Registration Dossier

Administrative data

Description of key information

1- Skin irritation: not irritating to skin (Comparable to OECD 404, Reliability 2, GLP)

2- Eye irritation: not irritating to eyes (Comparable to OECD 405, Reliability 2, GLP)

3- Respiratory irritation: no data available.

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:
10/03/02 - 10/18/02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No certificate of analysis.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
Simplied study.
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Vanillic acid
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient temperature
- Stability under test conditions: yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White rabbits (Oryctolagus cuniculus)
- Sex: males and females.
- Sources: Millbrook Breeding Labs, Amherst, MA.
- Age at study initiation: at least 10 weeks old (adult)
- Weight at study initiation: 2.05 - 2.31 kg.
- Housing: individual housing, in suspended stainless steel.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 10 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3°C
- Humidity: 30 to 70%
- Air changes: 10 TO 15
- Photoperiod: 12 hrs dark / 12 hrs light

I
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
Concentration: 0.5 g
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 (1 male and 2 females)
Details on study design:
TEST SITE
- Area of exposure: a surface of about 6 cm2
- % coverage: no data
- Type of wrap: a surgical gauze measuring 25X25 mm.


REMOVAL OF TEST SUBSTANCE
- Washing: the bandages were removed and if necessary excess test substance which had not penetrated was wiped away with a gauze pad moistened with distilled water
- Time after start of exposure: 4 hours

SCORING SYSTEM: based on erythema and oedema formation, according to directive OECD 404
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions of this study, Vanillic acid is not considered as irritating to skin and not classified according to EU criteria.
Executive summary:

In a dermal irritation study (Comparable to OECD 404, GLP), three New-Zealand White rabbits were dermally exposed to 0.5 mL of vanillic acid on a 6 cm2 body surface area. Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 3 days. Irritation was scored by the method of OECD guideline 404.

The mean scores (24, 48 and 72 hours) for both oedema and erythema were 0.0 for all animals. Under the test conditions of this study, Vanillic acid is considered as not irritating to skin and therefore not classified according to EU 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:
10/03/02 - 10/20/02
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No certificate of analysis.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
Simplified study.
GLP compliance:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Vanillic acid
- Expiration date of the lot/batch: no data
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: ambient temperature
- Stability under test conditions: yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Strain: New Zealand White rabbits (Oryctolagus cuniculus)
- Sex: males and females
- Sources: Millbrook Breeding Labs, Amherst, MA.
- Weight at study initiation: 2.04 to 2.19 kg / at least 10 weeks old (adult). Weighed to nearest 10 g.
- Housing: individual housing, in suspended stainless steel.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum 10 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3°C
- Humidity: 30 to 70%
- Air changes: 10 TO 15
- Photoperiod: 12 hrs dark / 12 hrs light
Vehicle:
other: no
Controls:
yes, concurrent no treatment
Amount / concentration applied:
Amount applied: 0.1 ml
Observation period (in vivo):
3 days
Number of animals or in vitro replicates:
3 (2 males and 1 female).
Details on study design:
REMOVAL OF TEST SUBSTANCE
no washing

SCORING SYSTEM: based on changes in cornea, iris, conjunctivae and chemosis, according to guideline OECD 405

TOOL USED TO ASSESS SCORE: Heine's ophthalmoscope / fluorescein

Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours.
Remarks on result:
other: see table of results
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.66
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable.
Remarks on result:
other: see table of results
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable.
Remarks on result:
other: see table of results
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
other: Not applicable.
Remarks on result:
other: see table of results
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: see table of results
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
ca. 0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours.
Remarks on result:
other: see table of results.

Table 1: 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

1/1/1

 0/0/0

1/2/2 

2/2/2

24 h

1/1/1

 0/0/0

 1/1/2

 1/1/1

48 h

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

Average 24h, 48h, 72h

0.33/0.33/0.33

 0/0/0

 0.33/0.33/0.66

 0.33/0.33/0.33

Reversibility*)

 n.

n. 

n. 

n. 

Average time (unit) for reversion

c

-

c

 

*) Reversibility: c. = completely reversible

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions of this study, Vanillic acid is not considered as irritating to eyes. Therefore, no classification is required according to EU criteria.
Executive summary:

In an eye irritation study (Comparable to OECD 405, Reliablity 2, GLP), 0.1 mL of Vanillic acid was instilled into the conjunctival sac of the right eye of three New-Zealand White rabbits (no rinsing). Animals were then observed for 3 days. Ocular irritation was scored by Draize method. The mean scores (24, 48 and 72 hours) are 0.33/0.33/0.33 for chemosis, 0.33/0.33/0.66 for redness, 0/0/0 for iris and 0.33/0.33/0.33 for cornea opacity. These ocular irritation signs were fully reversible after 2 days. The results indicate that the test substance has slight irritant effect in the eye of the rabbit However; no classification is required according to EU criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

1- Skin irritation:

One study was available and considered as the key study (Comparable to OECD 404, GLP). In this study, three New-Zealand White rabbits were dermally exposed to 0.5 mL of vanillic acid. Animals were then observed for 3 days.

The mean scores (24, 48 and 72 hours) for both oedema and erythema were 0.0 for all animals. Under the test conditions of this study, Vanillic acid is considered as not irritating to skin.

2- Eye irritation:

One study was available and considered as the key study (Comparable to OECD 405, GLP). In this study, 0.1 mL of Vanillic acid was instilled into the conjunctival sac of the eye of three New-Zealand White rabbits. Animals were then observed for 3 days. Ocular irritation was scored by the method of Draize. The mean scores (24, 48 and 72 hours) are 0.33/0.33/0.33 for chemosis, 0.33/0.33/0.66 for redness, 0/0/0 for iris and 0.33/0.33/0.33 for cornea opacity. These ocular irritation signs were fully reversible after 2 days. The results indicate that the test substance has slight irritant effect in the eye of the rabbit.

3- Respiratory irritation: no data available.

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008.

Self classification:

1- Skin irritation:

Based on the results of the key study (Comparable to OECD 404, GLP), Vanillic acid is not considered as irritating to skin and therefore no classification is required according to EU criteria.

2- Eye irritation:

Based on the results of the key study (Comparable to OECD 405, GLP), Vanillic acid is considered as slightly irritating to eyes but no classification is required according to EU criteria.

3- Respiratory irritation:

No classification is proposed due to lack of data.