Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin irritation: not irritating, (OECD 404, analogue approach)
Eye irritation: not irritating, (OECD 405, analogue approach)

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

There are no data available for the irritation/corrosion of 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2). In order to fulfil the standard information requirements set out in Annex VIII, 8.1 and VIII, 8.2 in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted. In accordance with Article 13 (1) of Regulation (EC) No 1907/2006 “information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set put in Annex XI are met”. In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance listed below are selected as reference substances for hazard assessment.

Overview irritation/corrosion

CAS

Skin irritation

Eye irritation

25811-35-2

Target substance

RA: CAS 67762-53-2

RA: CAS 189200-42-8

RA: CAS 68424-31-7

RA: CAS 67762-53-2

RA: CAS 189200-42-8

RA: CAS 68424-31-7

 

67762-53-2

Not irritating

Not irritating

189200-42-8

Not irritating

Not irritating

68424-31-7

Not irritating

Not irritating

The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Skin irritation

CAS 67762-53-2

A primary dermal irritation study was performed comparable to OECD Guideline 404 with Fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) (Zolyniene, 1999). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. All three animals showed a very slight or slight erythema 1 hour after the test item application. Within 48 hours after removal of the patches the dermal effect was completely reversible. All treated skin sites appeared normal at the 72 hour observation. The mean erythema scores over 24, 48 and 72 hours were 0 for animal #1 and #2 and 0.33 for animal #3. No edema occurred in any of the tested animals at any reading time point. The test material is not considered irritating to the skin in this study.

CAS 189200-42-8

A primary dermal irritation study was performed with Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS 189200-42-8) comparable to OECD Guideline 404 and GLP (Frank, 1995). The shaved skin of six male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. No erythema and no edema occurred in any of the tested animals at any reading time point. At the 72 hour time point two animals showed desquamation. The test material is not considered irritating to the skin in this study.

CAS 68424-31-7

Three primary skin irritation studies were conducted to assess the skin irritation potential of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424 -31 -7). In the first primary skin irritation study, which was performed according to OECD Guideline 404 (Robinson, 1991a), the shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semiocclusive conditions. Skin reactions were assessed 1, 24, 48, 72 and 96 hours after removal of the test substance. The exposure period of 4 hours caused slight edema (grade = 1) in all animals 24 hours after removal of the test substance. The effect fully reversed within 48 hours. Erythema was seen at the test site of one animal (grade 2) and slightly at the test site of the other two animals (grade =1). Erythema reactions were completely reversed within 96 hours after removal of the test substance in all three animals. The mean erythema score over 24, 48 and 72 hours was 1.3 for animal #1 and #3 and 1.7 for animal #2. The mean edema score over 24, 48 and 72 hours was 0.3 for all three animals. All treated skin sites appeared normal at the 96 hour observation.

Two further studies, which were performed comparable to OECD Guideline 404, investigated primary dermal irritation of 0.5 mL test substance on the shaved skin of three male New Zealand White rabbits each for a single 4-hour application period (Robinson, 1991b + c). Skin reactions were assessed 1, 24, 48, 72, 96 hours and 7, 8 and 12 days after removal of the test substance. In the first study, moderate to severe erythema (maximum score = 4) and moderate to severe edema (maximum score = 4) were observed for 2 or 3 days after application in all animals. This regressed and no signs of erythema or edema were evident 4 to 12 days after application. Thickening of the skin at the application site was seen on one animal between 4 and 7 days after application. No other signs of irritations were observed. In the second study, very slight to well-defined erythema and very slight to slight oedema were observed in all animals The mean erythema score over 24, 48 and 72 hours was 1 for the first animal and 1.3 for the remaining two animals. The edema score over 24, 48 and 72 hours was 1 for the first animal and 1.7 for the remaining two animals. These reversed and no signs of erythema or oedema were evident 11 or 12 days after application. Slight desquamation at the application site of one animal was observed 7 days after application.

The test material is not considered irritating to the skin in with regard to the studies performed with Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids.

Eye Irritation

CAS 67762-53-2

Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Zolyniene, 1997). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 3 (1 male, 2 female) New Zealand White rabbits each. 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. One animal exhibited moderate conjunctival redness and two animals showed mild conjuctival redness. All three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 hour post treatment, one animal was free of conjuctival redness. All three animals were free of ocular irritation within 72 hours of treatment. The mean conjunctivae score out of all three animals over 24, 48 and 72 hours was 0.67. Thus, the test material is not considered irritating to the eyes in this study.

CAS 189200-42-8

Fatty acids C8-10, mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tridipentaerythritol (CAS 189200-42-8) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 under GLP conditions (Frank, 1995). The undiluted test material (0.1 mL) was applied into the conjunctival sac of 6 (5 male and 1 female) New Zealand White rabbits each. The animals were observed for 7 days and reactions were assessed 1, 24, 48, 72 hours and 7 days after instillation according to the Draize scoring system. One hour after instillation of the test substance, slight conjunctival redness and chemosis were observed in all animals. Chemosis was reversible within 24 hours whereas conjunctival redness was reversible in all animals within 7 days. The mean conjuctivae score out all six animals over 24, 48 and 72 hours was 0.44. Fluorescein staining of the cornea was observed in three animals at the 48 h reading time point. At the 72 h reading, no staining of the cornea was observed indicating that the corneal response was superficial and transient. Thus, the test material is not considered irritating to the eyes under the conditions of this study. 

CAS 68424-31-7

Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids

(CAS 68424-31-7) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 (Robinson, 1991d). The undiluted test material (0.1 mL) was applied into the conjunctival sac of three female New Zealand White rabbits each. The animals were observed for three days and reactions were assessed 1, 24, 48 and 72 hours after instillation according to the Draize scoring system. No corneal or iridial effects were observed. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approximately 1 hour after dosing. Thus, the test material is not considered irritating to the eyes in this study.

Conclusion for skin and eye irritation

Based on the results of the available studies, none of structurally related substances is considered skin irritating. Therefore, on the basis of these findings, no classification for skin irritation for all substances for 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2) is required.

Several acute eye irritation studies have been performed in rabbits in vivo. None of the structurally related substances showed an eye irritation potential. Therefore, no classification for eye irritation for all substances for 2,2-bis[[(1-oxoheptyl)oxy]methyl]propane-1,3-diyl bisheptanoate (CAS 25811-35-2) is required.


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 source and target substances 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 source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

The available data skin/eye irritation potential of structural related substances 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.

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