2,6-di-tert-butyl-α-dimethylamino-p-cresol

Endpoint summary

Description of key information

Skin irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.
No skin irritation was observed. 
Eye irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.
According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.

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:

December 4, 1984 - December 7, 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Remarks:

(Ciba-Geigy Limited, Experimental Toxicology GU 2.1, 4332 Stein/Switzerland)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Haedorin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2-3 kg
- Housing: individually in metal cages
- Diet: ad libitum standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: December 4, 1984 - December 7, 1984

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

other: the patches were moistened with water

Controls:

other: The contralateral flank treated with a control gauze patch served as control.

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

3 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: flank
- Type of wrap if used: gauze patch covered with an occlusive membrane and held in place by an adhesive tape.

SCORING SYSTEM: according to the grading scheme given in OECD guideline 404

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0.1

Reversibility:

fully reversible within: 24 hours (2/3 animals), 48 hours (1/3 animals)

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 h

Score:

0

Irritant / corrosive response data:

Minimal formation of erythema was observed in all three animals (score = 1), reversible within 48 hours the latest. All scores for edema were zero at all time points.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the experimental conditions employed the test substance induced erythema reactions below the regulatory threshold of significance, therefore, the test article is considered to be not irritating.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Test procedure in accordance with generally accepted scientific standards. Similar to OECD guideline 405. Non-GLP study.

Qualifier:

equivalent or similar to guideline

Guideline:

other: Draize JH et al. J. Exp. Pharmacol. Ther., 83, 377-390, 1944. Draize JH Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, 36-45, Ass. of Food and Drug Officials of the United States, Topeka, Kansas, 1965

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: no data reported
- Age at study initiation: no data reported
- Weight at study initiation: no data reported
- Housing: no data reported
- Diet (e.g. ad libitum): no data reported
- Water (e.g. ad libitum): no data reported

ENVIRONMENTAL CONDITIONS: no data reported

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of finely powdered AN-703 instilled onto one eye.

Observation period (in vivo):

Observation were made at 24, 48, 72 and 168 hours after application

Number of animals or in vitro replicates:

6 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE: No removal of the test substance

SCORING SYSTEM: Draize score system used to report result in the report. Raw data of the observations were available in the report, therefore, EU scoring has been reported in the results section for Cornea - Opacity, Iris - Inflammation, Conjunctivae - Redness and Chemosis.

TOOL USED TO ASSESS SCORE: Not reported in the report.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks:

(after 168 hours - score: 1)

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

1.66

Max. score:

2

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritation parameter:

iris score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

0

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

1.66

Max. score:

2

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

other: 24, 48 and 72 hours

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

other: 24, 48 and 72 hours

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 168 hours

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

other: 24, 48 and 72 hours

Score:

0.66

Max. score:

1

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Conjunctiva Chemosis score:
* Animal 1 - 24, 48 and 72 hours - 1.66 max: - 2 - fully reversible within: 168 hours
* Animal 2 - 24, 48 and 72 hours - 0
* Animal 3 - 24, 48 and 72 hours - 1 max: 2 - fully reversible within: 72 hours
* Animal 4 - 24, 48 and 72 hours - 1 max: 2 - fully reversible within: 72 hours
* Animal 5 - 24, 48 and 72 hours - 2 max: 3 - fully reversible within: 168 hours
* Animal 6 - 24, 48 and 72 hours - 0

Interpretation of results:

Category II

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.

Executive summary:

0.1 ml of the test item was applied into the conjunctival sac of one eye in each of 6 New Zealand white rabbits. The eye reactions were scored after 24, 48, 72 and 168 h. All effects were fully reversible within the observation period with the exeption of corneal opacity in one animal that however showed signs of reversibility. Mild irritation effects were observed at grades that are borderline for classification. According to the ECHA guidance on application of CLP criteria, 2009 a classification as category 2 eye irritant (H319) is proposed based on the fact that 4 of 6 rabbits had cornea scores at or above 1 for the 24, 48, 72 h average. Based on Dir. 67/548/EEC however, no classification as eye irritant (R36) would be attributed.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

No skin irritation was observed.

 

Eye irritation: Key study: Experimental result: Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.

Justification for selection of skin irritation / corrosion endpoint:
Klimisch 1. Study performed according to OECD guideline 404 (1981) and under Good Laboratory Practice.

Justification for selection of eye irritation endpoint:
Klimisch 2. Similar to OECD guideline 405. Non-GLP study.

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the available data, the substance is classified as an eye irritant:

Skin irritation: No skin irritation was observed.

Eye irritation: According the study performed the test item is considered as irritant to New Zealand white Rabbits with full reversibility after 168 hours. The test item needs to be classified as eye irritation- category 2 according to the criteria defined in the ECHA guidance on the application of CLP criteria, 2009 (249-250) CLP regulation N°1272/2008. This is based on a score of 1 or greater for cornea opacity in 4 or more of 6 animals. According to the criteria of Directive 67/548/EEC and amendments the test item is not classified as irritant to eyes.