Glycerol trioctanoate

Endpoint summary

Description of key information

In vivo skin irritation (OECD 404, read across): not irritating

In vivo eye irritation (OECD 405, read across): 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:

weight of evidence

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

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean over

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean over

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean over

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

mean over

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

mean over

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

erythema score

Basis:

animal #6

Remarks:

mean over

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean over

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean over

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean over

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

mean over

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

mean over

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 6 days

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

edema score

Basis:

animal #6

Remarks:

mean over

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Source: CAS 620-67-7

The in vivo skin irritation data from the source substance propane-1,2,3-triyl trisheptanoate (CAS 620-67-6) was obtained from a study conducted according to OECD guideline 404 under GLP conditions, and was selected as most suitable within the available source substance data based on study reliability and chemical structure similarity to the target substance. In vivo skin irritation data of two additional substances with similar structure were available and used as source substances in a weight of evidence approach.

Results from additional source substances:

Irritation parameter	Basis	Time point	Score	Max. score	Reversibility	Remarks on results
erythema score	all 6 animals	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 73398-61-5
edema score	all 6 animals	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 73398-61-5
erythema score	animal #1	mean after 24/48/72 h	0.7	4	fully reversible within 72 h	Source: CAS 97593-30-1
erythema score	animal #2, #3	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 97593-30-1
edema score	all 3 animals	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 97593-30-1

Interpretation of results:

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

Conclusions:

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 leading to classification was found in in vivo studies in the rabbit for the source substances triglycerides, mixed decanoyl and octanoyl (CAS 73398-61-5), propane-1,2,3-triyl triheptanoate (CAS 620-67-7), and glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (CAS 97593-30-1). Therefore, no skin irritation potential is expected for target substance glycerol trioctanoate (538-23-8).

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:

weight of evidence

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

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2, #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Source: CAS 620-67-7

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other: Source: CAS 620-67-7

The in vivo eye irritation data from the source substance propane-1,2,3-triyl trisheptanoate (CAS 620 -67 -6) was obtained from a study conducted according to OECD guideline 405 under GLP conditions, and was selected as most suitable within the available source substance data based on study reliability and chemical structure similarity to the target substance. In vivo eye irritation data of two additional substances with similar structure were available and used as source substances in a weight of evidence approach.

Results from additional source substances:

Irritation parameter	Basis	Time point	Score	Max. score	Reversibility	Remarks on results
cornea opacity score	animal #1, #2, #3, #4	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 142-18-7
cornea opacity score	animal #5	mean after 24/48/72 h	1	4	fully reversible within 4 days	Source: CAS 142-18-7
cornea opacity score	animal #6	mean after 24/48/72 h	0.66	4	fully reversible within 72 hours	Source: CAS 142-18-7
iris score	all 6 animals	mean after 24/48/72 h	0	2	reversibility not applicable	Source: CAS 142-18-7
conjunctivae score	animal #1, #6	mean after 24/48/72 h	1.7	3	fully reversible within 4 days	Source: CAS 142-18-7
conjunctivae score	animal #2	mean after 24/48/72 h	1.3	3	fully reversible within 6 days	Source: CAS 142-18-7
conjunctivae score	animal #3	mean after 24/48/72 h	1	3	fully reversible within 72 hours	Source: CAS 142-18-7
conjunctivae score	animal #4	mean after 24/48/72 h	0.3	3	fully reversible within 48 hours	Source: CAS 142-18-7
conjunctivae score	animal #5	mean after 24/48/72 h	2	3	fully reversible within 5 days	Source: CAS 142-18-7
chemosis score	animal #1, #2, #3, #5	mean after 24/48/72 h	1	4	fully reversible within 72-96 hours	Source: CAS 142-18-7
chemosis score	animal #4	mean after 24/48/72 h	0.3	4	fully reversible within 48 hours	Source: CAS 142-18-7
chemosis score	animal #6	mean after 24/48/72 h	1.7	4	fully reversible within 6 days	Source: CAS 142-18-7
cornea opacity score	all 3 animals	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 67593-30-1
iris score	all 3 animals	mean after 24/48/72 h	0	2	reversibility not applicable	Source: CAS 67593-30-1
conjunctivae score	all 3 animals	mean after 24/48/72 h	0.3	3	fully reversible within 48 hours	Source: CAS 67593-30-1
chemosis score	animal #1	mean after 24/48/72 h	0	4	reversibility not applicable	Source: CAS 67593-30-1
chemosis score	animal #2, #3	mean after 24/48/72 h	0.3	4	fully reversible within 48 hours	Source: CAS 67593-30-1

Interpretation of results:

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

Conclusions:

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 in vivo studies in the rabbit for the four source substances propane-1,2,3-triyl triheptanoate (CAS 620-67-7), glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (CAS 97593-30-1), and 2,3-dihydroxypropyl laurate (CAS 142-18-7). Therefore, no eye irritation potential is expected for target substance glycerol trioctanoate (538-23-8).

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

No data on the skin and eye irritation of glycerol trioctanoate (CAS 538-23-8) are 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 620-67-7

A skin irritation study was conducted with propane-1,2,3-triyl triheptanoate (CAS 620-67-6) according to OECD guideline 404 under GLP conditions (WoE, 1993). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of 6 male Small White Russian Chbb:HM rabbits under semi-occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and oedema) was performed 30-60 min, 24, 48 and 72 h as well as 6, 8, 10 and 14 days after removal of the dressing. One animal showed moderate to severe erythema and severe oedema with brown discolouration and dryness of the skin after 24-72 hours. Sanguineous lacerations and scaling were also observed on the skin. At these time points, 4 animals showed no increase in the severity of the described signs of irritation. Moderate redness of the skin was observed in one animal after 72 hours. After 72 hours, this animal also showed dry skin and severe extensive subcutaneous haemorrhage. After 6 days, scaling was observed in all animals, and after 10 to 14 days, all animals were free of abnormalities. The individual mean erythema scores over the 24, 48 and 72 h reading time points were 2.0 (n=4 )2.33, and 3.0. The individual mean oedema scores over the 24, 48 and 72 h reading time points were 2.0 (n=2) 1.0, 4.0, 1.33, and 4.0. All findings were fully reversible within 6 to 14 days. No classification is required according to Regulation (EC) No 1272/2008 for the resulting individual mean erythema and oedema scores obtained from this in vivo study with 6 animals. Thus, the test substance is considered to be non-irritating to the skin.

CAS 73398-61-5

The skin irritation potential of triglycerides, mixed decanoyl and octanoyl was investigated in a study according to OECD guideline 404 (WoE, 1988). The undiluted test substance (0.5 mL) was applied for 4 h to the shaved skin of 6 New Zealand White rabbits under semi-occlusive conditions. The untreated site of the animals served as control. The scoring of skin reactions (erythema and oedema) was performed 24, 48 and 72 h after removal of the dressing. The test item did not elicit any skin reactions at the application site of any animal at any of the observation time points. No signs of systemic toxicity were seen. The mean erythema and oedema scores over the 24, 48 and 72 h reading time points were 0 for all 6 animals.

CAS 97593-30-1

The skin irritation potential of glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated in a study performed according to OECD guideline 404 and under GLP conditions (WoE, 2008). 0.5 mL of the undiluted test substance was applied to the dorsal skin of 3 female Crl:KBL(NZW)BR rabbits under semi-occlusive conditions. In the initial test, one female was exposed to the test substance for 3 min, 1 h and 4 h. As no corrosive effect was observed in the initial test, a confirmatory test was performed using two additional animals treated with the test substance for a period of 4 h. Skin reactions were assessed 1, 24, 48 and 72 h after removal of the test substance. In 2/3 animals, slight erythema (score 1) was observed 1 h after exposure ended. In 1/3 animals the slight erythema persisted until the 48-h reading time point and was fully reversible within 72 h. In the other 2 animals, no erythema was seen 24, 48 and 72 h after patch removal. No oedema was noted in any of the tested animals at any reading time point. No signs of systemic toxicity were observed. The individual mean erythema scores over the 24, 48 and 72 h reading time points were 0.67, 0 and 0, respectively.

Eye irritation

CAS 620-67-7

An eye irritation study was conducted with propane-1,2,3-triyl triheptanoate (CAS 620-67-6) according to OECD guideline 405 under GLP conditions (WoE, 1993). A volume of 0.1 mL of the undiluted test substance was instilled into the eye of 3 male Small White Russian, Chbb:HM rabbits. The untreated contralateral eye served as control. After 24 hours the treated eye was assessed with fluorescein testing and thereafter washed with warm physiological saline. The eyes were examined and scored according to Draize method at 1, 24, 48 and 72 h after instillation. Apart from marked hyperaemia of some blood vessels seen at 1 hour after administration, no eye irritation was observed in any animal at any reading time point. The individual mean scores of readings at 24, 48, and 72 hours for cornea opacity, iris, conjunctivae as well as chemosis were all 0.0 for each of the 3 rabbits.

CAS 142-18-7

An eye irritation study was conducted with 2,3-dihydroxypropyl laurate according to the national FDA guideline "Appraisal of the safety of chemicals in foods, drugs and cosmetics" (WoE, 1977). The solid test material (0.1 g) was placed into the conjunctival sac of the left eye of 6 New Zealand White rabbits each. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 hours as well as 4, 5, 6 and 7 days after application. 24 hours post-application, corneal opacity was observed in 2/6 animals which was fully reversible within 72 and 96 hours, respectively. Slight to moderate conjunctival redness (score 1-2) was observed in all animals at 24 hours, which was fully reversible within 48 hours (n=1), 72 hours (n=1) or 5 days (n=4). Slight to strong discharge was observed in all animals at the 24-hour reading time point, which was fully reversible within 72 hours (n=5) or 4 days (n=1). Test substance application into the rabbit eye induced no iris effects at any reading time point. No local or systemic toxic effects were observed. The individual mean iris score of readings at 24, 48, and 72 hours was 0.0 for all six animals. The individual mean cornea opacity scores were 0.0, 0.0, 0.0, 0.0, 0.66 and 1.0. The individual mean conjunctivae scores were 1.7, 1.3, 1.0, 0.3, 2.0, and 1.7. The individual mean chemosis scores were 0.3, 1.0, 1.0, 1.0, 1.0, and 1.7. Thus, the resulting scores do not lead to classification and therefore the test substance was not considered as eye irritant.

CAS 97593-30-1

An eye irritation study was performed with glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (CAS 97593-30-1) according to OECD guideline 405 under GLP conditions (WoE, 2008). 0.1 mL of the undiluted test substance was installed into one eye of 3 female Crl:KBL(NZW)BR rabbits each. The eye was not rinsed after instillation. Scoring of irritation effects on the eyes was performed 1, 24, 48 and 72 h after test substance application. 1 h after instillation, moderate conjunctival redness (score 2) and very slight chemosis (score 1) were observed in all 3 animals. At the 24-h reading time point slight conjunctival redness (score 1) was observed in 3/3 animals, while very slight chemosis was noted in 2/3 animals. Both conjunctivae and chemosis were fully reversible within the 48-h reading time point. No corneal opacity or iritis was noted in any animal at any reading time point. No systemic toxic effects were observed. The individual mean scores for conjunctivae over 24, 48, and 72 h were 0.33, 0.33 and 0.33, while the mean scores for chemosis over 24, 48, and 72 h were 0, 0.33 and 0.33. The test substance was not considered to be an eye irritant.

Overall conclusion for skin and eye irritation

The available data on source substances did not show any skin or eye irritation effects. Therefore, the target substance glycerol trioctanoate (CAS 538-23-8) is not considered to be a skin irritant or an eye irritant.

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 glycerol trioctanoate (CAS 538-23-8), 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 an analogue 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.