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Description of key information

Vanillin is not irritating to the skin, and irritating to the eyes, with reversibility within 8 days.

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:
14-JUN-1991 to 13-NOV-1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was GLP
Qualifier:
according to guideline
Guideline:
other: EU Method B.3 (Acute toxicity (dermal))
Deviations:
yes
Remarks:
variation of humidity beyond the norms
GLP compliance:
yes
Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Sex: male/female
- Source: Iffa-Crédo (L'Arbresle, France)
- Age at study initiation: 5 - 8 weeks old
- Weight at study initiation: 204 - 271 g
- Fasting period before study:
- Housing: housed individually in polycarbonate cages (305 x 180 x 184 mm)
- Diet: complete pelleted rat-mouse maintenance diet, ad libitum
- Water: softened and filered mains drinking water, ad libitum
- Acclimation period: 7 days before the start of treatment

ENVIRONMENTAL CONDITIONS:
- Temperature: 20 - 24 °C
- Humidity: 43 - 85 %
- Air changes: at least 8 per hr
- Photoperiod: 12 hrs dark / 12 hrs light (artificial)

In-life dates: from 26-AUG-1991 to 09-SEP-1991
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
- Test material:
* Amount applied: 2000 mg/kg
* Concentration: 69.56 % (w/v)
* pH: 4.7
- Vehicle:
* Amount applied: data not available
* Purity: purified water
Duration of treatment / exposure:
24 hour(s)
Observation period:
14 days
Number of animals:
10
Details on study design:
- Test site:
* Area of exposure: data not available
* % coverage: approximately 10 %
* Type of wrap if used: perforrated adhesive band 10 cm wide, applied onto an elastic crepe bandage covering the entire shaved area

- Removal of test substance:
* Washing: yes, with lukewarm water
* Time after start of exposure: 24 hours

- Scoring system: according to EU guideline
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: Not applicable
Remarks on result:
other: yellowish coloration
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: yellowish coloration
Irritant / corrosive response data:
The only effect noted was a yellowish colouration of the skin of all rats on days 2 to 15 of the study. No erythema or edema were noted during the observation period.
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
GHS EU classification: not classified.
Executive summary:

In an acute dermal toxicity study (Lheritier, 1991), young adult Sprague-Dawley rats (5/sex) were dermally exposed to 2000 mg/kg bw of Cristallised Vanilline (purity unknown) in water for 24 hours to 10% body surface area. Test sites were covered with a semi-occlusive dressing for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method of EU guideline.
 
In this study, Cristallised Vanilline is not a dermal irritant based on the absence of skin reaction. Only a yellowish colour was observed from days 2 to 14.

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 11-DEC-2006 to 04-jul-2007
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 (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Grimaud frères selection SAS, La Corbière, Roussay, France
- Age at study initiation: 3 to 4 months old
- Weight at study initiation: 3 +/- 0.15 kg
- Housing : individually in Pajon cages (50*57*75 cm)
- Diet : free access to 110C pelleted diet (SAFE, Villemoisson, Epinay-sur-Orge, France
- Water : ad libidum (drinking water filtered by a FG Millipore membrane (0.22 micron))
- 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): 12 cycles per hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES : from 09 jan 2007 to 19 jan 2007
Vehicle:
unchanged (no vehicle)
Controls:
other: the other eye served as control
Amount / concentration applied:
100 mg
Observation period (in vivo):
8 days
Number of animals or in vitro replicates:
3
Details on study design:
- Washing: not rinsed
- Scoring system: OECD and EU guidelines
- Tool used to assess score: fluorescein
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 8 days
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
2
Reversibility:
fully reversible within: 4 days
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 8 days
Irritant / corrosive response data:
A slight or moderate chemosis and a slight to severe redness of the conjunctiva were observed in all animals from day 1 until day 7.
A clear to whitish purulent discharge were noted in all animals from day 1 until day 3 (2 animals) or 4 (1 animal).
An iritis was noted in all animals between day 1 and day 3.
A slight or moderate corneal opacity, which covered the whole area of the cornea of 2/3 animals on day 2, was recorded in all animals from day 2
until day 4, 5 or 6.

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

1/0/0

3/2/2

2/2/2

24 h

2/2/2

/1/1

2/2/2

1/2/2

48 h

2/2/2

1/1/0

2/2/2

1/2/2

72 h

2/2/2

0/0/0

2/2/2

1/1/2

Average 24h, 48h, 72h

2/2/2

0.7/0.7/0.3

2/2/2

1/1.7/2

Reversibility*)

c

c

c

c

Average time (unit) for reversion

(8 days)

(8 days)

(8 days)

(8 days)

 

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

Interpretation of results:
Category 2A (irritating to eyes) based on GHS criteria
Conclusions:
- Interpretation of results: Category 2A (irritating to eyes)
- Criteria used for interpretation of results: EU GHS

SUMMARY:
In a primary eye irritation study (CIT, 2007) 100 mg of Vanilline (pure product) was instilled into the conjunctival sac of right eye of a young adult New Zealand White rabbit (3 males) Animals then were observed for 8 days (period of reversibility). Irritation was scored according to the OECD and EU guidelines.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 1.7 and 2.0 for chemosis, 2.0, 2.0 and 2.0 for redness of the conjunctiva, 0.7, 0.7 and 0.3 for iris lesions and 2.0, 2.0 and 2.0 for corneal opacity.
In this study, Vanilline is irritating to the eye based on the EU classification criteria.

Classification: irritating
Executive summary:

In a primary eye irritation study (CIT, 2007) 100 mg of Vanilline (pure product) was instilled into the conjunctival sac of right eye of a young adult New Zealand White rabbit (3 males). Animals then were observed for 8 days (period of reversibility).  Irritation was scored according to the OECD and EU guidelines.


 


Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 1.7 and 2.0 for chemosis, 2.0, 2.0 and 2.0 for redness of the conjunctiva, 0.7, 0.7 and 0.3 for iris lesions and 2.0, 2.0 and 2.0 for corneal opacity.


In tis study, Vanillin is irritating to the eye based on EU classification criteria.


 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

Skin irritation:


Concerning Vanillin which composition is described in chapter 1, three studies were available. One of them performed on rat was selected as key study (Hazleton 1991, validity 1), and another one performed on rabbit (Birck 1976, validity 2) as supporting study. The third one tested on guinea pig (Makaruk 1980, validity 3) was not taken into account for assessment because the original reference was in Russian language.


The two selected studies gave the same results:not irritating to the skin. Summaries of these studies are the following:


In an acute dermal toxicity study (Hazleton, 1991), young adult Sprague-Dawley rats (5/sex) were dermally exposed to 2000 mg/kg bw of Vanilline Cristallisée (purity unknown) in water for 24 hours to 10% body surface area. Test sites were covered with a semi-occlusive dressing for 24 hours. Animals then were observed for 14 days. Irritation was scored by the method of EU guideline. In this study, cristallised Vanillin is not a dermal irritant based on the absence of skin reaction. Only a yellowish colour was observed from day 2 to 14.


In a primary dermal irritation study (Birck, 1976),New Zealandwhite rabbits (6 animals) were dermally exposed to 0.5 g of vanillin (purity unknown) for 24 hours. In this study, vanillin was not a dermal irritant.


 


Eye irritation:


Three studies performed on rabbit were available on Vanillin which composition was described in chapter 1. One of them was selected as key study (CIT 2007, validity 1), and another one (Birck 1976, validity 2) as supporting study. The third one (Makaruk 1980, validity 3) was not taken into account for assessment because the original reference is in Russian language.


The two in vivo selected studies gave the same result: irritating to the eyes. Summaries of these studies are the following:


In a primary eye irritation study (CIT, 2007) 100 mg of Vanillin (pure product) was instilled into the conjunctivae sac of right eye of a young adult New Zealand White rabbit (3 males). Animals then were observed for 8 days (period of reversibility). Irritation was scored according to the OECD and EU guidelines. Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 1.7 and 2.0 for chemosis, 2.0, 2.0 and 2.0 for redness of the conjunctiva, 0.7, 0.7 and 0.3 for iris lesions and 2.0, 2.0 and 2.0 for corneal opacity. In this study, Vanillin is irritating to the eye.


 In a primary eye irritation study [Birck, 1976], 0.1 mL of vanillin (purity unknown) undiluted was instilled into the conjunctivae sac of New Zealand White rabbits (6 animals) for 24 hours. Animals then were observed for 7 days. Irritation was scored by the method of Kay and Calandra, and in this study, vanillin is an eye irritant.


 



According to classification criteria of EC regulation 1272/2008 Vanillin was not classified as irritant for the skin and should be classified as irritant for the eyes (Eye. Irrit. Category 2, H319).



 

Justification for classification or non-classification