Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin, rabbit (WoE): not irritating
Eye, rabbit (WoE): not irritating

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 analogue read-across

Data on the skin and eye irritation/ corrosion of Tetraesters of pentaerythritol with 2-ethylhexanoic acid, heptanoic acid and nonanoic acid (EC 806-879-4) are not available. The assessment was therefore based on studies conducted with analogue (source) 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 irritation

CAS 67762-53-2

A dermal irritation study was performed according to OECD guideline 404 with Fatty acids, C5-9 tetraesters with pentaerythritol (Zolyniene, 1999). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL undiluted test material for 4 hours under semiocclusive conditions. The skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. All three animals showed very slight to well defined erythema (score 1-2) 1 hour after patch removal, while only 1/3 animals had very slight erythema 24 hours after patch removal. The skin effect was completely reversible within the 48-hour reading time point. The mean erythema scores over 24, 48 and 72 hours were 0, 0 and 0.33. No edema was noted in any of the tested animals at any reading time point, leading to mean scores over 24, 48 and 72 hours of 0, 0 and 0. The test material is not considered irritating to the skin in this study.

CAS 78-16-0

A dermal irritation study was performed according to EU Method B.4 and under GLP conditions with 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane -1,3-diyl bisheptanoate (Weterings, 1987). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL undiluted test material for 4 hours under semiocclusive conditions. The skin reactions were assessed 50 min, and 24, 48 and 72 hours after removal of the test substance. All three animals showed very slight erythema (score 1) 1 hour and 24 hours after patch removal, while only 1/3 animals had very slight erythema 48 hours after patch removal. Very slight edema (score 1) was observe in 3/3 animals at the 24-hour reading time point only. All skin effects were completely reversible within 72 hours. The mean erythema scores over 24, 48 and 72 hours were 0.66, 0.33 and 0.33. The mean edema scores over 24, 48 and 72 hours were 0.33, 0.33 and 0.33. The test material is considered to be not irritating to the skin in this study.

CAS 68424-31-7

A primary dermal irritation study was performed according to OECD guideline 404 with Fatty acids, C5-10, esters with pentaerythritol (Robinson, 1991). The shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL undiluted test material for 4 hours under semiocclusive conditions. The skin reactions were assessed 30 - 60 min, and, 24, 48 72 and 96 hours after patch removal. All three animals showed well defined erythema (score 2) 24 hours after patch removal, while the severity gradually decreased to very slight erythema in 3/3 rabbits at the 72-hour reading time point. 3/3 animals had very slight edema (score 1) 24 hours after patch removal, which had cleared com completely within the 48-hour reading time point. All skin effects were reversible within 96 hours after patch removal. The mean erythema scores over 24, 48 and 72 hours were 1.33, 1.67 and 1.33. The mean edema scores over 24, 48 and 72 hours were 0.33, 0.33 and 0.33. The test material is considered to be not irritating to the skin under the conditions of this study.

CAS 7299-99-2

The dermal irritation potential of Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester was assessed in a study performed according to OECD guideline 404 and under GLP conditions (Bouffechoux, 1998). The shaved and abraded skin of three male New Zealand White rabbits was exposed to 0.5 mL undiluted test material for 4 hours under semiocclusive conditions. The skin reactions were assessed 4, 24, 48 and 72 hours, and 4 and 7 days after patch removal. 1/3 animals showed very slight edema (score 1) 4 hours after patch removal, while 1/3 animals (a different animal) had very slight edema 24 hours after patch removal. All skin effects were completely reversible within the 48-hour reading time point. The mean edema scores over 24, 48 and 72 hours were 0, 0.33 and 0. No erythema was noted in any of the tested animals at any reading time point, leading to mean scores over 24, 48 and 72 hours of 0, 0 and 0. The test material is not considered irritating to the skin in this study.

 

Eye irritation

CAS 67762-53-2

Fatty acids, C5-9, tetraesters with pentaerythritol was tested for its acute eye irritation potential in a study performed according to OECD guideline 405 (Zolyniene, 1997). 0.1 mL of the undiluted test substance was applied into one eye of each of 3 (1 male, 2 female) New Zealand White rabbits. The animals were observed for 3 days and reactions were assessed 1, 24, 48 and 72 hours after instillation according to the Draize scoring system. 3/3 animals showed slight to moderate conjunctival redness 2 hour after instillation. Slight conjunctival redness was noted in 2/3 rabbits until the 24-hour reading time point, which persisted in 1/3 until the 48-hour reading time point. All eye irritation effects had cleared completely within 72 hours after instillation. No chemosis and no iridial or corneal changes were observed in any rabbit at any time point. The mean conjunctivae score for the three animals over 24, 48 and 72 hours was 0.67, 0 and 0.33. In conclusion, the test substance was not considered irritating to the eye.

CAS 78-16-0

The eye irritation potential of 2-ethyl-2-[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate was assessed in a study performed according to EU Method B.4 and under GLP conditions (Weterings, 1987). 0.1 mL of the undiluted test substance was applied into one eye of each of 3 female New Zealand White rabbits. The treated eye was not rinsed. The other eye remained untreated and served as the control. Examination and scoring of effects on the eyes was performed at intervals of 1, 24, 48 and 72 h after test substance application. 3/3 animals showed slight to moderate conjunctival redness 1 hour after instillation. The conjunctival redness had cleared completely within 24 hours after instillation. No chemosis and no iridial or corneal changes were observed in any rabbit at any time point. The mean conjunctivae score for the three animals over 24, 48 and 72 hours was 0, 0 and 0. In conclusion, the test substance was not considered irritating to the eye.

CAS 68424-31-7

Fatty acids, C5-10, esters with pentaerythritol was tested for its acute eye irritation potential in a study performed similar to OECD guideline 405 (Robinson, 1991). 0.1 mL of the undiluted test substance was applied into the conjunctival sac of one eye each of 3 female New Zealand White rabbits. The animals were observed for three days and irritation reactions were assessed 1, 24, 48 and 72 hours after instillation according to the Draize scoring system. Slight conjunctival redness (score 1) was observed in 1/3 animals 1 hour after instillation. The effects had cleared completely within the 24-hour reading time point. The mean conjunctivae score for the three animals over 24, 48 and 72 hours was 0, 0 and 0. No chemosis and no iridial or corneal changes were observed in any rabbit at any time point. Therefore, the test substance was not considered irritating to the eyes under the conditions of this study.

CAS 7299-99-2

The eye irritation potential of Hexanoic acid, 2-ethyl-, 2,2-bis [ [(2-ethyl-1-oxohexyl)oxy] methyl] -1,3-propanediyl ester was assessed in a study performed according to OECD guideline 405 and under GLP conditions (Bouffechoux, 1998). The undiluted test substance (0.1 mL) was instilled into one eye of 3 male New Zealand White rabbits. The treated eye was not rinsed. The other eye remained untreated and served as the control. Examination and scoring of effects on the eyes was performed at intervals of 4, 24, 48 and 72 h, and 7 days after test substance instillation. Four hours after instillation of the test substance, 3/3 animals had moderate (score 2) conjunctival redness. At the 24 -hour reading time point, the irritation effect had reduced in severity to slight redness (score 1) in 3/3 rabbits, which cleared completely within 48 hours after instillation. No chemosis was observed, and no irritation effects were seen on the iris and cornea in any animal at any reading time point. No further local or systemic adverse effects were observed. In conclusion, the test substance was not considered irritating to the eye.

Overall conclusion for skin and eye irritation

The available data on suitable source substances did not show any skin or eye irritation effects. Therefore, the target substance Tetraesters of pentaerythritol with 2-ethylhexanoic acid, heptanoic acid and nonanoic acid is not expected to be a skin irritant or an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of eye irritation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

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 Tetraesters of pentaerythritol with 2-ethylhexanoic acid, heptanoic acid and nonanoic acid (EC 806-879-4), 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) 1272/2008, and are therefore conclusive but not sufficient for classification.