(3-methoxy-2-methylpropyl)benzene

Endpoint summary

Description of key information

Skin irritation: Not irritating (OECD 404, GLP, Rel.1, K).
Eye irritation: Not irritating (OECD 405, GLP, Rel. 1, K).

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:

key study

Study period:

From August 04 to 13, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Storage condition of test material: Stored at room temperature, away from the light and heat.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: BERTHO, 22120 Yffiniac, France
- Weight at study initiation: 2.3 kg (average weight)
- Housing: Animals were housed individually on floor grids.
- Diet: Complete pelleted rabbit maintenance diet Energie H326 (COFNA, 37000 - Tours, France)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS: Environmental conditions and controls were in accordance with the requirements of the 86/609/EEC guideline.

IN-LIFE DATES: From: August 04, 1997 To: August 13, 1997.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

Duration of treatment / exposure:

4 h

Observation period:

1, 24, 48 and 72 h after patch removal and then on Days 5, 6, 7, 8 and 9.

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Dorsal area of the trunk
- Type of wrap if used: Test material was applied to the clipped skin and covered with a gauze (2.5 x 2.5 cm) held in place by means of a 5 x 5 cm wide "Micropore" fastening tape. Then the animal's trunk was wrapped with a 10 cm wide stretch tape (varicose vein tape) fastened by adhesive tape of the same width and placed in such a way so as not to hinder respiratory movements.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test material was removed using absorbent paper moistened with distilled water.
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scale, as described in OECD Guideline 404.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 9 day

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 9 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- Formation of erythema and oedema of index 1 (in 1 animal) or index 2 (in 2 animals) were observed at 1 h after patch removal.
- At 24 h observation, 2 animals exhibited a well-defined erythema with barely visible oedema, and a very slight erythema was noted in the third animal.
- A very slight or well defined erythema was noted in the two animals and no cutaneous reaction was observed in the third animal after 48 h.
- Observed oedematous and erythematous reactions were completely disappeared within 72 h and 9 days respectively.

Other effects:

None

Table 7.3.1/1: Mean irritant/corrosive response data for each animal at each observation time up to removal of animals from the test

Score at time point	Erythema (Animal no 1 / 2 / 3) Max. score 4	Oedema (Animal no 1 / 2 / 3) Max. score 4
1 h	2 / 2 / 1	2 / 2 / 1
24 h	2 / 2 / 1	1 / 1 / 0
48 h	2 / 2 / 1	0 / 1 / 0
72 h	1 / 2 / 0	0 / 0 / 0
Day 5	1 / 2 / -	0 / 0 / -
Day 6	1 / 2 / -	0 / 0 / -
Day 7	1 / 2 / -	0 / 0 / -
Day 8	1 / 1 / -	0 / 0 / -
Day 9	0 / 0 / -	0 / 0 / -
Average 24, 48 and 72 h	1.7 / 2.0 / 0.7	0.3 / 0.7 / 0.0
Reversibility	Completely reversible	Completely reversible
Average time for reversion	9 days	72 h

Key:

- : No reading

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

Under the test conditions, test material is not classified as irritant to the skin according to the criteria of the Annex VI of Regulation (EC) No. 1272/2008 (CLP) but is classified as mild irritant (Category 3) according to the GHS.

Executive summary:

In a dermal irritation study performed according to the OECD Guideline No. 404, and in compliance with GLP, 0.5 mL of the test material was applied on the clipped skin of three male New Zealand White rabbits. The test material was held in contact with the skin by means of a semi-occlusive dressing for 4 h. Skin reactions were assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after removal of the dressing and on Days 5, 6, 7, 8 and 9.

Formation of erythema and oedema of score 1 (in 1 animal) or score 2 (in 2 animals) were observed at 1 h after patch removal. At 24 h observation, 2 animals exhibited a well-defined erythema with barely visible oedema, and a very slight erythema was noted in the third animal. A very slight or well defined erythema was noted in the two animals and no cutaneous reaction was observed in the third animal after 48 h. Observed oedematous and erythematous reactions had completely disappeared within 72 h and 9 days respectively.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.7 / 2.0 / 0.7 for erythema and 0.3 / 0.7 / 0.0 for oedema.

Under the test conditions, test material is not classified as irritant to the skin according to the criteria of the Annex VI of Regulation (EC) No. 1272/2008 (CLP) but is classified as mild irritant (Category 3) according to the GHS.

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

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:

key study

Study period:

From August 04 to 14, 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

- Storage condition of test material: Stored at room temperature, away from the light and heat (tox specific)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: BERTHO, 22120 Yffiniac, France
- Weight at study initiation: 2.8 kg (average weight)
- Housing: Animals were housed individually on floor grid.
- Diet: Complete pelleted rabbit maintenance diet (Energie H326, COFNA, 37000 - Tours, France)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS: Environmental conditions and controls were in accordance with the requirements of the 86/609/EEC guideline.

IN-LIFE DATES: From: August 04, 1997 To: August 14, 1997.

Vehicle:

unchanged (no vehicle)

Controls:

other: 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:

No washing was done.

Observation period (in vivo):

1, 24, 48 and 72 h after instillation and then on Days 5-11

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not done

SCORING SYSTEM: Draize scale, as described in the OECD guideline No. 405.

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

cornea opacity score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 11 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 11 days

Irritation parameter:

chemosis score

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

- At 1 h after instillation: A moderate irritation of the conjunctivae (crimson coloration, tumefaction, important discharge) was observed in all animals and a slight congestion of the iris was noted in one animal.
- At 24 h after instillation: The discharges had nearly disappeared and a conjunctival enanthema was noted in all animals with a very slight oedema in two of them. Marked redness (index 2) was observed and a diffuse area of cornea opacity was reversible within 24 h in one animal.
- At 72 h after instillation: No ocular reaction was observed in one animal. A slight palpebral irritation (enanthema of index 2 and oedema of index 1) was noted in the two other animals.
- The chemosis was reversible within 7 days and the palpebral redness disappeared 11 days after instillation.

Other effects:

None

Table 7.3.2/1: Eye irritation response data for each animal at each observation time

Score at time point	Cornea		Iris (/2)	Conjunctivae
	Opacity (/4)	Area (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
1 h (Day 1)	0 / 0 / 0	0 / 0 / 0	1 / 0 / 0	2 / 2 / 2	1 / 1 / 1	3 / 3 / 2
24 h (Day 1)	1 / 0 / 0	1 / 0 / 0	0 / 0 / 0	2 / 1 / 1	1 / 0 / 1	1 / 0 / 0
48 h (Day 2)	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	2 / 1 / 1	1 / 0 / 1	1 / 0 / 0
72 h (Day 3)	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	2 / 0 / 2	1 / 0 / 1	1 / 0 / 1
Day 5	0 / - / 0	0 / - / 0	0 / - / 0	2 / - / 2	1 / - / 1	1 / - / 1
Day 6	0 / - / 0	0 / - / 0	0 / - / 0	2 / - / 2	1 / - / 1	0 / - / 0
Day 7	0 / - / 0	0 / - / 0	0 / - / 0	2 / - / 2	0 / - / 0	0 / - / 0
Day 8	0 / - / 0	0 / - / 0	0 / - / 0	1 / - / 1	0 / - / 0	0 / - / 0
Day 9	0 / - / 0	0 / - / 0	0 / - / 0	1 / - / 1	0 / - / 0	0 / - / 0
Day 10	0 / - / 0	0 / - / 0	0 / - / 0	1 / - / 1	0 / - / 0	0 / - / 0
Day 11	0 / - / 0	0 / - / 0	0 / - / 0	0 / - / 0	0 / - / 0	0 / - / 0
Average 24, 48 and 72 h	0.3 / 0.0 / 0.0	0.3 / 0.0 / 0.0	0.0 / 0.0 / 0.0	2.0 / 0.7 / 1.3	1.0 / 0.0 / 1.0	1.0 / 0.0 / 0.3
Reversibility	Completely reversible	Completely reversible	-	Completely reversible	Completely reversible	Completely reversible
Average time (unit) for reversion	48 h	48 h	-	72 h to 11 days	24 h to 7 days	24 h to 6 days

Key:

- : No reading

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and according the GHS.

Executive summary:

In an eye irritation study performed according to the OECD Guideline No. 405, and in compliance with GLP, 0.1 mL of undiluted test material was instilled into the right eye of 3 female New Zealand White rabbits. The lids are then gently held together for about one second in order to prevent loss of the material. The left eye remained untreated and served as control. Animals were observed at 1, 24, 48 and 72 h after test material instillation, and then on Days 5-11. The reactions in the conjunctiva (redness, chemosis and discharge), the iris and the cornea (opacity and area involved) were scored according to the Draize scale.

A moderate irritation of the conjunctivae was observed in all animals and a slight congestion of the iris was noted in one animal at 1 h after instillation. 24 h after instillation, the discharges had nearly disappeared and a conjunctival enanthema was noted in all animals with a very slight oedema in two of them. Marked redness was observed and a diffuse area of cornea opacity was reversible within 24 h in one animal. No ocular reaction was observed in one animal at 72 h. A slight palpebral irritation was noted in the two other animals. The chemosis was reversible within 7 days and the palpebral redness disappeared 11 days after instillation.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.3 / 0.0 / 0.0 for cornea score; 0.0 / 0.0 / 0.0 for iris score; 2.0 / 0.7 / 1.3 for conjunctivae score and 1.0 / 0.0 / 1.0 for chemosis score.

Under the test conditions, the test material is not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.

This study is considered as acceptable and satisfies the requirement for eye irritation endpoint.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation:

A key study was identified (EVIC, 1997). This dermal irritation study was performed according to the OECD Guideline No. 404, and in compliance with GLP.

Formation of erythema and oedema of score 1 (in 1 animal) or score 2 (in 2 animals) were observed at 1 h after patch removal. At 24 h observation, 2 animals exhibited a well-defined erythema with barely visible oedema, and a very slight erythema was noted in the third animal. A very slight or well defined erythema was noted in the two animals and no cutaneous reaction was observed in the third animal after 48 h. Observed oedematous and erythematous reactions were completely disappeared within 72 h and 9 days, respectively.

The individual scores for each animal within 3 scoring times (24, 48 and 72 h) were 1.7 / 2.0 / 0.7 for erythema and 0.3 / 0.7 / 0.0 for oedema.

Under the test conditions, test material is not classified as irritant to the skin.

Eye irritation:

A key study was identified (EVIC, 1997). This eye irritation study was performed according to the OECD Guideline No. 405, and in compliance with GLP.

A moderate irritation of the conjunctivae was observed in all animals and a slight congestion of the iris was noted in one animal at 1 h after instillation. 24 h after instillation, the discharges had nearly disappeared and a conjunctival enanthema was noted in all animals with a very slight oedema in two of them. Marked redness was observed and a diffuse area of cornea opacity was reversible within 24 h in one animal. No ocular reaction was observed in one animal at 72 h. A slight palpebral irritation was noted in the two other animals. The chemosis was reversible within 7 days and the palpebral redness disappeared 11 days after instillation.

Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 0.3 / 0.0 / 0.0 for cornea score; 0.0 / 0.0 / 0.0 for iris score; 2.0 / 0.7 / 1.3 for conjunctivae score and 1.0 / 0.0 / 1.0 for chemosis score.

Under the test conditions, the test material is not classified as irritating to eyes.

Justification for selection of skin irritation / corrosion endpoint:
Only one study available. The key-study is GLP-compliant and of high quality (Klimisch score = 1).

Justification for selection of eye irritation endpoint:
Only one study available. The key-study is GLP-compliant and of high quality (Klimisch score = 1).

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Based on the available data, the substance is:

- not classified as irritant to the skin according to the criteria of the Annex VI of Regulation (EC) No. 1272/2008 (CLP)

- is classified as mild skin irritant (Category 3) according to the GHS.

No additional self-classification is proposed regarding eye irritation according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and according to the GHS.

No data was available regarding respiratory irritation. However, the substance only being a mild irritant to the skin, no classification is expected for respiratory irritation.