Registration Dossier

Administrative data

Description of key information

Ethylvanillin is slightly irritating to skin, and not classified according to the Directive 67/548/EC and the CLP 1272/2008/EC classification criteria.
Ethyl vanillin is not an eye irritant to the eye based on the 67/548/EC directive classification criteria, but it is classified eye irritant category 2 (H319), according to the CLP 1272/2008/EC classification criteria.

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:
From may 2003 to 28 august 2003
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 2.4 +/- 0.2 kg
- Housing: individually in polystyrene cages (48.2*58*36.5 cm)
- Diet (e.g. ad libitum): free access to 110 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a Millipore membrane (0.22 micron), ad libitum.
- Acclimation period: at least 5 days before the start of the study.

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

IN-LIFE DATES: From: 27 may 2003 To: 30 may 2003
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: control on the other untreated flank
Amount / concentration applied:
500 mg
Duration of treatment / exposure:
4 hour(s)
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: on one flank
- Type of wrap if used: the test item 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): any residual test item was miped off by means of a moistened cotton pad.

SCORING SYSTEM: according to the Commission Directive 2004/73/EC
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Other effects:
yellow coloration of the skin

Irritant/corrosive response data for each animal at each observation time up to removal of each animal from the test:

Score at time point / Reversibility

Erythema

Edema

Max. score: 4

Max. score: 2

 60 min

1/1/0

0/0/0

 24 h

1/1/0

0/0/0

 48 h

1/0/0

0/0/0

 72 h

0/0/0

0/0/0

Average 24h, 48h, 72h

0.7/0.3/0

0/0/0

Reversibility

Yes at 72 hours

/

 

Interpretation of results:
GHS criteria not met
Conclusions:
Not irritating.

Executive summary:

In one primary dermal irritation study of validity 1 (Klein, 2003), young adult New Zealand White rabbits (3 males) were dermally exposed to 500 mg of ethylvanillin onto one flank. Test sites were covered with semi-occlusive dressing for 4 hours. Animals then were observed for 72 hours.

Irritation was scored by the method of the Commission Directive 2004/73/EC. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.3 and 0 for erythema and 0, 0 and 0 for edema. 

In this study, ethylvanillin is very slightly irritant when applied topically to rabbits, but not classified according to the EU classification criteria.

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:
From may 2003 to 05 sept 2003
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
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Age at study initiation: 2 to 4 months old
- Weight at study initiation: 3 +/- 0.4 kg
- Housing: individually in polystyrene cages (48.2*58*36.5 cm)
- Diet (e.g. ad libitum): free access to 110 pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France).
- Water (e.g. ad libitum): drinking water filtered by a Millipore membrane (0.22 micron), ad libitum.
- Acclimation period: at least 5 days before the start of the study.


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


IN-LIFE DATES: From: 03 jun 2003 To: 17 jun 2003
Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE: not rinsed
SCORING SYSTEM: according to the Commission Directive 2004/73/EC
TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 5 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 5 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #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:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.3
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.3
Max. score:
4
Reversibility:
fully reversible within: 6 days

Eye irritant/corrosive response data for each animal at each observation time:

Score at time point / Reversibility

Cornea

Iris

Conjunctivae

Chemosis

Max. score: 4

Max. score: 2

Max. score: 3

Max. score: 4

60 min

0/0/0

0/0/0

2/3/3

3/3/3

24 h

2/1/1

1/0/0

3/2/2

3/2/3

48 h

2/1/1

1/0/0

3/1/1

2/1/1

72 h

0/1/0

1/0/0

2/0/1

2/1/0

Average 24h, 48h, 72h

1.3/1/0.7

1/0/0

2.7/1/1.3

2.3/1.3/1.3

Reversibility*)

c

c

c

c

Average time (unit) for reversion

5 days

5 days

7 days

6 days

 

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

 

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Classified irritating according to CLP regulation.


Executive summary:

In one primary eye irritation study of validity 1 (Klein, 2003), 100 mg of ethylvanillin was instilled into the conjunctival sac of left eye of young adult New Zealand White rabbits (3 animals). Eyes were not rinsed and the right eye served as control. Animals then were observed for 7 days.

Irritation was scored by the method according to the Commission Directive 2004/73/EC. Mean scores calculated for each animal over 24, 48 and 72 hours were 2.3, 1.3 and 1.3 for chemosis, 2.7, 1 and 1.3 for redness of the conjunctivae, 1, 0 and 0 for iris lesions and 1.3, 1 and 0.7 for corneal opacity.

In this study, ethylvanillin was slightly eye irritant and based on the EU classification criteria (1272/2008) it should be classified as Eye irri. category 2 (H319).

It is not classified according to the 67/548/EC directive criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:

Only one study was available with the reliability 1 according to Klimish, and was selected as key study.

In this primary dermal irritation study (CIT, 2003), young adult New Zealand White rabbits (3 males) were dermally exposed to 500 mg of ethylvanillin onto one flank.

Test sites were covered with semi-occlusive dressing for 4 hours. Animals then were observed for 72 hours. Irritation was scored by the method of the Commission Directive 2004/73/EC.

Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.3 and 0 for erythema and 0, 0 and 0 for edema.

In this study, ethylvanillin is very slightly irritant when applied topically to rabbits, but not classified according to the EU classification criteria.

 

Eye irritation:

Two studies were available with reliability 1 according to Klimish. One in vitro study and one in vivo study. The in vivo study was selected as key study.

In this key study, a primary eye irritation study (CIT, 2003), 100 mg of ethylvanillin was instilled into the conjunctival sac of left eye of young adult New Zealand White rabbits (3 animals). Eyes were not rinsed and the right eye served as control. Animals then were observed for 7 days. Irritation was scored by the method according to the Commission Directive 2004/73/EC.

Mean scores calculated for each animal over 24, 48 and 72 hours were 2.3, 1.3 and 1.3 for chemosis, 2.7, 1 and 1.3 for redness of the conjunctivae, 1, 0 and 0 for iris lesions ans 1.3, 1 and 0.7 for corneal opacity.

In this study, Ethyl vanillin is not an eye irritant to the eye based on the 67/548/EC directive classification criteria.

It is classified eye irritant category 2 (H319), according to the CLP 1272/2008/EC classification criteria.


Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the results obtained in the studies, Ethylvanillin is:

- Not clasified for skin irritation according to the directive 67/548/EC and CLP 1272/2008 criteria.

- Not classified for eye irritation according to the directive 67/548/EC criteria.

- Classified Eye irritation Cat. 2 (H319) according to CLP 1272/2008/EC criteria.