Fatty acids, C16-18, isononyl esters

Endpoint summary

Description of key information

Skin, rabbit (OECD 404): not irritating (read-across)

Eye, rabbit (OECD 405): not irritating (read-across)

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:

11 - 18 Mar 1991

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Analytical purity of test substance not given, occlusive exposition according to former guideline, lack of detailed reporting.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

yes

Remarks:

occlusive exposition according to former guideline, analytical purity of test substance not specified, lack of detailed reporting;

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2285 g
- Date of reception: Februar 19th, 1991

Type of coverage:

occlusive

Preparation of test site:

not specified

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:

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

Number of animals:

3

Details on study design:

SCORING SYSTEM: According to Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48h

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

When administered occlusive for 4h to rabbit skin, the test substance caused only slight irritations in one animal after 24h that were fully reversible within 48h.

Erythema Score

Animal Number	1 h	24 h	48 h	72 h
1	0	0	0	0
2	1	0	0	0
3	2	1	0	0

 

Edema Score

Animal Number	1 h	24 h	48 h	72 h
1	0	0	0	0
2	1	0	0	0
3	2	1	0	0

 

Interpretation of results:

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

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

April 1994

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Basic data given. Data on analytical purity, animal husbandry and the dose applied are missing.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1992

Deviations:

yes

Remarks:

data on analytical purity, animal husbandry and dose applied are missing

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

not specified

Controls:

other: untreated sites of the same animal served as control

Duration of treatment / exposure:

4 h

Observation period:

5 days
Reading time points: 1, 24, 48 and 72 h, and 5 days

Number of animals:

3 males

Details on study design:

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

5 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 h

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

5 days

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 5 days

Irritant / corrosive response data:

3/3 animals had very slight erythema (grade 1) 1 hour after exposure ended. Very slight oedema (grade 1) was observed in 1/3 rabbits from the 1-hour- up to and including the 72-hour reading time point, while 2/3 did not have edema at any reading time point. At the 24-hour reading time point 2/3 animals still had very slight erythema and 1/3 had well defined erythema. The erythema cleared in 1/3 animals within 48 hours and in the remaining 2 within 5 days. All irritation reactions were completely reversible within 5 days.

Table 1: Erythema and edema scores for the individual animals:

Animal No.	Reading time point	Erythema score	Edema score
1	1 h	1	0
	24 h	1	0
	48 h	1	0
	72 h	1	0
	5 d	0	0
2	1 h	1	0
	24 h	1	0
	48 h	0	0
	72 h	0	0
	5 d	0	0
3	1 h	1	1
	24 h	2	1
	48 h	1	1
	72 h	1	1
	5 d	0	0

Interpretation of results:

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

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

23 Jun - 30 Jun 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The exposure was done under occlusive conditions, few details on the test substance were given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 1981

Deviations:

yes

Remarks:

occlusive exposure, lack of details on test substance

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

occlusive exposure, lack of details on test substance

GLP compliance:

yes

Species:

rabbit

Strain:

other: Kleinrusse, Chbb:HM

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Fa. Thomae, Biberach, Germany
- Weight at study initiation: 2442 g (average)
- Housing: single housing in rabbit cages, (Fa. Heinkel, Kuchen, Germany)
- Diet: feed 20 ZH 5 (Fa. Nohrlin GmbH, Bad Salzuflen, Germany)
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

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

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated skin served as the 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 days
Reading time points: 1, 24, 48 and 72 h, and 7 days

Number of animals:

5 males

Details on study design:

TEST SITE
- Area of exposure: dorsal skin, an approximately 2.5 cm x 2.5 cm area
- Type of wrap if used: a 2.5 cm x 2.5 cm gauze patch with the test substance was applied to the skin of the rabbit. The gauze patch was covered by a plastic film, which was fixed with adhesive tapes; then finally an acrylastic band (occlusive) was applied. During the 4-hour exposure the animals were kept in special boxes to ensure the wrapping did not move.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported

SCORING SYSTEM: Draize scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

mean after

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritant / corrosive response data:

No irritation effects were observed 1 hour after exposure ended. At the 24-hour reading time point, 3/5 animals had very slight erythema and edema. By the 48-hour reading time point, the severity had increased to well-defined erythema in 2/5 animals, while 2/5 had very slight erythema. 2 of these rabbits also had very slight edema, which was still present at the 72-hour reading time point. Very slight to well-defined erythema persisted in 3/5 rabbits until 72 hours after exposure. All the irritation effects had cleared completely within 7 days.

   

Table 1: Individual skin irritation scores

	Rabbit 1		Rabbit 2		Rabbit 3		Rabbit 4		Rabbit 5
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
1 h	0	0	0	0	0	0	0	0	0	0
24 h	1	1	0	0	1	1	1	1	0	0
48 h	1	0	1	0	2	1	2	1	0	0
72 h	1	0	0	0	1	1	2	1	0	0
7 days	0	0	0	0	0	0	0	0	0	0
Mean value 24 + 48 + 72 h	1	0.33	0.33	0	1.33	1	1.67	1	0	0
Mean value 24 + 48 + 72 h all animals	0.87	0.47

           

 

Interpretation of results:

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

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

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

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 after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

72 h

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

erythema score

Basis:

animal #4

Remarks:

mean after

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

erythema score

Basis:

animal #5

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 h

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

edema score

Basis:

animal #4

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

7 days

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

edema score

Basis:

animal #5

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

5 days

Remarks on result:

other:

Remarks:

Source: CAS 3687-46-5

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 h

Remarks on result:

other:

Remarks:

Source: CAS 3687-46-5

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

5 days

Remarks on result:

other:

Remarks:

Source: CAS 3687-46-5

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

Source: CAS 3687-46-5

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

Source: CAS 3687-46-5

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other:

Remarks:

5 days

Remarks on result:

other:

Remarks:

Source: CAS 3687-46-5

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

Source: CAS 26399-02-0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

Source: CAS 26399-02-0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 h

Remarks on result:

other:

Remarks:

Source: CAS 26399-02-0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

Source: CAS 26399-02-0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other:

Remarks:

not applicable

Remarks on result:

other:

Remarks:

Source: CAS 26399-02-0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

48 h

Remarks on result:

other:

Remarks:

Source: CAS 26399-02-0

Interpretation of results:

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

Conclusions:

The available data on suitable source substances did not show any skin irritation effects. Therefore, the target substance Fatty acids, C16-18, isononyl esters is not predicted to be a skin irritant.

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:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Test substance purity not specified, methodological differences, only 0.05 mL test substance evaluated, only 24-h reading, only 24-h observation period.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

test substance purity not specified, methodological differences, only 0.05 mL test substance evaluated, only 24-h reading, only 24-h observation period

GLP compliance:

no

Species:

rabbit

Strain:

other: New Zealand

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated left eye served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 mL undiluted test substance

Duration of treatment / exposure:

single eye instillation

Observation period (in vivo):

24 hours

Reading time points: 2, 6 and 24 h after instillation

Number of animals or in vitro replicates:

2 (male)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): no data

SCORING SYSTEM: Draize scoring system

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2

Remarks:

mean of reading at

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

iris score

Basis:

animal: #1, #2

Remarks:

mean of reading at

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #2

Remarks:

mean of reading at

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Remarks on result:

not determinable because of methodological limitations

Irritation parameter:

chemosis score

Basis:

animal: #1, #2

Remarks:

mean of reading at

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Remarks on result:

not determinable because of methodological limitations

Irritant / corrosive response data:

One animal showed mild conjunctival erythema 2 hours after instillation, which disapperaed completely within 6 hours.

Interpretation of results:

other: The results of this study can only be read together with other source substance data.

Conclusions:

The test substance was not irritating in this test, however, only 0.05 mL test substance evaluated and only 24-h reading.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

26 - 31 May 1999

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

The analytical purity of the test substance was not specified.

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

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: ESD (Chatillon sur Chalaronne, France)
- Weight at study initiation: 2-2.5 kg
- Housing: animals were housed individually in high impact polystyrene cages with a mesh floor
- Diet: Food ref. 112 (U.A.R., Epinay sur Orge, France)
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 30-80
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 26 May 1999 To: 31 May 1999

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):

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

Number of animals or in vitro replicates:

3 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not washed

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: After instilling 2% fluorescein into the eyes, any damage was assessed with a UV-lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

out of all 3 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

out of all 3 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

out of all 3 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

out of all 3 animals / mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritant / corrosive response data:

At the 1-hour reading time point, 3/3 rabbits had slight-moderate conjunctivae (scores 1, 1, 2) and 2/3 slight chemosis (scores 0, 1, 1). The chemosis had cleared by the 24-hour reading time point, while 3/3 animals still had slight conjunctivae (scores 1, 1, 1). All eye irritation effects were fully reversible within 48 hours.

Table 1: Eye irritation score

Rabbit #	Time [h]	conjunctivae		iris	cornea
		redness	swelling
1	1	1	0	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
2	1	2	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0
3	1	1	1	0	0
	24	1	0	0	0
	48	0	0	0	0
	72	0	0	0	0
	average	0.33	0.0	0.0	0.0

Interpretation of results:

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

Reference 3

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

10 Jul - 17 Jul 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Few details on the test substance were given.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted Feb 1987

Deviations:

yes

Remarks:

lack of details on test substance

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

lack of details 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: Fa. Thomae, Biberach, Germany
- Weight at study initiation: 2245 g (average)
- Housing: single housing in rabbit cages, (Fa. Henkel, Kuchen, Germany)
- Diet: Altromin feed 2023 (Fa. Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

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

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served as the 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):

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

Number of animals or in vitro replicates:

4 males

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated eye was not washed

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp and fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of all 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Remarks:

of all 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of all 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of all 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

1 hour after instilling the test substance in the eyes, 1/4 rabbits had a slight discharge (grade 1 of 3) and 2/4 severe discharge (grade 3) from the treated eye, while 3/4 rabbits showed slight redness of the eye (grade 1 of 3). At the 6-hour reading time point, 3/4 rabbits showed slight redness and 1/4 still had severe discharge from the eye. These effects cleared completely within 24 hours and none of the animals had eye irritation effects at reading time points 24, 48 and 72 hours.

Interpretation of results:

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

Reference 4

Endpoint:

eye irritation: in vivo

Type of information:

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

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:

mean

Remarks:

of 3 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 72576-80-8

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 72576-80-8

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 72576-80-8

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 3 animals / mean after

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

other:

Remarks:

Source: CAS 72576-80-8

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 4 animals / mean after

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Remarks on result:

other:

Remarks:

Source: CAS 95912-88-2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 2 animals

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

not determinable because of methodological limitations

Remarks:

Source: CAS 91031-48-0

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 2 animals

Time point:

24 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

not determinable because of methodological limitations

Remarks:

Source: CAS 91031-48-0

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 2 animals

Time point:

24 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

not determinable because of methodological limitations

Remarks:

Source: CAS 91031-48-0

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 2 animals

Time point:

24 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

not determinable because of methodological limitations

Remarks:

Source: CAS 91031-48-0

Interpretation of results:

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

Conclusions:

The available data on suitable source substances did not show any eye irritation effects. Therefore, the target substance Fatty acids, C16-18, isononyl esters is not predicted to be a eye irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Read across justification

There are no adequate study data on the skin and eye irritation effects of Fatty acids, C16-18, isononyl esters (CAS 91031-57-1). 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 95912-88-2

In a study according to OECD guideline 404 (WoE, 1987) with Fatty acids, C16-18, isotridecyl esters only slight oedema and slight to moderate erythema (Draize scoring system) was reported in 5 rabbits after 4 hours of exposure to 0.5 mL of the unchanged liquid test substance under occlusive conditions. The erythema and oedema were fully reversible within 7 days. No indication of skin irritation was found.

CAS 3687-46-5

A skin irritation study equivalent to OECD guideline 404 (WoE, 1994) was performed with Decyl oleate (CAS 3687-46-5). 0.5 mL of the liquid test substance was applied to the shaved skin of 3 male rabbits for 4 hours of exposure under semi-occlusive conditions. Only slight erythema and edema was seen at the 48 and 72 hour readings. All findings were fully reversible within 5 days. No indication of irritation to skin was found for the test substance.

 

CAS 26399-02-0

A skin irritation study equivalent to OECD guideline 404 (WoE, 1991) was performed with 2-ethylhexyl oleate (CAS 26399-02-0). 0.5 mL of the liquid test substance was applied to the skin of 3 rabbits for 4 hours of exposure under occlusive conditions. Slight erythema and edema was seen in only one out of 3 animals at the 24 hour readings. All findings were fully reversible within 48 hours. No indication of irritation to skin was found for the test substance.

Eye irritation

CAS 95912-88-2

A study according to OECD guideline 405 (WoE, 1987) was done with Fatty acids, C16-18, isotridecyl esters. No eye irritation was seen after single instillation of 0.1 ml unchanged test substance without washing to one eye of 4 rabbits. Draize scores for cornea opacity, iris, conjunctivae and chemosis scores were 0 at the 24, 48, and 72 hour readings in all animals. Under the conditions of the study, the test substance showed no eye irritating potential.

 

CAS 3687-46-5

Hexadecanoic acid, isooctadecyl ester (CAS 72576-80-8) was examined for its eye irritation potential in a GLP study performed according to OECD guideline 405 (WoE, 1999). 0.1 mL of unchanged liquid test substance was instilled into one eye of 3 rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. At the 24-hour reading time point 3/3 rabbits had slightly reddened conjunctivae (score 1), which was fully reversible within 48 hours. No other eye irritation effects were observed in any rabbit at any time point. Under the conditions of the study, the test substance showed no eye irritating potential.

CAS 91031-48-0

Fatty acids, C16-18, 2-ethylhexyl esters (CAS 91031-48-0) was examined for its eye irritation potential in a study performed similar to OECD guideline 405 (WoE, 1978). 0.05 mL of unchanged liquid test substance was instilled into one eye of 2 rabbits. The animals were observed for 24 hours and scoring according to Draize was performed 2, 6, and 24 hours after instillation. One animal showed mild conjunctival erythema 2 hours after instillation, which disapperaed completely within 6 hours. At the 24-hour reading no eye irritation effects were seen in any of the 3 rabbits.

 

Overall conclusion for skin and eye irritation

The available data for analogue read across substances indicate absence of any skin or eye irritation potential. Therefore, no skin or eye irritation potential is anticipated for the target substance Fatty acids, C16-18, isononyl esters (CAS 91031-57-1).

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 Fatty acids, C16-18, isononyl esters (CAS 91031-57-1), 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.