Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003-11-12 to 2003-11-23
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Only insignificant deviations from protocol (Temperature and relative humidity were occationally outside the specified ranges.) GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004
Report Date:
2004

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(version 1992-07-17)
Deviations:
yes
Remarks:
Only insignificant deviations from protocol
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(version 1992-07-31)
Deviations:
yes
Remarks:
Only slight deviations from protocol
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): vératrole

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France.
- Age at study initiation: 2 to 4 months
- Weight at study initiation: mean body weight ± standard deviation of 3.5 ± 0.1 kg.
- Housing: individual housing in polystyrene cages (48.2 cm x 58 cm x 36.5 cm). Each cage was equipped with a food container and a water bottle.
- 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 FG Millipore membrane (0.22 micron) was provided ad libitum.
- Acclimation period: at least 5 days before the beginning of the study.
- sex; male


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


IN-LIFE DATES: From: 2003-11-12 To: 2003-11-23

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated skin site served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted
Duration of treatment / exposure:
One animal: 3 minutes on one flank and 4 hours on the other flank
Two other animals: 4 hours on one flank
Observation period:
1, 24, 48, 72 hours and 11 days after removal of dressing
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: no data
- % coverage: no data
- Type of wrap if used: gauze pad; held in contact with the skin by means of an adhesive hypoallergic aerated semi-occlusive dressing and a restraining bandage


REMOVAL OF TEST SUBSTANCE
- Washing (if done): no, wiped off with dry cotton pad
- Time after start of exposure: 4 hours (or 3 minutes - one animal)


SCORING SYSTEM
Erythema and eschar formation
- no erythema: 0
- very slight erythema (barely perceptible): 1
- well-defined erythema: 2
- moderate to severe erythema: 3
- severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

Oedema formation
- no oedema: 0
- very slight oedema (barely perceptible): 1
- slight oedema (edges of area well- defined by definite raising): 2
- moderate oedema (raised approxunately 1 millimetre): 3
- severe oedema (raised more than 1 millimetre and extending beyond area of exposure): 4

Any other lesions were noted.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Remarks:
following 4h exposure
Basis:
mean
Time point:
other: overall 24, 48 and 72 hours
Score:
0 - 1
Max. score:
4
Reversibility:
fully reversible within: 6 to 11 days
Remarks on result:
other: Mean individual score at 24, 48, 72h = 1.0/1.0/0.0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: overall 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Remarks on result:
other: Mean individual score at 24, 48, 72h =0.0/0.0/0.0
Irritant / corrosive response data:
After a 3-minute exposure (animal #276 - pretest): No cutaneous reactions were observed.
After a 4-hour exposure (three animals): 2/3 animals showed very slight erythema (score 1 of max 4) on days 2-4. One of these animals showed very slight erythema for 10 days (animal number 276). The other animal showed very slight erythema for 6 days (animal number 281). The third animal showed no erythema (animal number 282).
None of the three animals showed edema formation at any time.
Other effects:
Dryness of the skin was seen in animal number 276 on day 6.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the experimental conditions, the test item Veratrole is slightly irritant when applied topically to rabbits. However, according to the classification criteria laid down in Regulation (EC) 1272/2008 (CLP) and in Council Directive 67/548/EEC (and subsequent adaptations), the test item should not be classified as irritating to the skin.
Executive summary:

The potential of the test item Veratrole to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 17th July 1992) and EC (92/69/EEC, B.4, 31st July 1992) guidelines.

In the first instance, the test item was applied for periods of 3 minutes and 4 hours to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then applied for 4 hours to two other animals.

A single dose of 0.5 mL of the undiluted test item was applied to the closely-clipped skin of one flank. The test item was held in contact with the skin by means of a semi-occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until reversibility of cutaneous reactions.

The mean values of the scores for erythema and oedema were calculated for each animal.

A very slight erythema was noted in 2/3 animals from day 1 up to day 10 or from day 2 up to day 5. No other cutaneous reactions were recorded during the study. Mean individual scores over 24, 48 and 72 hours for each animal were 1.0, 1.0 and 0.0 for erythema and 0.0, 0.0 and 0.0 for oedema.

Under these experimental conditions, the test item Veratrole is slightly irritant when applied topically to rabbits.

In these conditions, Veratrole is not classified according to the Regulatio (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.