Registration Dossier

Administrative data

Description of key information

The test substance was assessed for skin and eye irritation.  There was potential for skin irritation, according to Regulation  67/548/EEC (DSD).  There was no potential for eye irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-11-08 to 1988-11-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well docmented and acceptable for assessment.
Qualifier:
according to
Guideline:
other: EC Directive L251 of 1984-04-25
Principles of method if other than guideline:
4 rabbits dermally exposed to 0.5 mL of test material semi-occlusively for 4 hrs, observed for 7 d
GLP compliance:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): Nonanal, CAS No. 124-19-6
- Substance type: Fragrance material
- Physical state: Liquid
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: No data
- Isomers composition: No data
- Purity test date: No data
- Lot/batch No: No data
- Expiration date of the lot/batch: No data
- Stability under test conditions: No data
- Storage condition of test material: In the dark at approx. 4 °C
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gorseside Rabbits, Northchurch, Berkhamsted, Hertfordshire, United Kingdom
- Age at study initiation: 10-12 wks
- Weight at study initiation: approx. 2 kg
- Housing: Individually in grid-bottomed metal cages
- Diet: Commercial antibiotic-free pellet diet ad libitum
- Water: Mains water ad libitum
- Acclimation period: ≥ 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 17- 23 °C typically; dropped to 5 °C temporarily during acclimation due to heating failure
- Humidity: 37 % - 68 %
- Air changes (per hr): No data
- Photoperiod: 12 hrs dark / 12 hrs light)
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Volume applied: 0.5 mL
Duration of treatment / exposure:
4 hrs
Observation period:
7 d (observations at 1 hr, 24 hrs, 48 hrs, 72 hrs, 7 d)
Number of animals:
4
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm square
- Type of wrap if used: Lint held in place with "Elastoplast" elastic adhesive bandage 10 cm wide

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Gentle swabbing with cotton wool in warm water.
- Time after start of exposure: 4 hrs

SCORING SYSTEM: Standard Draize
Irritation parameter:
erythema score
Basis:
animal: 349
Time point:
other: Mean of 24, 48, 72 hrs
Score:
2
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
edema score
Basis:
animal: 349
Time point:
other: Mean of 24, 48, 72 hrs
Score:
1.17
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
erythema score
Basis:
animal: 370
Time point:
other: Mean of 24, 48, 72 hrs
Score:
2
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
edema score
Basis:
animal: 370
Time point:
other: Mean of 24, 48, 72 hrs
Score:
1.5
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
erythema score
Basis:
animal: 374
Time point:
other: Mean of 24, 48, 72 hrs
Score:
2
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
edema score
Basis:
animal: 374
Time point:
other: Mean of 24, 48, 72 hrs
Score:
1
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
erythema score
Basis:
animal: 381
Time point:
other: Mean of 24, 48, 72 hrs
Score:
2.17
Reversibility:
not reversible
Remarks:
within 7 d
Irritation parameter:
edema score
Basis:
animal: 381
Time point:
other: Mean of 24, 48, 72 hrs
Score:
2.17
Reversibility:
not reversible
Remarks:
within 7 d
Irritant / corrosive response data:
Marked desquamation at 7 d
Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was assessed for skin irritation in rabbits following a 4 hour exposure period. The results indicate that the test material was irritating to skin as the mean erythema score was 2.0 in all 4 animals which was equal to the threshold value of 2.0 under Regulation 67/548/EEC (DSD).
Endpoint:
skin corrosion: 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:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 November 1980 to 17 November 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions
Qualifier:
according to
Guideline:
EPA OPP 81-4 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
no
Remarks:
Study predates GLP
Specific details on test material used for the study:
- Name of test material (as cited in study report): C-193; SN 2188-3; Aldehyde C9 Nonylic
- Appearance: Colourless liquid
- Storage condition of test material: Room temperature (stored under nitrogen)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Dutchland Laboratory Animals, Denver, Pennsylvania
- Age at study initiation: Young adults
- Weight at study initiation: 2.2 to 2.9 kg
- Housing: Animals were housed individually in suspended stainless steel cages
- Diet: Purine rabbit chow, available ad libitum
- Water: Automatic watering system (municipal water supply) available ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17 - 20.5 °C; monitored twice daily
- Humidity: monitored daily
- Photoperiod: 12 hours light, 12 hours dark
Vehicle:
unchanged (no vehicle)
Controls:
other: The contralateral eye served as the control.
Amount / concentration applied:
0.1 mL of the test material was introduced into the lower conjunctival sac of the right eye of each animal. The upper and lower lids were gently held together for one second prior to releasing to prevent loss of material.
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
Up to 7 days
Number of animals or in vitro replicates:
9 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
The treated and control eyes of 6 animals remained unwashed. Twenty seconds after the test substance was administered, both eyes of the remaining 3 animals were rinsed for one minute with lukewarm water.

OBSERVATIONS
-Viability checks were performed twice daily.
- Evaluations of eye irritation were performed approximately 24, 48 and 72 hours and 4 and 7 days after treatment. If there were no signs of irritation on Day 7, no additional observations were made.
- At each interval the treated and control eyes were examined and scored for ocular reactions. Unusual effects were also noted when present.

SCORING SYSTEM: Draize scale (see Appendix A in section "Attached background material")

TOOL USED TO ASSESS SCORE: Fluorescein dye
Irritation parameter:
cornea opacity score
Basis:
animal: All animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: All scores were 0
Irritation parameter:
iris score
Basis:
animal: All animals
Time point:
other: 24, 48 and 72 hours
Score:
0
Remarks on result:
other: All scores were 0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1.33
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score for redness
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1.67
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean score for redness
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean score for redness
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
2
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean score for redness
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score for redness
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1.67
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean score for redness
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
0.33
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Mean score
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: Mean of 24, 48 and 72 h scores
Score:
1
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Mean score
Irritant / corrosive response data:
All nine rabbits exhibited positive scores for conjunctival redness and five animals with unwashed eyes showed positive scores for conjunctival chemosis. Conjunctival necrosis was observed in three animals with unwashed eyes. A positive score for iridial irritation was observed in one rabbit with washed eyes. All animals were free of signs of ocular irritation within seven days after administration of the test material.

The individual scores are given in Table 1.

The results from the animals whose eyes were washed have not been included as part of the classification assessment.

Table 1: Individual ocular scores

-

Time after administration

24 hours

48 hours

72 hours

4 days

7 days

Animal No. 6408F

Conjunctivae:

-

-

-

-

-

Redness

2

2

0

1

0

Chemosis

2

1

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

0

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6409M

Conjunctivae:

-

-

-

-

-

Redness

2

2

1

0

0

Chemosis

2

1

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

N

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6410F

Conjunctivae:

-

-

-

-

-

Redness

3

2

1

0

0

Chemosis

2

1

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

0

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6411M

Conjunctivae:

-

-

-

-

-

Redness

2

2

2

0

0

Chemosis

2

1

0

0

0

Discharge

1

0

0

0

0

Necrosis (N)

N

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6412F

Conjunctivae:

-

-

-

-

-

Redness

2

1

0

0

0

Chemosis

1

0

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

0

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6415M

Conjunctivae:

-

-

-

-

-

Redness

2

2

1

0

0

Chemosis

2

1

0

0

0

Discharge

2

0

0

0

0

Necrosis (N)

N

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6414Fb

Conjunctivae:

-

-

-

-

-

Redness

2

0

0

0

0

Chemosis

0

0

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

0

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6417Mb

Conjunctivae:

-

-

-

-

-

Redness

2

1

0

0

0

Chemosis

1

0

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

0

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

0

0

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

Animal No. 6418Fb

Conjunctivae:

-

-

-

-

-

Redness

2

1

1

0

0

Chemosis

0

0

0

0

0

Discharge

0

0

0

0

0

Necrosis (N)

0

0

0

0

0

Ulceration (U)

0

0

0

0

0

Iris

1

1

0

0

0

Cornea

-

-

-

-

-

Opacity

0

0

0

0

0

Area

0

0

0

0

0

Stippling

0

0

0

0

0

Ulceration

0F

0F

0

0

0

F: Observation confirmed with fluorescein

b: Both eyes were rinsed for one minute with lukewarm water 20 seconds after dosing

Interpretation of results:
GHS criteria not met
Conclusions:
The test substance was assessed for eye irritation according to EPA OPP 81-4. The test material is not considered to be an eye irritant and is not classified according to Regulation No. 1272/2008.
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

The key study report indicated that the test material was irritating to skin as the mean erythema score was 2.0 in all 4 animals which was equal to the threshold value of 2.0 under Regulation 67/548/EEC. Within the framework of Regulation (EC) No. 1272/2008, which uses a threshold of 2.3 rather than 2.0, this result is negative.

Eye irritation

In the key study, the test substance was found not to be irritating to eyes.


Justification for selection of skin irritation / corrosion endpoint:
Key study that meets generally accepted scientific standards, well documented and acceptable for assessment.

Justification for selection of eye irritation endpoint:
Key study performed according to a guideline, with acceptable restrictions.

Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

The test substance was assessed for skin and eye irritation. There was no potential for skin irritation within the framework of Regulation (EC) No. 1272/2008 (CLP), however in accordance with Regulation 67/548/EEC the test substance is classified as a skin irritant.

There was no potential for eye irritation.