3-ethoxy-4-hydroxybenzaldehyde

Endpoint summary

Description of key information

Ethylvanillin is slightly irritating to skin, and not classified according to the CLP 1272/2008/EC classification criteria.
Ethylvanillin 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 (CLP 1272/2008/EC).

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 irrit category 2 (H319).

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

Effects on skin irritation/corrosion: slightly irritating, but not classified according to the EU classification criteria.
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 CLP 1272/2008/EC criteria.

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