Pentaerythritol tetrastearate

Endpoint summary

Description of key information

Skin, rabbit (Read-across, according to OECD 404): not irritating

Eye, rabbit (Read-across, similar to OECD 405): not irritating

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:

Please refer to the Analogue Approach Justification provided in 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:

animal: #1, #2, #3

Remarks:

individual mean over

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)

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Remarks:

individual mean over

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversiblity not applicable

Remarks on result:

other: Source: CAS 62125-22-8 (1984)

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 eye 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) 1272/2008.

Executive summary:

The read-across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their skin irritation potential. No in vivo skin irritation potential was found in rabbit studies for the four source substances with structural similarity. Therefore, no skin irritation potential is expected for target substance Pentaerythritol tetrastearate (CAS 115-83-3).

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:

Please refer to the Analogue Approach Justification provided in 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:

animal: #1, #2, #3, #4, #5, #6

Remarks:

individual mean over

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

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3, #4, #5, #6

Remarks:

individual mean over

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Remarks on result:

other: Source: CAS 62125-22-8

Irritation parameter:

chemosis score

Basis:

animal: #1 and #3

Remarks:

individual mean over

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

Irritation parameter:

chemosis score

Basis:

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

Remarks:

individual mean over

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

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #6

Remarks:

individual mean over

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

Irritation parameter:

conjunctivae score

Basis:

animal: #1 and #4

Remarks:

individual mean over

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 48 h and 72 h

Remarks on result:

other: Source: CAS 62125-22-8

Irritation parameter:

conjunctivae score

Basis:

animal #5

Remarks:

individual mean over

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

Irritation parameter:

conjunctivae score

Basis:

animal #3

Remarks:

individual mean over

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

other: reversiblity was not assessed

Remarks on result:

other: Source: CAS 62125-22-8

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. No eye irritation potential is expected for target substance Pentaerythritol tetrastearate (CAS 115-83-3).

Interpretation of results:

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

Executive summary:

The Read-across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their eye irritation potential. No in vivo eye irritation potential was found in rabbit studies with four source substances. Therefore, no eye irritation potential is expected for target substance Pentaerythritol tetrastearate (CAS 115-83-3).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are no adequate study data on the skin and eye irritation effects of the target substance Pentaerythritol tetrastearate (CAS 115-83-3). 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) 1907/2006, Annex XI, 1.5. For each specific endpoint source substances 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 62125-22-8

A primary dermal irritation study was performed with 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) according to OECD Guideline 404 and GLP (key study, 1984). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive 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. In two animals very slight erythema and very slight oedema was observed 1 hour after treatment. Effects were fully reversed within 24 hours after treatment. The third animal was free of any skin irritation effect. Individual mean oedema and erythema scores over 24, 48 and 72 hour were 0.0 in all three animals. The test material is not considered irritating to the skin in this study.

In a second primary dermal irritation study performed according to OECD guideline 404 (supporting study, 1997) the skin of three male New Zealand rabbits was exposed to the test material for 4 hours. Skin reactions were assessed 1, 24, 48 and 72 hour 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. Individual mean erythema scores over 24, 48 and 72 hour were 1.3, 0, and 0.3 for animal #1, #2, and #3, respectively. All treated skin sites appeared normal at the 72 hour observation. Individual mean oedema scores over 24, 48 and 72 hour were 0.0 in all three animals. Based on the results of this study, the test substance is not considered to be skin irritating.

 

CAS 68424-31-7

In a primary skin irritation study with Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7), which was performed according to OECD Guideline 404 (supporting study, 1991), the shaved skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test substance for 4 hours under semi-occlusive 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 oedema (grade 1) in all animals 24 hours after removal of the test substance. The effects were fully reversible 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 individual mean erythema score over 24, 48 and 72 hours were 1.3, 1.3, and 1.7. The individual mean oedema score over 24, 48 and 72 hours were 0.3 for all three animals. All treated skin sites appeared normal at the 96 hour observation. Based on the results of this study, the test substance is not considered to be skin irritating.

 

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) (supporting study, 1999). The clipped skin of three female New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive 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 individual mean erythema scores over 24, 48 and 72 hours were 0.0, 0.0 and 0.33. No oedema 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 dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) comparable to OECD guideline 404 and under GLP conditions (supporting study, 1995). The shaved skin of six male New Zealand White rabbits was exposed to 0.5 mL unchanged test material for 4 hours under semi-occlusive conditions. Skin reactions were assessed 1, 24, 48 and 72 hours after removal of the test substance. No erythema and no oedema occurred in any of the tested animals at any reading time point. At the 72 hour time point two animals showed desquamation. Individual mean oedema and erythema scores over 24, 48 and 72 hour were 0.0 in all six animals. The test material is not considered irritating to the skin in this study.

 

Eye irritation

 

CAS 62125-22-8

In a study performed comparable to OECD Guideline 405 (key study, 1982) 0.1 mL of undiluted 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) was applied into the conjunctival sac of six female New Zealand White rabbits each. 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 hours 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 hour 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. Individual cornea opacity and iris scores over 24, 48 and 72 hour were 0.0 in all six animals. Individual mean chemosis scores over 24, 48 and 72 hour were 0.0 (n=2) and 0.3 (n=4). Individual mean conjunctivae scores over 24, 48 and 72 hour were 0.33 (n=2), 0.67 (n=2), 1.0 (n=1) and 1.33 (n=1). Thus, the test material is not considered irritating to the eyes in this study.

 

CAS 62125-22-8

In a second in vivo study performed comparable to OECD Guideline 405 (supporting study, 1997) the test material was applied into the conjunctival sac of three male New Zealand rabbits each. The animals were observed for 72 hours and reactions were assessed 1, 24, 48, 72 hour and 7 days after instillation according to the Draize scoring system. No data on chemosis were provided in this study. 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. Individual cornea opacity and iris scores over 24, 48 and 72 hour were 0.0 in all three animals. Individual mean conjunctivae scores over 24, 48 and 72 hour were 0.11, 0.11 and 0.0. 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 guideline 405 (supporting study, 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. Conjunctival effects included slight redness (1 animal) and slight discharge (1 animal) and were transiently seen approximately 1 hour after dosing. Individual cornea opacity, iris, conjunctivae and chemosis scores over 24, 48 and 72 hour were 0.0 in all three animals. Thus, the test material is 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 guideline 405 (supporting study, 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 conjunctival redness. All three animals exhibited severe discharge. No iridial or corneal changes were evident throughout the study. At 24 hours post treatment, one animal was free of conjunctival redness. All three animals were free of ocular irritation within 72 hours after treatment. Individual cornea opacity, iris, and chemosis scores over 24, 48 and 72 hour were 0.0 in all three animals. Individual conjunctivae scores over 24, 48 and 72 hour were 0.67 in all three animals. 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 dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) was tested for its acute eye irritation potential in a study performed comparable to OECD Guideline 405 under GLP conditions (supporting study, 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. Fluorescein staining of the cornea was observed in three animals at the 48 hour reading time point. At the 72 hour reading, no staining of the cornea was observed indicating that the corneal response was superficial and transient. Individual cornea opacity, iris and chemosis scores over 24, 48 and 72 hour were 0.0 in all six animals. Individual mean conjunctivae scores over 24, 48 and 72 hour were 0.67 (n=4) and 1.0 (n=2). Thus, the test material is not considered irritating to the eyes under the conditions of this study.

 

Overall conclusion for skin and eye irritation

Based on the results of the available studies, none of the source substances is considered to cause either skin or eye irritation or damage. Therefore, on the basis of these findings, no skin and eye irritation potential for the target substance Pentaerythritol tetrastearate (CAS 115-83-3) is identified.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) 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 Pentaerythritol tetrastearate (CAS 115-83-3), 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.