8

RA: CAS 94279-36-4

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

(b) Substances that are either already registered under REACh or not subject to the REACh Phase-in registration deadline of 31 May 2013 are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

(c) Surrogate substances are either chemicals forming part of a related category of structurally similar fatty acid esters or precursors/breakdown products of category members (i.e. alcohol and fatty acid moieties). Available data on these substances are used for assessment of toxicological properties by read-across on the same basis of structural similarity and/or mechanistic reasoning as described below for the present category.

 

Skin irritation

CAS 94279-36-4

The skin irritation potential of 1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters (CAS 94279-36-4) has been investigated in two studies in rabbits.

One study investigating the skin irritation potential of 1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters (84% pure) was performed in New Zealand White rabbits according to OECD guideline 404 under GLP conditions (Weterings and Daamen, 1987). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of the right flank of 3 female rabbits under semiocclusive conditions. The untreated site of the animals served as control. After patch removal residues of the test substance were washed off. The scoring of skin reactions (erythema and edema) was performed 55 min, 24, 48 and 72 h as well as 7 and 14 days after removal of the dressing. The skin of all three animals showed well-defined erythema (mean scores over 24, 48 and 72 h per animal: 1.67, 1.0, and 1.0, respectively) and very slight to slight edema (mean scores over 24, 48 and 72 h per animal: 1.0, 1.0, and 1.33, respectively). The redness had decreased to very slight within 24 h in 2 animals and on day 3 in one animal. All effects were fully reversible within 7 days in 2 animals and within 14 days in one animal.

An additional study was performed according to OECD 404 with 1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters (no data on purity) under GLP conditions (Dreher, 1991). 0.5 mL of the test substance was applied to the clipped skin of 3 male New Zealand White rabbits for 4 h. After removing the semiocclusive dressing the test site was gently washed. The skin reactions were scored after 1, 5, 24, 48, and 72 hours and 5, 7, 9, and 11 days after treatment. Very slight erythema (score = 1) was noted in one animal 1 h after and in all animals 5 and 24 h after patch removal. This effect lasted until the 48 h scoring in only one animal. No edema was observed in any animal. Thus, all effects were fully reversible within 72 h at the latest and the test substance was considered non-irritating.

In summary, 1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters is not irritating to the skin.

CAS 90218-76-1

The skin irritation potential of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters has been investigated in one study performed according to OECD 404 (no GLP) in rabbits (Mürmann, 1989). 3 Small White Russian rabbits were treated with 0.5 mL of the test substance (approx. 99% pure) at the shaved skin of the dorsal and lateral parts of the trunk under semiocclusive conditions. The untreated sites served as control. After 4 h treatment the test site was washed with water and scoring was performed 1, 24, 48, and 72 hours as well as 8 days after patch removal. All animals showed slight to well-defined erythema (mean scores over 24, 48, and 72 h per animal: 1.0, 2.0, and 1.67, respectively). Scurf formation in one animal was seen (time point not specified). Slight edema (grade = 1) was seen in one animal at the 1 h reading and in another animal at the 24 h reading (mean scores over 24, 48, and 72 h per animal: 0.0, 0.0, and 0.33, respectively). All effects were fully reversible within 8 days at the latest. Based on the evaluation scheme of the current guideline, the test substance is considered non-irritating as the scores were below the threshold for classification.

CAS 36631-30-8

The skin irritation potential of Triisodecyl benzene-1,2,4-tricarboxylate has been investigated in one study performed equivalent to OECD 404 (no data on GLP) in rabbits (Bouffechoux, 1996). The undiluted test substance (no data on purity) was applied to the clipped skin of 3 New Zealand White rabbits followed by a 7 day observation period. No information on substance volume, treatment period or conditions (occlusive or semiocclusive) is given in the report. However, the mean scores out of all 3 animals over 24, 48, and 72 h for erythema and edema are 0.0, respectively. Thus, no effects were seen at the scoring time points that are relevant for classification and the test substance was considered non-irritating to the skin.

CAS 3319-31-1

The skin irritation potential of Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate has been investigated in one study performed equivalent to OECD 404 (no data on GLP) in rabbits (Southwook, 1987).

0.5 mL of the test substance (no data on purity) was applied to the shaved skin of the dorso-lumbar region on the left flank of 3 females New Zealand White rabbits under semiocclusive conditions. After 4 h the dressing was removed and the test site was cleansed with water. Scoring was performed after 30-60 min, 24, 48, and 72 h as well as 8 days after patch removal. Very slight to well defined erythema (mean scores over 24, 48, and 72 h per animal: 0.7, 1.0, and 1.3, respectively), which were fully reversible within 8 days were seen in all animals. Edema was only seen in one animal that was fully reversible within 48 h (mean scores over 24, 48, and 72 h per animal: 0.0, 0.0, and 0.3). Based on the results of this study the test substance is considered non-irritating to the skin. 

 

Eye irritation:

CAS 94279-36-4

The eye irritation potential of 1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters was investigated in a study according to OECD guideline 405 under GLP conditions (Dreher, 1991). 0.1 mL of the undiluted test material (no data on purity) was placed into the conjunctival sac of the right eye of 3 male New Zealand White rabbits. The other eye remained untreated and served as control. The eyes were examined and scored 24, 48, and 72 h after application. No effects on iris, cornea or conjunctivae were observed in the animals at any reading time point. No further local or systemic toxic effects were observed. Therefore, the observation period was reduced to 72 h. The mean cornea, iris, conjunctivae and chemosis scores after 24, 48, and 72 h were 0.0 for all 3 animals, respectively. Based on the results of this study, 1,2,4-Benzenetricarboxylic acid, tri-C9-11-alkyl esters is not eye irritating.

CAS 90218-76-1

The eye irritation potential of 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters was investigated in a study according to OECD guideline 405 (no GLP) in rabbits (Mürmann, 1989). 0.1 mL of the undiluted test substance (approx. 99% pure) was instilled into one eye of 3 Small White Russian rabbits. The other eye of each animal served as control. 72 h after application the treated eyes were rinsed with saline. Scoring was performed 1, 24, 48, and 72 h as well as 8 days after treatment. 1 hour after application circumcorneal injections in all animals and mild discharge in one animal were seen. These effects were fully reversible within 24 h. The mean scores over 24, 48, and 72 h for cornea, iris, conjunctivae and chemosis were 0.0, respectively for all animals. Therefore, 1,2,4-Benzenetricarboxylic acid, mixed decyl and octyl triesters is not eye irritating.

CAS 36631-30-8

The eye irritation potential of Triisodecyl benzene-1,2,4-tricarboxylate was assessed in a study performed equivalent to OECD 405 (no data on GLP) in rabbits (Bouffechoux, 1996). An undefined volume of the test substance (no data on purity) was instilled in one eye of 3 New Zealand White rabbits, respectively, followed by a 7 day observation period. No details are available on the reading time points but only the mean scores over 24, 48, and 72 h per animal are given. No effects were seen on cornea and iris in any animal and only slight effects were noted on conjunctival redness that were fully reversible within 72 h in all animals (mean scores: 0.33, 0.33, and 0.66, respectively). No data on chemosis were given. Based on these results, the test substance is considered non-irritating to the eyes.

CAS 3319-31-1

The eye irritation potential of Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate was assessed in a study performed equivalent to OECD 405 (no data on GLP) in rabbits (Southwood, 1987). 3 female New Zealand White rabbits received a single instillation of 0.1 mL of the undiluted test substance (no data on purity) into the conjunctival sac of the left eye. The animals were observed for 72 hours and scoring was performed at 1-2, 24, 48, and 72 hours after treatment. Conjunctival effects (slight redness and moderate discharge) were observed 1-2 hours after instillation in all animals. The mean scores over 24, 48, and 72 hours, however, were 0.0 for all assessed parameters (cornea, iris, conjunctivae, and chemosis) in all animals. Thus, the test substance was not irritating to the eyes in this study.

Conclusion for irritation

In conclusion, the skin irritation properties of the PFAE aromatic category members have been investigated in five in vivo studies indicating no or very low skin irritating properties. Therefore, none of the category members of the PFAE aromatic group is skin irritating.

In conclusion, the eye irritation properties of the PFAE aromatic category members have been investigated in four in vivo studies indicating no eye irritation properties. Therefore, none of the category members of the PFAE aromatic group is eye irritating.

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 aromatic Category, data will be generated from representative reference substance(s) within the category 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.