2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone

Endpoint summary

Description of key information

- Skin irritation (OECD 404): not irritating

- Eye irritation (OECD 405): not irritating

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:

17-20 Oct 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.4

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

Adopted 28 Jul 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Good Laboratory Practice, The United Kingdom Compliance Programme, Department of Health & Social Security 1986 and subsequent revision, Department of Health 1989.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., Margate, Kent, UK
- Age at study initiation: 13-15 wks
- Weight at study initiation: 3.0-3.5 kg (range)
- Housing: individually, in plastic cages with perforated floors
- Diet: SDS Stanrab (P) rabbit diet, ad libitum
- Water: drinking water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ~19
- Humidity (%): 30-70
- Air changes (per hr): ~19
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 17 Oct 1995 To: 20 Oct 1995

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

intact

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g
- Concentration: neat, as Sponsor supplied

Duration of treatment / exposure:

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

Observation period:

Day 1 approximately 60 min after removal of the dressings, 24, 48 and 72 h after exposure ended.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: test substance was applied on the dorso-lumbar region under a 25 mm x 25 mm gauze pad moistened with 0.5 mL of distilled water.
- % coverage: not specified.
- Type of wrap if used: Elastoplast elastic adhesive dressing.

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water (30 to 40°C)
- Time after start of exposure: 4 h

OBSERVATION TIME POINTS
- Day 1 approximately 60 min after removal of the dressings, then 24, 48 and 72 h after exposure to test substance ended.

SCORING SYSTEM:
- Method of calculation: numerical system ranking scores for both oedema and erythema at each evaluation (similar to Draize evaluation).

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

No numerical response to treatment was observed in any animal at any time throughout the observation period. The individual and mean erythema score at 24/48/72 h was 0.0 in 3 of 3 animals. The individual and mean edema score at 24/48/72 h was 0.0 in 3 of 3 animals.

Interpretation of results:

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

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:

23 Oct-01 Nov 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Annex to Directive 92/69/EEC (OJ No. L383A, 29.12.92), Part B, Method B.5.

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

Adopted 24 Feb 1987

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Good Laboratory Practice, The United Kingdom Compliance, Programme, Department of Health & Social Security 1986 and subsequent revision, Department of Health 1989.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Ltd., Margate, Kent, UK
- Age at study initiation: 13-15 weeks old
- Weight at study initiation: 2.9-3.4 kg (range)
- Housing: individually, in plastic cages with perforated floors
- Diet: SDS Stanrab (P) rabbit diet, ad libitum
- Water: drinking water, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ~19
- Humidity (%): 30-70
- Air changes (per hr): ~19
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 23 Oct 1995 To: 01 Nov 1995

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 66.6 mg or 0.1 mL
- Concentration: neat, as Sponsor supplied

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

7 days
Reading time points: 1, 24, 48, 72, 96 h and 7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: single exposure without washing
- Time after start of exposure: 1, 24, 48, 72, 96 h and 7 days after instillation.

SCORING SYSTEM:
Ocular irritation was assessed using a numerical system (based on the Draize system of grading) that evaluated and produced a numerical grade for: corneal opacity (degree of density), iris (appearance and reaction to light), conjunctivae (redness and blood vessels appearance), and chemosis (swelling of eye lids and nictitating membranes).

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 rabbits

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Remarks:

at 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

At initial instillation there was transient mild conjunctival reaction scores:
1 for chemosis (any swelling [including nictitating membranes] above normal); and 1 for redness (some blood vessels definitely hyperaemic / injected) in 3 of 3 animals.
Conjunctival redness (score of 1) was recorded at 24 h in 1 rabbit only; and was fully reversible within 48 h.
Corneal opacity and iritis were recorded with scores of 0.0 at all reading time points of 1, 24, 48, 72 h and 4 and 7 days after instillation, in 3 of 3 animals.

Interpretation of results:

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

The skin irritancy potential of2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone (CAS 903-19-5)in New Zealand White rabbits was investigated under GLP conditions and according to OECD guideline 404 (Key, 1996). In this study, 0.5 g of the test substance was applied on the dorso-lumbar region of the rabbits under a gauze pad moistened with 0.5 mL of distilled water for 4 h under semiocclusive conditions. After 4 h, the semiocclusive dressing and the gauze pad was removed and the treatment site was washed with warm water. The mean erythema and edema score of all animals (24/48/72 h) was 0 for all reading time points as no numerical response to treatment was observed in any animal at any time throughout the observation period. Based on the results of this study, the test substance is not considered to have an irritancy potential towards the skin.

 

Eye irritation

In an in vivo eye irritation study with2,5-bis(1,1,3,3-tetramethylbutyl)hydroquinone (CAS 903-19-5)performed under GLP conditions and according to OECD guideline 405, 66.6 mg test substance (the weight occupying a volume of 0.1 mL) was instilled into the eye of each of 3 New Zealand White rabbits without washing (Key, 1996). The respective untreated eye served as control. The eyes were examined and graded for ocular reaction at 1, 24, 48, 72, 96 h and 7 days following instillation of test material into the eyes. The instillation of the test material resulted in a mean cornea opacity score, a mean iris score and a mean chemosis score for all animals (24/48/72 h) of 0. The mean score (24/48/72 h) for conjunctivae was 0.33, 0 and 0, 0 as conjunctival redness (score 1) was recorded in 1/3 animals 24 h after instillation of the test substance. The observed conjunctivae was fully reversible within 48 h. No conjunctival redness was shown for the other two animals. Based on the results of the conducted study, the undiluted test material did not show irritant potential towards the eyes.

Justification for classification or non-classification

The available data on skin irritation / corrosion do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.

The available data on eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.