Pentaerythritol tetrastearate

Endpoint summary

Description of key information

GPMT (Read-across, OECD 406): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

challenge (topical): 10 and 25%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No local skin irritation reactions and no signs of systemic toxicity were observed

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

challenge (topical): 10 and 25%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No local skin irritation reactions and no signs of systemic toxicity were observed

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

challenge (topical): 10 and 25%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No local skin irritation reactions and no signs of systemic toxicity were observed

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

challenge (topical): 10 and 25%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

No local skin irritation reactions and no signs of systemic toxicity were observed

Key result

Reading:

other: non concurrent positive control data from Jun-Jul 1999

Group:

positive control

Dose level:

intradermal induction 5% in arachis oil, topical induction 50% in acetone/PEC 400 (70/30); challenge : 50 and 25% in acetone/PEC 400 (70/30)

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

Remarks:

with 2-Mercaptobentothiazole

Data from the source substance Fatty acids C18-C22 (even numbered), tetraesters with Pentaerythritol (CAS 61682-73-3) was selected as key results for reasons of high structural similarity and data reliability. Additional supporting data is given for the source substances 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8, human Repeated Insult Patch Test), Fatty acids, C5-10, esters with pentaerythritol (CAS 68424-31-7, Buehler Test), Fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 67762-53-2, GPMT), and Fatty acids, C8-10 mixed esters with dipentaerythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8, GPMT). No indication of skin sensitisation potential was observed in any of the source substances.

Interpretation of results:

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

Executive summary:

In a guinea pig maximisation test (GPMT) with the structurally highly similar source substance Fatty acids C18-C22 (even numbered), tetraesters with Pentaerythritol (CAS 61682-73-3) no skin sensitising potential was found. No indication for skin sensitising potential was found in any of the supportive data from four source substances. Therefore, no skin sensitisation potential is expected for the target substance Pentaerythritol tetrastearate (CAS 115-83-3).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

There are no in vitro or in vivo data on the skin sensitisation potential of pentaerythritol tetrastearate (CAS 115-83-3). The assessment was therefore based on studies performed with analogue (source) 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).

HUMAN DATA

CAS 62125-22-8

A repeated insult human patch test (RIPT) was conducted to assess the sensitising potential of 2,2-bis[[(1-oxoisooctadecyl)oxy]methyl]-1,3-propanediyl bis(isooctadecanoate) (CAS 62125-22-8) in 55 human volunteers from the general population (supporting study, 1985). Induction was carried out by 10 repeated semi-occlusive applications of the unchanged test substance. Patches were placed on the back of volunteers for 24 hours, followed by a 24 hour rest period (48 hours on weekends). The 10 induction patches were applied to the same site. The induction phase was followed by a resting period of 14 days. Challenge patches were applied to the same site on the back and to a naïve site. Skin reactions were assessed 24 and 48 hours after patch removal. None of the human volunteers showed any skin reactions at the end of the study period. Thus, the test material is not considered sensitising to humans.

ANIMAL DATA

CAS 61682-73-3

A guinea pig maximisation test (GPMT) was performed with Fatty acids C18-C22 (even numbered), tetraesters with Pentaerythritol (CAS 61682-73-3) according to OECD guideline 406 (key study, 2000). A range-finding study was performed for dose selection. 10 albino guinea pigs were treated with the test substance at 1% for intra- and 25% in arachis oil for epidermal induction on days 1 and 7, respectively. 5 animals served as negative controls. A positive control group was not included in the study but information is given on periodical testing of strain sensitivity using 2-Mercaptobentothiazole. 14 days after the epidermal induction, epidermal challenging was performed with 10 and 25% test material dilution in arachis oil. 24 h and 48 hours after challenging skin examination revealed no skin reaction in the test and control groups. Thus, the test material was found to be not sensitising to the skin of guinea pigs, under the conditions of this test.

CAS 68424-31-7

The skin sensitisation potential of Pentaerythritol tetraesters of n-decanoic, n-heptanoic, n-octanoic and n-valeric acids (CAS 68424-31-7) was evaluated in guinea pigs with a Buehler test (supporting study, 1991). Twenty male albino guinea pigs were treated with the test substance and compared with 10 control animals. Three epidermal inductions were performed with 100% test substance in weekly intervals for 6 hours under occlusive conditions. 14 days after the last induction treatment, all animals were challenged for 6 hours epicutaneously with 100% (left shorn flank) and 30% (right shorn flank) test substance (diluted in corn oil) under occlusive conditions. Animals were evaluated for skin reactions 24 h and 48 h after challenge. No signs for irritation or sensitisation were observed during induction and challenge of the animals.

CAS 67762-53-3

A guinea pig maximisation test (GPMT) was performed with Fatty acids, C5-9, tetraesters with pentaerythritol (CAS 67762-53-2) comparable to the OECD guideline 406 (supporting study, 1999). A range-finding study was performed for dose selection. 10 albino guinea pigs were treated with the test substance at 5% for intra- and 100% for epidermal induction on days 1 and 7, respectively. 5 animals served as negative controls. A positive control group was not included in the study but information is given on periodical testing of strain sensitivity using hexylcinnamic aldehyde (HCA). 14 days after the epidermal induction, epidermal challenging was performed with 50 and 100% test material dilution in propylene glycol. 24 h and 48 hours after challenging skin examination revealed no skin reaction in the test and control groups. Thus, the test material was found to be not sensitising to the skin of guinea pigs, under the conditions of this test.

CAS 189200-42-8

A guinea pig maximisation test was performed with Fatty acids, C8-10 mixed esters with dipenaterythritol, isooctanoic acid, pentaerythritol and tripentaerythritol (CAS 189200-42-8) similar to OECD guideline 406 (supporting study, 1995). A range-finding study was performed for dose selection. 20 female Hartley albino guinea pigs were treated with the test substance at 5% for intra- and 100% for epidermal induction on days 1 and 7, respectively. 10 animals served as negative controls. A positive control group treated with 2 -mercaptobenzothiazole (MBT) (intradermal induction: 3%, epicutaneous induction: 25%, challenge: 0.5%) was included in the study which showed 100% sensitising reactions. 14 days after the epidermal induction, epidermal challenging was performed with a 50% test material solution in peanut oil. At the first reading, 24 hours after challenge, skin examination revealed irritation reactions in the test group for 18 of 20 animals and in the control group for 9 of 10 animals. 48 hours after challenge, 7 animals in test and control group each showed skin irritation reactions. Since the 50% challenge concentration resulted in skin irritation, a re-challenge was done using 10% test substance. 5 of 10 control animals (50%) and 4 of 20 (20%) test group animals showed skin irritation 24 hours after re-challenge. All skin reactions were completely reversed 48 hours after re-challenge in both groups. Thus, the test material was found to be not sensitising to the skin of guinea pigs, when used as 5% solution for induction and 10% solution for challenge.

Overall conclusion for skin sensitisation

Several reliable studies performed with analogue source substances are available investigating the skin sensitisation potential both in animals as well as in humans. All data indicate no potential for skin sensitisation in adequate GPMT, Buehler and human repeated insult patch tests. Thus, no hazard for skin sensitisation is identified for the target substance pentaerythritol tetrastearate (CAS 115-83-3).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

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 physico-chemical, 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.

Therefore, based on the analogue read-across approach, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.