A mixture of branched and linear C7-C9 alkyl 3-[3-(2H-benzotriazol-2-yl)-5-(1,1-dimethylethyl)-4-hydroxyphenyl]propionates

Endpoint summary

Description of key information

Skin: not irritating, OECD Guideline Study, Ciba-Geigy, 1991
Eye: not irritating, OECD Guideline Study, Ciba-Geigy, 1990

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:

August 21, 1990 - August 24, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

occlusive

GLP compliance:

yes

Remarks:

Experimental Toxicology CIBA-GEIGY Limited 4332 Stein / Switzerland

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Age at study initiation: approx. 9 - 13 weeks
- Weight at study initiation: 2580 to 2720 g
- Housing: individually in metal cages
- Diet: standard pellet, Nafag No. 814 e.g. ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Control gauze patches moistened with distilled water were applied to the contralateral flanks.

Amount / concentration applied:

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

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 mL water
- Concentration (if solution): 100%

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, 72 hours

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: right flank
- Type of wrap if used: gauze patch covered loosley with aluminum foil and held in place by an adhesive tape

SCORING SYSTEM: OECD scoring system

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.2

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: minimal reactions at the 1 hour mark in one animal

Irritant / corrosive response data:

The test substance induced minimal erythema and edema reactions revesible within 48 hours.

Individual Irritation Scores:

		Erythema	Edema
1 h	728	1	0
	723	1	0
	706	1	1
24 h	728	1	0
	723	0	0
	706	1	0
48 h	728	0	0
	723	0	0
	706	0	0
72 h	728	0	0
	723	0	0
	706	0	0
mean 24 - 72 h	728	0.3	0.0
	723	0.0	0.0
	706	0.3	0.0
mean 24 - 72 h		0.2	0.0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test article caused minimal dermal reactions below the threshold of significance and is therefore regarded as not irritating to the rabbit skin.

Executive summary:

In an acute dermal irritation/corrosion study following OECD guideline 404 and in compliance with GLP, three New Zealand White rabbits were exposed to 0.5 ml of the test substance. A gauze patch (approx.12-16 cm) bearing the test article was applied to the right flank of each animal. A control gauze patch was applied to the contralateral flank. Both patches were moistened before application with test material. The patches were loosely covered with an aluminum foil (approx. 36 cm²) and held in place for 4 hours by an adhesive tape. The animals were checked daily for systemic symptoms and mortality. The skin reactions were evaluated 1, 24, 48, and 72 hours after removing the gauze patches according to the OECD scoring system. Under the experimental conditions employed the test substance induced mild erythema and edema reactions revesible within 48 hours when applied to the clipped albino rabbit skin. Because the mean values of the recordings 24 to 72 hours after application are below the threshold of significance, the test article is considered as not irritating to the 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:

August 28, 1990 - September 7, 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-compliant guideline study (OECD)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

GLP compliance:

yes

Remarks:

Experimental Toxicology CIBA-GEIGY Limited 4332 Stein / Switzerland

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Chemisch-pharmazeutische Fabrik, D-7950 Biberach/Riss
- Age at study initiation: approx. 9 - 13 weeks
- Weight at study initiation: 2290 to 2560 g
- Housing: individually in metal cages
- Diet: standard rabbit pellet - Nafag No. 814, Gossau, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±3
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as a control

Amount / concentration applied:

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

Duration of treatment / exposure:

single instillation, not washed

Observation period (in vivo):

1, 24, 48, 72 hours and 10 days

Number of animals or in vitro replicates:

3 males

Details on study design:

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

SCORING SYSTEM: OECD scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 10 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritant / corrosive response data:

Instillation of the test substance caused minimal corneal irritation in 2/3 animals at the 1-hour timepoint, reversible within 24 hours. Conjunctival effects were redness and chemosis in all three animals; chemosis was reversible after 24 hours and redness after 10 days.

Other effects:

No other effects.

Individual Irriation Scores:

				Conjunctiva
		Cornea	Iris	Redness	Chemosis
1 h	245	1	0	2	1
	799	1	0	2	1
	895	0	0	2	1
24 h	245	0	0	1	0
	799	0	0	1	0
	895	0	0	1	0
48 h	245	0	0	1	0
	799	0	0	1	0
	895	0	0	1	0
72 h	245	0	0	1	0
	799	0	0	1	0
	895	0	0	1	0
mean 24 - 72 h	245	0.0	0.0	1.0	0.0
	799	0.0	0.0	1.0	0.0
	895	0.0	0.0	1.0	0.0
mean 24 - 72 h		0.0	0.0	1.0	0.0
7 days	245	0	0	0	0
	799	0	0	1	0
	895	0	0	1	0
10 days	245	0	0	0	0
	799	0	0	0	0
	895	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions employed the test article induced mild irritation of the cornea and conjunctiva below the threshold of signifcance and is therefore regarded as not irritating to the rabbit eye.

Executive summary:

In a GLP-compliant eye irritation study performed according to OECD guideline 405, three New Zealand White rabbits were treated with 0.1 ml of the test article. The test article was placed into the conjunctival sac of the left eye of each animal; the lids were then held together for about one second in order to prevent loss of the test material. The right eye remained untreated and served as a control. The ocular reactions were evaluated 1, 24, 48, and 72 hours after instillation and animals were checked daily for signs of systemic toxicity. Because reactions were observed within 72 hours after instillation of the test article, the observation period was extended to 10 days. Instillation of the test substance caused minimal corneal irritation in 2/3 animals at the 1-hour time point, reversible within 24 hours. Conjunctival effects were redness and chemosis in all three animals; chemosis was reversible after 24 hours and redness after 10 days. Since the observed ocular effects were below the threshold of significance, the test article is classified as not irritating.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin: In a GLP-compliant primary dermal irritation study (OECD 404, Ciba-Geigy, 904254), 3 female New Zealand White rabbits were dermally exposed to 0.5 mL of the test substance for 4 hours under occlusive conditions. Animals were then observed for 3 days. Irritation was scored by the method of Draize as described in the OECD guideline 404. Minimal dermal reactions were recorded below the threshold of significance. The mean score for the 24, 48 and 72 h reading for erythema was 0.2 and for edema was 0. The skin reactions observed were reversible within 48 days. Based on the results of this study, the test article is regarded as not irritating to the rabbit skin.

Eye: A GLP-compliant eye irritation test was performed with three male New Zealand White rabbits according to OECD 405 (Ciba-Geigy, 904253). Eyes were left unwashed after application of 0.1 mL of test material and the animals were observed 10 days. The mean scores for the 24, 48 and 72 h readings for iritis, cornea opacity and conjunctivae chemosis were 0 at any of this reading time points. For conjunctivae redness the mean score for the 24, 48 and 72 h reading was 1. The eye reactions observed were reversible until the end of the observation period on day 10. In this study, the test substance is not an eye irritant.

Respiratory system: No data available.

Justification for selection of skin irritation / corrosion endpoint:
GLP-compliant guideline study

Justification for selection of eye irritation endpoint:
GLP-compliant guideline study

Justification for classification or non-classification

Skin & Eye

Dangerous Substance Directive (67/548/EEC): The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for skin and eye irritation under Directive 67/548/EEC.

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. As a result the substance is not considered to be classified for skin and eye irritation under Regulation (EC) No. 1272/2008.

Respiratory system

At present, there are no data available for this endpoint.