Veratrole

Skin irritation / corrosion

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(version 1992-07-17)

Deviations:

yes

Remarks:

Only insignificant deviations from protocol

Test guideline 2

Qualifier:

according to guideline

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

Test material information

Constituent 1

Reference substance name:

Veratrole

EC Number:

202-045-3

EC Name:

Veratrole

Cas Number:

91-16-7

Molecular formula:

C8H10O2

IUPAC Name:

1,2-dimethoxybenzene

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 or test system 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

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 6 to 11 days depending on animals.

Remarks on result:

other: Mean individual score at 24, 48, 72h = 1.0/1.0/0.0

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 11 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 6 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable.

Results 5

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: Mean individual score at 24, 48, 72h =0.0/0.0/0.0

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 7

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable.

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable.

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:

GHS criteria not met

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), 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).