Reaction mass of 3-(3,3-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-5-yl)propanal and 3-(1,1-dimethyl-2,3-dihydro-1H-inden-4-yl)propanal

Endpoint summary

Description of key information

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

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:

October 1999

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Taking effects as from 13th May 1998, until 29th January 2000

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: not reported
- Weight at study initiation: on the day of treatment, the animals had a mean body weight ± standard deviation of 2.5 ±0.3 kg.
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet (e.g. ad libitum): free access to 112 C pelleted diet (UAR, 91360 Villemoissonsur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external laboratories.
No contaminants were known to have been present in the diet or drinicing water at levels which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1999-10-06 To: 1999-10-13

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of one flank.

Duration of treatment / exposure:

4 hours

Observation period:

Examinations were done approximately 1 hour, 24, 48 and 72 hours after removal of the dressing, then daily up to reversibility (Day 8)

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: right flank
- Type of wrap if used: A single dose of 0.5 mL of the undiluted test substance was placed on a dry gauze pad, which was then applied to the right flank of the animals for 4 hours. The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not needed

SCORING SYSTEM:
Erythema and eschar formation:
0: - No erythema
1: - Very slight erythema (barely perceptible)
2: - Well defined erythema
3: - Moderate to severe erythema
4: - Severe erythema (beet redness) to slight eschar formation (injuries in depth)
Oedema formation:
0: - No oedema
1: - Very slight oedema (barely perceptible)
2: - Slight oedema (edges of area well defined by definite raising)
3: - Moderate oedema (raised approximately 1 mm)
4: - Severe oedema (raised more than 1 mm and extending beyond area of exposure)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 120 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 96 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

A well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was observed on days 5, 6 and 7 in animal#1. See Table 7.3.1/1.

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 / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	2 / 2 / 2	0 / 0 / 0
24 h	1 / 1 / 1	0 / 0 / 0
48 h	1 / 1 / 1	0 / 0 / 0
72 h	1 / 0 / 1	0 / 0 / 0
Average 24h, 48h, 72h	1.0 / 0.67 / 1.0	0.0 / 0.0 / 0.0
Reversibility*)	c.	-
Average time for reversion	120 hours	-

 

  *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material induces a slight to well-defined erythema being reversible within 6 days. Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of 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 undiluted test material was applied on the clipped skin of the right flank of 3 males New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 hours after the removal of the patch and up to reversibility.

A well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was recorded in one animal between day 5 and 7.

The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 1.00 / 0.67 / 1.00 for erythema and 0.00 / 0.00 / 0.00 for oedema.

Therefore the test material is not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

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

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[further information is included as attachment to Iuclid section 13]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physico-chemical, toxicological and environmental fate properties because of their composition similarity

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target and the source substances are reaction mass, composed of three and two dimethylindanylpropanal isomers, respectively.

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is not a skin irritant in the available study. The study design (OECD 404, GLP) is adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
The absence of skin irritation of the target substance is also supported by the acute dermal toxicity study in which no sign of irritation was observed in rats at 2000 mg/kg bw.
Therefore, based on the considerations above, it can be concluded that the results of the skin irritation studies conducted in the rabbit with the source substance are likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirement of Annex VII, 8.1

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 120 hours

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 96 hours

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

A well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was observed on days 5, 6 and 7 in animal#1. See Table 7.3.1/1.

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 / Reversibility	Erythema Max. score 4	Oedema Max. score 4
1 h	2 / 2 / 2	0 / 0 / 0
24 h	1 / 1 / 1	0 / 0 / 0
48 h	1 / 1 / 1	0 / 0 / 0
72 h	1 / 0 / 1	0 / 0 / 0
Average 24h, 48h, 72h	1.0 / 0.67 / 1.0	0.0 / 0.0 / 0.0
Reversibility*)	c.	-
Average time for reversion	120 hours	-

 

  *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the source substance induces a slight to well-defined erythema being reversible within 6 days. Therefore the target and source substances are not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of 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 undiluted source substance was applied on the clipped skin of the right flank of 3 males New Zealand White rabbits. Test sites were covered with a semi-occlusive dressing for 4 hours. Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48, 72 hours after the removal of the patch and up to reversibility.

A well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was recorded in one animal between day 5 and 7.

The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 1.00 / 0.67 / 1.00 for erythema and 0.00 / 0.00 / 0.00 for oedema for the source substance.

Therefore the source and target substances are not classified as irritant to the skin according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

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

Reference 3

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:

October 1999

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

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

not applicable

GLP compliance:

yes (incl. QA statement)

Remarks:

Taking effects as from 13th May 1998, until 29th January 2000

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France.
- Age at study initiation: not reported
- Weight at study initiation: on the day of treatment, the animals had a mean body weight ± standard deviation of 2.6 ±0.4 kg.
- Housing: individually in polystyrene cages (48.2 cm x 58 cm x 36.5 cm).
- Diet (e.g. ad libitum): free access to 112 C pelleted diet (UAR, 91360 Villemoissonsur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a FG Millipore membrane (0.22 micron) was provided ad libitum.
Bacteriological and chemical analyses of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external laboratories.
No contaminants were known to have been present in the diet or drinicing water at levels which may be expected to have interfered with or prejudiced the outcome of the study.
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: From: 1999-10-13 To: 1999-10-16

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
0.1 mL of the undiluted test substance was instilled into the conjuntival sac of the left eye of three rabbits.

Duration of treatment / exposure:

single exposure (the eyes were not rinsed after administration of the test item)

Observation period (in vivo):

The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration.

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

SCORING SYSTEM:
CONJUCTIVAE
Chemosis (A) : lids and/or nictitating membranes
0: - No swelling
1: - Any swelling above normal (includes nictitating membranes)
2: - Obvious swelling with partial eversion of lids
3: - Swelling with lids about half closed
4: - Swelling with lids more than half closed
Discharge (B) :
0: - No discharge
1: - slight discharge (does not include small amounts normally found in inner canthus)
2: - Discharge with moistening of the lids and hairs just adjacent
3: - Discharge with moistening of the lids and considerable area around the eye
Redness (C) : refers to palpebral and bulbar conjunctivae, cornea and iris
0: - Blood vessels normal
1: - Some blood vessels definitely hyperaemic (injected)
2: - Diffuse, crimson colour, individual vessels not easily discernible
3: - Diffuse beefy red
IRIS (D)
0: -Normal
1: - Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2: - No reaction to light, haemorrhage, gross destruction (any or all of these)
CORNEA
Opacity (E) : degree of density (area most dense are taken for reading)
0: - No ulceration or opacity
1: - Scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible
2: - Easily discernible translucent area, details of iris slightly obscured
3: - Nacreous area, no details of iris visible, size of pupil barely discernible
4: - Opaque cornea, iris not discernible through the opacity
Area of cornea involved (F)
1: - One-quarter (or less) but not zero
2: - Greater than one-quarter-less than one-half.
3: - Greater than one-half-less than three quarters
4: - Greater than three-quarters-up to whole area

Any other lesions observed were noted.

TOOL USED TO ASSESS SCORE: fluorescein (batch No. 9812), at 24h only.

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Only very slight or slight (grade 1 or 2) conjunctival reactions (very slight or slight chemosis and very slight redness of the conjunctiva) were observed in all animals on day 1; they persisted for 24 hours in two animals. No other ocular reactions were observed during the study. See Table 7.3.2/1.

Other effects:

none

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility	Cornea	Iris (/2)	Conjunctivae
	Opacity (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
1 h	0 / 0 / 0	0 / 0 / 0	1 / 1 / 1	1 / 2 / 2	E
24 h	0 / 0 / 0	0 / 0 / 0	0 / 1 / 1	0 / 0 / 1	0 / 0 / 0
48 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Average 24h, 48h, 72h	0 / 0 / 0	0 / 0 / 0	0.0 / 0.33 / 0.33	0.0 / 0.0 / 0.33	0 / 0 / 0
Reversibility*)	-	-	c.	c.	-
Average time for reversion	-	-	48 h	48 h	-

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 E = scoring masked by residual test substance

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material induced very slight to slight irritation being reversible within 48 hours. Therefore the test material is not classified as irritant to the eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

Executive summary:

In an eye irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.1 mL of test material was instilled into the left eye of 3 male New Zealand White rabbits. The eyes were not rinsed after the instillation of the test material. The right eye of each rabbit served as control. Animals were observed at 1 hour, 24, 48 and 72 hours after dosing. No further observation was performed since complete reversibility was achieved within 48 hours. 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.

The individual score for each animal within 3 scoring times (24, 48 and 72 hours) were as follows: 0.0 / 0.33 / 0.33 for redness, 0.0 / 0.0 / 0.33 for chemosis.

No other ocular reactions were observed during the study.

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 of the GHS.

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

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
[further information is included as attachment to Iuclid section 13]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physico-chemical, toxicological and environmental fate properties because of their composition similarity

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target and the source substances are reaction mass, composed of three and two dimethylindanylpropanal isomers, respectively.

3. ANALOGUE APPROACH JUSTIFICATION
The source substance is not an eye irritant in the available study. The study design (OECD 405, GLP) is adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
Therefore, based on the considerations above, it can be concluded that the results of the eye irritation studies conducted in the rabbit with the source substance are likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirement of Annex VII, 8.2.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal: #2 and #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal: #1 and #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Only very slight or slight (grade 1 or 2) conjunctival reactions (very slight or slight chemosis and very slight redness of the conjunctiva) were observed in all animals on day 1; they persisted for 24 hours in two animals. No other ocular reactions were observed during the study. See Table 7.3.2/1.

Other effects:

none

Table 7.3.2/1: Irritant/corrosive response data each animals at each observation time up to removal from the test

 

Score at time point / Reversibility	Cornea	Iris (/2)	Conjunctivae
	Opacity (/4)		Redness (/3)	Chemosis (/4)	Discharge (/3)
1 h	0 / 0 / 0	0 / 0 / 0	1 / 1 / 1	1 / 2 / 2	E
24 h	0 / 0 / 0	0 / 0 / 0	0 / 1 / 1	0 / 0 / 1	0 / 0 / 0
48 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
72 h	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0	0 / 0 / 0
Average 24h, 48h, 72h	0 / 0 / 0	0 / 0 / 0	0.0 / 0.33 / 0.33	0.0 / 0.0 / 0.33	0 / 0 / 0
Reversibility*)	-	-	c.	c.	-
Average time for reversion	-	-	48 h	48 h	-

*) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

 E = scoring masked by residual test substance

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the source substance induced very slight to slight irritation being reversible within 48 hours. Therefore the source and target substances are not classified as irritant to the eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

Executive summary:

In an eye irritation study performed according to the OECD guideline No. 404, and in compliance with GLP, 0.1 mL of source substance was instilled into the left eye of 3 male New Zealand White rabbits. The eyes were not rinsed after the instillation of the test material. The right eye of each rabbit served as control. Animals were observed at 1 hour, 24, 48 and 72 hours after dosing. No further observation was performed since complete reversibility was achieved within 48 hours. 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.

The individual score for each animal within 3 scoring times (24, 48 and 72 hours) were as follows: 0.0 / 0.33 / 0.33 for redness, 0.0 / 0.0 / 0.33 for chemosis for the source substance.

No other ocular reactions were observed during the study.

Therefore, the source and target substances are not classified as irritating to eyes according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and of the GHS.

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

Reference 3

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:

No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purpose as data relates to a mixture of dimethylindanylpropanal isomers, which is also the case for the registered substance.

In the dermal irritation study performed on the supporting substance according to the OECD guideline No. 404 and in compliance with GLP (CIT, 2000), a well-defined erythema (grade 2) was noted in all animals on day 1, then a very slight erythema (grade 1) was observed up to day 3, 4, or 5. Dryness of the skin was recorded in one animal between day 5 and 7. The individual scores for each animal within 3 scoring times (24, 48 and 72 hours) were 1.00 / 0.67 / 1.00 for erythema and 0.00 / 0.00 / 0.00 for oedema. Under the test conditions, the supporting substance is not a skin irritant.

Eye irritation :

No study was available on the substance itself, therefore a read-across approach was used. The supporting substance is considered adequate for read-across purpose.

In the eye irritation study performed on the supporting substance according to the OECD guideline No. 404 and in compliance with GLP (CIT, 2000), the individual score for each animal within 3 scoring times (24, 48 and 72 hours) were as follows: 0.0 / 0.33 / 0.33 for redness, 0.0 / 0.0 / 0.33 for chemosis. No other ocular reactions were observed during the study. Under the test conditions, the supporting substance is not an eye irritant.

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

No data was available regarding respiratory irritation. However, the substance not being classified for skin and eye irritation, no classification is expected for respiratory irritation .