Fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol

Endpoint summary

Description of key information

Skin, rabbit: not irritating

Read-across from structural analogue source substances 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8, key)

Eye, rabbit: not irritating

Read-across from structural analogue source substances 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8, key)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Source: CAS 62125-22-8, 1984, RL2

Irritation parameter:

edema score

Basis:

mean

Remarks:

of all 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Source: CAS 62125-22-8, 1984, RL2

An in vivo skin irritation study in rabbits with the source substance 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) was selected as key result for reasons of structural similarity and data reliability. In a second study with this source substance absence of skin irritating potential was confirmed.

Supporting in vivo skin irritation data is given for the source substances fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2), fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8), and fatty acids, C5-10, esters with pentaerythritol (68424-31-7), where no or only mild oedema and erythema, not leading to classification, were found.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

In vivo skin irritation studies are available for the source substances CAS 62125-22-8, CAS 68424-31-7, CAS 67762-53-2 and CAS 189200-42-8, which revealed all non-irritating properties towards the skin. Applying the read-across approach, for the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol non-irritating properties towards the skin are expected.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

chemosis score

Basis:

animal: #1 and #3, respectively

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

chemosis score

Basis:

animal: #2, #4, #5 and #6, respectively

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #6, respectively

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #4, respectively

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

not fully reversible within: 48 and 72 h

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

other: reversibility was not assessed

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

other: reversibility was not assessed

Remarks on result:

other: Source: CAS 62125-22-8, 1982, RL2

An in vivo eye irritation study in rabbits with the analogue source substance 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) was selected as key result for reasons of structural similarity and data reliability. The observation period in the study was 72 hours, therefore reversibility of redness of conjunctivae was not determined in 2 out of 6 animals. In a second study with this source substance redness of conjunctivae was fully reversible within 48 hours. Supporting in vivo data on eye irritation is given for the source substances fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7), fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 67762-53-2), and fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8). No or only mild in vivo eye irritation potential was found in the studies.

Conclusions:

In vivo skin irritation studies are available for the source substances CAS 62125-22-8, CAS 68424-31-7, CAS 67762-53-2 and CAS 189200-42-8, which revealed all non-irritating properties towards the eyes. Applying the read-across approach, for the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol non-irritating properties towards the skin are expected.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

Adequate data on the skin and eye irritation potential of fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol was not available. The assessment was therefore based on studies conducted with analogue 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/corrosion

CAS 62125-22-8

Two primary skin irritation studies were conducted to assess the skin irritation potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8).

A primary dermal irritation study was performed with 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) according to OECD 404 and GLP (Notox, 1984). 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. The rabbits were observed for three days following exposure. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. Very slight erythema and very slight edema was observed 1 h after treatment, each in one animal. Effects were fully reversed within 24 h after treatment. The third animal was free of any skin irritation effect. Thus, the test material was not considered irritating to the skin in this study.

In a second primary dermal irritation study performed according to OECD 404 the skin of three male New Zealand rabbits was exposed to the test material for 4 hours (Cosmepar, 1997). Skin reactions were assessed 1, 24, 48 and 72 hours as well as 7 days after removal of the test substance. The exposure period of 4 hours caused only slight erythema (score 1) in two animals which was completely reversed within 48 and 72 hours, respectively. The mean score erythema score over 24, 48 and 72 h were 1.3, 0, and 0.3 for animal #1, #2, and #3 respectively. The third animal was free of any skin irritation. All treated skin sites appeared normal at the 72 hour observation. Thus, the test material was not considered irritating to the skin in this study.

CAS 68424-31-7

In a primary skin irritation study, which was performed according to OECD 404, 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 (ICI Central Toxicology Laboratories, 1991). 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 (score 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 (score 2) and slightly at the test site of the other two animals (score 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. The test material is not considered irritating to the skin in this study.

CAS 67762-53-2

A primary dermal irritation study was performed comparable to OECD 404 with fatty acids, C5-9 tetraesters with pentaerythritol (CAS 67762-53-2) (Huntington Life Sciences, 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 was 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 404 and GLP (ExxonMobil, 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 was not considered irritating to the skin in this study.

Eye irritation

CAS 62125-22-8

Two eye irritation studies were conducted to assess the eye irritation potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8).

In a first in vivo study performed comparable to OECD 405 the undiluted test material (0.1 mL) was applied into the conjunctival sac of six female New Zealand White rabbits each (Toxicol Laboratories, 1982). The animals were observed for 72 hours and reactions were assessed 1, 24, 48, and 72 hours after instillation according to the Draize scoring system. 24 h after exposure, chemosis was observed in 4 of 6 animals, which disappeared the next day. All 6 animals showed redness of the conjunctivae, which disappeared in three animals the next day. At 72 h observation, redness was still observed in two animals. Since the observation was stopped after 72 h, there is no information on the reversibility of these effects in the remaining two animals. The mean conjuctivae and chemosis score out of all six animals over 24, 48 and 72 hours were 0.78 and 0.22 respectively. Adverse effects on the cornea and the iris were not observed in any of the animals. Thus, the test material was not considered irritating to the eyes in this study.

In a second in vivo study performed comparable to OECD 405, the test material was applied into the conjunctival sac of three male New Zealand rabbits each (Cosmepar, 1997). The animals were observed for 72 hours and reactions were assessed 1, 24, 48, 72 hours and 7 days after instillation according to the Draize scoring system. All animals showed slight effects on the conjunctiva 1 hour after removal of the test substance. This effect lessened but was still visible for 2 animals 24 hours later but fully reversible thereafter. The mean conjuctivae score over 2 animals was 0.11, and 0 for the remaining animal. Thus, the test material was not considered irritating to the eyes in this study.

CAS 68424-31-7

Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7) was tested for its acute eye irritation potential in a study performed comparable to OECD 405 (ICI, 1991). 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 was not considered irritating to the eyes in this study.

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 405 (Huntingston Life Sciences, 1999). 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 was 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 405 under GLP conditions (ExxonMobil, 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 was not considered irritating to the eyes under the conditions of this study.

 

Overall conclusion for skin and eye irritation

The available data for the source substances do not indicate a skin and eye irritation potential. Therefore, no skin or eye irritation potential is expected for the target substance fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol.

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 fatty acids C18-C22 (even numbered), tetraesters with pentaerythritol, 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.

Applying the read across approach, 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.