Octadecyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Endpoint summary

Description of key information

The test substance caused slight transient edema and erythema after 24h occlusive application onto intact and damaged rabbit skin (Ciba-Geigy 1982) and does not meet the criteria for being classified as a skin irritant. Transient chemosis and conjunctivae findings were observed in rabbits using a procedure similar to OECD testing guideline 405 (Ciba-Geigy 1982).

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 22,1982 - March 2,1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to OECD guideline with acceptable restrictions (24 h exposure, occlusive dressing)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Occlusive dressing, 24 h exposure

Qualifier:

according to guideline

Guideline:

EPA OPP 81-5 (Acute Dermal Irritation)

Principles of method if other than guideline:

The procedure used is described in the Proposed Guidelines of the United States Environmental Agency (EPA) § 163.81-5 "Primary dermal irritation study". Federal Register, Vol. 43, No. 163, August 22, 1978.

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin
- Weight at study initiation: 2-3 Kg
- Housing: single
- Diet (e.g. ad libitum): standard rabbit food - NAFAG, No. 814, Gossau SG
- Water (e.g. ad libitum): tap water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±2
- Humidity (%): 55±10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: abraded and intact

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

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

Duration of treatment / exposure:

24 h

Observation period:

7 days

Number of animals:

6 (3 males and 3 females)

Details on study design:

TEST SITE
- Before treatment the flanks of the rabbits were shaved with an electric clipper and immediately before treatment the shaven skin on one side was slightly scarified.
- Area of exposure: Gauze patches of 2.5 x2.5 cm with 0.5 g of the test material were applied to the prepared abraded and intact skin.

Irritation parameter:

erythema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 rabbits

Time point:

other: 24-48-72 h

Score:

0.56

Max. score:

4

Reversibility:

fully reversible within: 4 days

Irritation parameter:

edema score

Remarks:

intact skin

Basis:

mean

Remarks:

6 rabbits

Time point:

other: 24-48-72 h

Score:

0.11

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

erythema score

Remarks:

abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

other: 24-48-72 h

Score:

0.94

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Remarks:

abraded skin

Basis:

mean

Remarks:

6 rabbits

Time point:

other: 24-48-72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation score (intact skin)

Time period	Erythema						Edema
	1	2	3	4	5	6	1	2	3	4	5	6
24 h	0	2	1	0	2	1	0	1	0	0	1	0
48 h	0	1	0	0	1	0	0	0	0	0	0	0
72 h	0	1	0	0	1	0	0	0	0	0	0	0
4 d	0	0	0	0	0	0	0	0	0	0	0	0
7 d	0	0	0	0	0	0	0	0	0	0	0	0
24-72 h	0.0	1.33	0.33	0.0	1.33	0.33	0.0	0.33	0.0	0.0	0.33	0.0
Total Mean	0.56						0.11

 

Irritation score (abraded skin)

Time period	Erythema						Edema
	1	2	3	4	5	6	1	2	3	4	5	6
24 h	0	2	2	0	2	2	0	0	0	0	1	0
48 h	0	2	1	0	2	1	0	1	0	0	1	0
72 h	0	0	1	0	2	0	0	0	0	0	1	0
4 d	0	0	0	0	1	0	0	0	0	0	1	0
7 d	0	0	0	0	0	0	0	0	0	0	0	0
24-72 h	0.0	1.33	1.33	0.0	2.0	1.0	0.0	0.33	0.0	0.0	1.0	0.0
Total Mean	0.94						0.22

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present experiment the test article was found to cause no irritation when applied to intact and abraded rabbit skin.

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:

experimental study

Adequacy of study:

key study

Study period:

February 22,1982 - March 1,1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline, without GLP and only 7 day observation period

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

incomplete post observation period

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin
- Weight at study initiation: 2-3 Kg
- Housing: single
- Diet (e.g. ad libitum): standard diet, Nafag No.890
- Water (e.g. ad libitum): tap water
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 55±5
- Humidity (%): 22±2
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

not specified

Controls:

other: untreated eye of the same animal

Amount / concentration applied:

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

Duration of treatment / exposure:

30 seconds

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 (washed eye group)
3 (unwashed eye group)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, eyes of 3 rabbits flushed with 10 ml of physiological saline; eyes of 3 rabbits were kept unwashed
- Time after start of exposure: 30 s (3 rabbits)

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

6 rabbits (not-rinsed and rinsed)

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Remarks:

6 rabbits (not-rinsed and rinsed)

Time point:

other: 24-48-72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 rabbits (not-rinsed)

Time point:

other: 24-48-72 h

Score:

0.67

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: see free text for individual scores

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

3 rabbits (rinsed)

Time point:

other: 24-48-72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 rabbits (not-rinsed)

Time point:

other: 24-48-72 h

Score:

0.22

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 rabbits (rinsed)

Time point:

other: 24-48-72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Animal No.	Parameter	Score at
		24 h	48 h	72 h	4 days	7 days	24-72 h
1 Not-rinsed	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjunctivae	1	0	0	0	0	0.33
	Chemosis	0	0	0	0	0	0
2 Not-rinsed	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjunctivae	2	1	1	1	0	1.33
	Chemosis	1	0	1	1	0	0.67
3 Not-rinsed	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjunctivae	0	0	1	1	1	0.33
	Chemosis	0	0	0	0	0	0
1 Rinsed	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjunctivae	0	0	0	0	0	0
	Chemosis	0	0	0	0	0	0
2 Rinsed	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjunctivae	0	1	0	0	0	0.33
	Chemosis	0	0	0	0	0	0
3 Rinsed	Cornea	0	0	0	0	0	0
	Iris	0	0	0	0	0	0
	Conjunctivae	2	0	0	0	0	0.67
	Chemosis	0	0	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of this experiment the test material was found to cause minimal irritation when applied to the rabbit eye mucosa below the level of significance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The key study for skin irritation (CIBA-GEIGY, 1982) was performed similar to OECD guideline 404, but with occlusive coverage and 24 h exposure to intact and abraded skin of six rabbits. Transient slight erythema was developed in 4 rabbits (Draize score = 0.33-1.33) and transient slight edema was developed in 2 rabbits (Draize score = 0.33). Edema and erythema healed within seven days after exposure.

All skin reactions subsided within 48 hours after exposure during an acute dermal study (CIBA-GEIGY, 1962).

The key study for eye irritation was performed similar to OECD guideline 405 (CIBA-GEIGY, 1982) using a procedure in which after treatment, eyes of three rabbits were flushed with 10 ml of physiological saline and eyes of 3 rabbits were kept unwashed. All animals were observed for 7 days instead of 14 days. In non-rinsed animals, transient chemosis and conjunctivae redness occurred in the first animal, the second animal was without findings and in the third animal, slight redness appeared 72 h after application and was observed at the 4 and 7 day reading. For animals with rinsed eyes, slight transient conjunctivae findings were observed in one animal. Similar results were observed in another study (CIBA-GEIGY, 1962) where the test article was prepared by grinding 100 mg of the test substance with 0.3 - 0.5 milliliters of PEG 300, and instilling the mixture into one eye of each of six rabbits and observed for 48 hours. Chemosis was reversible within 48 h, but conjunctivae redness was still observed at the 48h reading.

No experimental data is available regarding respiratory irritation. In the acute inhalation study in rats, no gross pathological changes in lung were observed (CIBA-GEIGY Limited, 1973)

Justification for selection of skin irritation / corrosion endpoint:
most recent study report

Justification for selection of eye irritation endpoint:
most recent study report

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. The transient effects on skin do not meet the criteria for classification as a skin irritant. The effects on eyes were mild and mostly transient within seven days. The findings do not meet the criteria as an eye irritant. As a result the substance is not considered to be classified for skin and eye irritation under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008.

The transient effects on skin do not meet the criteria for classification as a skin irritant. The effects on eyes were mild and mostly transient within seven days. The findings do not meet the criteria as an eye irritant. As a result the substance is not considered to be classified for skin and eye irritation under Regulation (EC) No. 1272/2008.