Lauric acid, ester with hydroxypropanediyl diacetate

Endpoint summary

Description of key information

Skin, rabbit: not irritating
Eye, rabbit: 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:

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

Adequacy of study:

key study

Study period:

20 - 23 Nov 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-Guideline study, tested with the source substance Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (CAS 97593-30-1). According to the ECHA guidance document 'Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-aross substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Species:

rabbit

Strain:

other: Crl:KBL(NZW)BR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kißlegg, Germany
- Age at study initiation: young adults
- Weight at study initiation: 3.1-3.5 kg
- Housing: individually in cage units Metall/Noryl. Excrement trays below the cages contained low dust wood granulate bedding. The wood granulate was changed at least twice weekly. The animals were regularly transferred to clean cages. The animal room was provided with sound from a radio program.
- Diet: standard diet "Ssniff K-Z" 4mm (Ssniff Spezialdiäten GmbH, Soest, Germany), approx. 100 g per animal per day. To satisfy the needs of roughage, hay was offered additionally (hay, irradiated, delivered by Harlan Winkelmann, Borchen, Germany; respectively hay pellets delivered by Ssniff Spezialdiäten GmbH, Soest, Germany).
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 25
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

Initial test: 3 min, 1 and 4 h
Confirmatory test: 4 h

Observation period:

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: approx. 2.5 cm by 2.5 cm on the dorso-lateral areas of the trunk
- Type of wrap if used: the treated skin was covered with a gauze patch, held in place with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the exposed skin area was carefully washed with water without altering the existing response or the integrity of the epidermis.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

TESTING PROCEDURE
- Initial test: due to a possible irritant potential of the test substance, in the first step only one animal was used and three patches were applied successively to this animal. The first patch was removed after 3 min. As no serious skin reactions were observed, the second patch was applied and removed after 1 h. At this stage, the observations indicated that with respect to animal welfare the exposure can be allowed to extend to 4 h. Therefore, the third patch was applied and removed after 4 h and the responses were graded 1 h later.
- Confirmatory test: the test was completed using two additional animals exposed for 4 h.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Initial test
In the first animal, no skin reactions were observed immediately after patch removal following 3 min and 1 h of exposure, respectively.

Confirmatory test
1 h post-application: very slight erythema was observed in 2/3 animals, being fully reversible in one animal at the 24 h reading. No edema was noted in any animal.
24-48 h post-application: very slight erythema was observed in 1/3 animals at both reading time points, being fully reversible at the 72 h reading. No edema was noted in any animal.
72 h post-application: No skin reactions were observed in any animal.

Other effects:

No further local effects were reported. There were no systemic intolerance reactions.

Table 1. Results of skin irritation study.

Observation time	Rabbit no.
	1		2		3
	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	1	0	0	0	1	0
24 h	1	0	0	0	0	0
48 h	1	0	0	0	0	0
72 h	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	0.67	0.00	0.00	0.00	0.00	0.00

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

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:

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

Adequacy of study:

key study

Study period:

27 - 30 Nov 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP-Guideline study, tested with the source substance Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (CAS 97593-30-1). According to the ECHA guidance document 'Practical guide 6: How to report read-across and categories' (ECHA, 2012), the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-aross substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Ministerium für Umwelt und Naturschutz, Landwirtschaft und Verbraucherschutz des Landes Nordrhein-Westfalen, Düsseldorf, Germany

Species:

rabbit

Strain:

other: Crl:KBL(NZW)BR

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Kißlegg, Germany
- Age at study initiation: young adults
- Weight at study initiation: 3.1-3.5 kg
- Housing: individually in cage units Metall/Noryl. Excrement trays below the cages contained low dust wood granulate bedding. The wood granulate was changed at least twice weekly. The animals were regularly transferred to clean cages. The animal room was provided with sound from a radio program.
- Diet: standard diet "Ssniff K-Z" 4mm (Ssniff Spezialdiäten GmbH, Soest, Germany), approx. 100 g per animal per day. To satisfy the needs of roughage, hay was offered additionally (hay, irradiated, delivered by Harlan Winkelmann, Borchen, Germany; respectively hay pellets delivered by Ssniff Spezialdiäten GmbH, Soest, Germany).
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 25
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

72 h
Reading time points: 1, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean over 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: mean over 24, 48 and 72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

1 h post-instillation: moderate conjunctival redness and very slight chemosis were observed in all 3 animals. No corneal opacity or iritis was noted in any animal.
24 h post-instillation: slight conjunctival redness and very slight chemosis were observed in 3/3 and 2/3 animals, respectively. Both effects were fully reversible after further 24 h (48 h reading). No corneal opacity or iritis was noted in any animal.
48-72 h post-instillation: no eye effects were observed in any animal.

Other effects:

No further local effects were reported. There were no systemic intolerance reactions.

Table 1. Results of eye irritation study.

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	2	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.0	0.0	0.0
2	1	2	1	0	0
	24	1	1	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.3	0.0	0.0
3	1	2	1	0	0
	24	1	1	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.3	0.3	0.0	0.0
	Time [h]	conjunctivae		iris	cornea
		redness	swelling
average score	1	2.00	1.00	0.00	0.00
	24	1.00	0.67	0.00	0.00
	48	0.00	0.00	0.00	0.00
	72	0.00	0.00	0.00	0.00
	24+48+72	0.33	0.22	0.00	0.00

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Analogue justification

There are no available data on skin and eye irritation of Lauric acid ester with hydroxypropanediyl diacetate (CAS 30899-62-8). 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

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 (Gmelin, 2008a). 0.5 mL of the undiluted test substance was applied to the dorsal skin of 3 female Crl:KBL(NZW)BR rabbits under semiocclusive 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 test after exposure. In one of these 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 edema occurred in any of the tested animals at any reading time point. No signs of systemic toxicity were observed. The mean erythema and edema scores over the 24, 48 and 72 h reading time points were 0.67, 0 and 0, respectively. The test substance is considered to not be irritating to the skin.

CAS 73398-61-5

The skin irritation potential of Triglycerides, mixed decanoyl and octanoyl was assessed in a study conducted according to OECD guideline 404 and under GLP conditions (Jones, 1988a). 0.5 mL of the undiluted test substance was applied for 4 h to the shaved skin of 6 New Zealand White rabbits, under semiocclusive conditions. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. The test item did not cause any skin reactions at the application site of any animal at any of the reading time points. All erythema and edema scores were 0 for all 6 animals. No signs of systemic toxicity were seen. Therefore, the test substance is considered to be non-irritating to the skin.

Eye irritation

CAS 97593-30-1

An eye irritation study was performed with Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates according to OECD guideline 405 and under GLP conditions (Gmelin, 2008b). 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 and all the scores were 0 for all 3 animals. No further local or systemic toxic effects were observed. The 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.

CAS 73398-61-5

An eye irritation study was performed with Triglycerides, mixed decanoyl and octanoyl according to EPA OPP guideline 81-4 and in compliance with GLP (Jones, 1988b). 0.1 mL of the undiluted test substance was instilled into one eye of 6 New Zealand White rabbits each. The eyes were examined and scored for irritation effects 1, 24, 48 and 72 h after application. At the 1-h reading time point mild to moderate conjunctivae (score 1-2) was observed in 6/6 animals. In 1/6 animals, mild conjunctivae (score 1) was still present 24 h after instillation; the effect was fully reversible within the 48-h reading time point. In the remaining 5/6 animals, the conjunctivae irritation had cleared within 24 h after instillation. Slight to moderate chemosis (score 1-2) was observed in 6/6 rabbits at the1-h reading time point, which persisted in 1/6 animals until 24 h after instillation. For this animal, the effects had cleared completely within 48 h after instillation. For the remaining 5/6 rabbits, the effects had cleared completely within the 24-h reading time point. At the 1-h reading time point, iridial inflammation (score 1) was observed in 1/6 animals. The effect was fully reversible within 24 h. No corneal effects were noted in any animal at any reading time point. No systemic toxic effects were observed. The mean scores for conjunctivae over 24, 48, and 72 h were 0.33, 0, 0, 0, 0 and 0, while the mean scores for chemosis over 24, 48, and 72 h were 0.33, 0, 0, 0, 0 and 0. Therefore, the test substance was not considered to be an eye irritant.

Overall conclusion for skin and eye irritation

The available data on suitable source substances did not show any skin or eye irritation effects. Therefore, the target substance Lauric acid ester with hydroxypropanediyl diacetate is not expected to be a skin irritant or an eye irritant.

Justification for selection of skin irritation / corrosion endpoint:
Hazard assessment is conducted by means of read-across from a structural analogue. The selected study is the most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance 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 a structural analogue. The selected study is the most adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

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 Lauric acid ester with hydroxypropanediyl diacetate (CAS 30899-62-8), data will be generated from 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 and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.