Fatty acids, C8-10, oxybis(2-hydroxy-3,1-propanediyl) esters

Endpoint summary

Description of key information

Skin irritation (OECD 404): not irritating

RA from source substance (CAS 130905-60-1)

Skin irritation (similar to OECD 404 and Human Patch Test): not irritating

RA from source substance (CAS 63705-03-3)

Eye irritation (OECD 405): not irritating

RA from source substance (CAS 130905-60-1)

Eye irritation (similar to OECD 405): not irritating

RA from source substance (CAS 63705-03-3)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

16 - 20 August 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted in 1981

Deviations:

yes

Remarks:

analytical purity not reported

GLP compliance:

yes

Remarks:

Bezirksregierung, Lüneburg, Germany

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm, Bremervörde, Germany
- Weight at study initiation: 2.4 – 2.8 kg
- Housing: individual housing in a battery of cages, each equipped with a paper roll disposal system
- Diet: Ssniff MÜ ZR (Alleindiät für Zuchtkaninchen), pellets, ad libitum
- Water: drinking water as for human consumption, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 2 °C
- Humidity (%): 50 -85%
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated sites of the same animal served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

3 days
Reading time points. 30- 60 min, 24, 48 and 72 h

Number of animals:

3 (sex not reported)

Details on study design:

TEST SITE
- Area of exposure: 6 cm² on the back of each animal
- Type of wrap if used: The treated skin was covered with a semiocclusive dressing consisting of Kosmoplast R (Medilog), held in place by non-irritating tape Elastoplast R and Stülpa.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed with water or an appropriate solvent
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 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:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Interpretation of results:

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

Conclusions:

CLP: not classified

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Lack of data on test material. Occlusive conditions.

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrusse, Chbb:HM

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: adult
- Weight at study initiation: 2.3 kg
- Housing: The animals were single housed in rabbit cages.
- Diet: 20 ZH 5, Nohrlin GmbH
- Water: tap water, ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 45 - 50
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

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(s) applied (volume or weight with unit): 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

7 d
Reading time points: 1, 24, 48 and 72 h and 7 d

Number of animals:

4 males

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm² on the dorsal area of the trunk
- Type of wrap if used: The treated skin was covered with a plastic film, held in place with adhesive plasters and acrylastic tape.

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

other: mean out of all 4 animals

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

other: mean out of all 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

The dermal application of the test substance did not result in edema in any of the animals tested at any observation time point. Very slight to slight erythema formation was observed in 3/4 animals at the 24 and 48 h reading time points. At the 72 h reading time point, slight and moderate erythema formation was observed in 2/4 animals. The effects were reversible in all animals within 7 d after the application of the test substance.

Table 1. Results of skin irritation study

Observation time	Rabbit no.
	1		2		3		4
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	0	0	1	0	0	0	1	0
24 h	0	0	1	0	1	0	2	0
48 h	0	0	1	0	1	0	2	0
72 h	0	0	0	0	1	0	3	0
7 d	0	0	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	0.00	0.00	0.67	0.00	1.00	0.00	2.33	0.00
Mean value 24 + 48 + 72 h all animals	1.00	0.00

Interpretation of results:

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

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 1987

Deviations:

yes

Remarks:

no analytical purity reported

GLP compliance:

yes

Remarks:

Bezirksregierung, Lüneburg, Germany

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harald Schriever, Kaninchenfarm, Bremervörde, Germany
- Weight at study initiation: 2.4 – 2.8 kg
- Housing: individual housing in a battery of cages, each equipped with a paper roll disposal system
- Diet: Ssniff MÜ ZR (Alleindiät für Zuchtkaninchen), pellets, ad libitum
- Water: drinking water as for human consumption, ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 2 °C
- Humidity (%): 50 -85%
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye was used as control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

24 h (single application without washing)

Observation period (in vivo):

5 days
Reading time points. 30- 60 min, 24, 48 and 72 h

Number of animals or in vitro replicates:

3 (sex was not reported)

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals

Time point:

24/48/72 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:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 5 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

Some definitely hyperhemic blood vessels (grade 1 conjunctival redness) was observed 1 h post treatment in all 3 animals and in 2/3 animals at 24, 48 and 72 h post treatment. In 1/3 animals this reaction was augmented, as diffuse, crimson colour, not easily discernible individual vessels (grade 2 conjunctival redness) were observed at the 24 h reading time point. 48 and 72 h post treatment only a conjunctival redness, graded 1, was observed. Chemosis was observed in 2/3 animals (grade 1 conjunctival chemosis) at 24 h post treatment, which was fully reversible within 48 h post treatment. All above mentioned effects resulted to be fully reversible latest within 5 days post treatment.

Other effects:

No further effects occurred.

Interpretation of results:

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

Conclusions:

CLP: not classified

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Lack of data on test substance.

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrusse, Chbb:HM

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Thomae, Biberach, Germany
- Age at study initiation: adult
- Weight at study initiation: 2.5 kg
- Housing: The animals were single housed in rabbit cages.
- Diet: Altromin 2023, ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 7 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 21
- Humidity (%): 45 - 55
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

3 d
Reading time points: 1, 6, 24, 48 and 72 h

Number of animals or in vitro replicates:

4 males

Details on study design:

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

other: mean out of all 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

other: mean out of all 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

other: mean out of all 4 animals

Time point:

24/48/72 h

Score:

0.08

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

other: mean out of all 4 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritant / corrosive response data:

The application of the test substance to one eye of each animal did not result in corneal opacity, iritis or swelling of the conjunctivae at any observation time point. Very slight redness of the conjunctivae was observed in 1/4 animals at the 24 h reading time point. The effect was reversible within 48 h after the application of the test substance.

Interpretation of results:

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

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

Irritation

Justification for read-across

There is no data available regarding skin or eye irritation for the target substance Fatty acids, C8-10, oxybis(2-hydroxy-3,1-propanediyl) esters (CAS 92044-91-2). Therefore, read across from the relevant source substances Hexanedioic acid, mixed esters with decanoic acid, 12 -hydroxyoctadecanoic acid, isostearic acid, octanoic acid, 3,3'-oxybis[1,2-propanediol] and stearic acid (CAS 130905-60-1) and 1,2,3-Propanetriol, homopolymer, diisooctadecanoate (CAS 63705-03-3) was applied to obtain information regarding irritating or corrosive potential.

Read-across from appropriate substances is conducted in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. in order to fulfil the standard data requirements defined in Regulation (EC) No 1907/2006, Annex VIII, 8.1 and 8.2. 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 130905-60-1

A skin irritation study was performed with the test substance according to OECD guideline 404 (Sasol, 1990). The clipped skin of the back of 3 New Zealand White rabbits was exposed to 0.5 mL of the test substance for 4 h under semiocclusive conditions. The rabbits were observed for 3 days. Skin reactions were assessed using the Draize scoring system 30 - 60 min, 24, 48 and 72 h after patch removal. The mean scores for erythema and edema (24/48/72 h) were 0.0, indicating that the test substance is not irritating to the skin.

CAS 63705-03-3

A skin irritation study was performed with the test substance equivalent or similar to OECD guideline 404 (BASF, 1988). The shaved skin of the back of 4 male rabbits (Kleinrusse) was exposed to 0.5 mL of the undiluted test substance for 4 h under occlusive conditions. The rabbits were observed for 7 days. Skin reactions were assessed using the Draize scoring system 1, 24, 48 and 72 h and 7 d after patch removal. Very slight to slight erythema formation was observed in 3/4 animals at the 24 and 48 h reading time points. At the 72 h reading time point, slight and moderate erythema formation was observed in 2/4 animals. The mean score for erythema (24/48/72 h) was 1.0, which was fully reversible within 7 days and for edema (24/48/72 h) 0.0. These results indicate that the test substance is not irritating to the skin.

There is data from a Human Patch Test similar to the Guidelines for the Assessment of Skin Tolerance of Potentially Irritant Cosmetic Ingredients (COLIPA, 1997) (BASF, 1997). The test substance was applied at a concentration of 20% for 24 h onto the backs of 20 volunteers in an occlusive manner. The reading time points were 6, 24, 48 and 72 h after removal of the test substance. Exposure to the test substance led to slight erythema in 3/20 volunteers and slight scaling in 2/20 volunteers. The mean scores after 6, 24, 48 and 72 h were 0.15 for erythema and 0.25 for erythema, edema, scaling and fissure. The skin compatibility of the test substance was enhanced compared to the positive control 1% Texapon N25 and 0.5% SDS.

Based on the available human data the test substance is considered not to be irritating to the skin.

 

Eye irritation

CAS 130905-60-1

An eye irritation study was performed with the test substance according to OECD guideline 405 (Sasol, 1990). 3 New Zealand White rabbits were treated with 0.1 mL of the undiluted test substance. The untreated eye served as control and the eyes of the animals were not washed out. The animals were observed for 5 days with reading time points at 30 - 60 min, 24, 48 and 72 h after application. The application of the test substance to one eye of each animal did not result in corneal opacity or iritis at any observation time point.  Some definitely hyperhemic blood vessels (grade 1 conjunctival redness) was observed 1 h post treatment in all 3 animals and in 2/3 animals at 24, 48 and 72 h post treatment. In 1/3 animals this reaction was augmented, as diffuse, crimson colour, not easily discernible individual vessels (grade 2 conjunctival redness) were observed at the 24 h reading time point. 48 and 72 h post treatment only a conjunctival redness, graded 1, was observed. Chemosis was observed in 2/3 animals (grade 1 conjunctival chemosis) at 24 h post treatment, which was fully reversible within 48h post treatment. All above mentioned effects resulted to be fully reversible latest within 5 days post treatment. In conclusion, mean cornea opacity and iris scores of 0.0, a mean conjunctivae score of 1.11 and a mean chemosis score of 0.22 were obtained. Based on these results the test substance is not regarded as eye irritant.

CAS 63705-03-3

An eye irritation study was performed with the test substance equivalent or similar to OECD guideline 405 (BASF, 1988). 4 male rabbits (Kleinrusse) were treated with 0.1 mL of the undiluted test substance. The untreated eye served as control and the eyes of the animals were not washed out. The animals were observed for 3 days with reading time points at 1, 6, 24, 48 and 72 h after application. The application of the test substance to one eye of each animal did not result in corneal opacity, iritis or swelling of the conjunctivae at any observation time point. Very slight redness of the conjunctivae was observed in 1/4 animals at the 24 h reading time point. The effect was reversible within 48 h after the application of the test substance. Thus, mean scores of cornea opacity, iris and chemosis of 0.0 was obtained and a mean conjunctivae score of 0.08. Based on these results the test substance is not regarded as eye irritant.

The available data on skin and eye irritation after application of the two analogue substances (CAS 130905-60-1 and CAS 63705-03-3) do not meet the criteria for classification according to Regulation (EC) 1272/2008.

Justification for classification or non-classification

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.