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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2002

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Butylal
- Physical state: Colourless liquid
- Analytical purity: > 99.99%
- Impurities (identity and concentrations): Formaldehyde (0.0038% w/w), water (not detected), n butanol (not detected).
- Composition of test material, percentage of components: Formaldehyde (0.0038% w/w), water (not detected), n butanol (not detected), butylal (>99.99% w/w)
- Lot/batch No.: E971205
- Expiration date of the lot/batch: No expiry date
- Storage condition of test material: at room temperature and protected from light

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle, 80160 Prouzel, France
- Age at study initiation: not specified
- Weight at study initiation: the animals had a mean body weight of 2.4 ± 0.1 kg.
- Housing: The animals were housed individually in polystyrene cages (35 cm x 55 cm x 32 cm or 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): During the study, the animals had free access to 112 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France). Each batch of food was analysed by the supplier for composition and contaminant levels.
- Water (e.g. ad libitum): Drinking water filtered by a F.G. Millipore membrane (0.22 micron) was provided ad libitum. Bacteriological and chemical analysis of the water and diet, including the detection of possible contaminants (pesticides, heavy metals and nitrosamines), are performed regularly by external
laboratories. No contaminants are known to be present in the diet or drinking water at levels which may be expected to interfere with or prejudice the outcome of the study.
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3
- Humidity (%): 30 to 70
The temperature and relative humidity were under continuous control and recording. The records were checked daily and retained. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals.
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air.
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: not specified

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): undiluted

VEHICLE
The test substance was used undiluted.
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: The day before treatment, the flanks of each animal were clipped using electric clippers and the skin of each animal was examined. Only animals with healthy intact skin were used.
- % coverage: not specified
- Type of wrap if used: A single dose of 0.5 ml of the test substance was placed on a 6 cm2 dry gauze pad (Coopérative Pharmaceutique Française, 77000 Melun, France), which was then applied to the right flank of the animals for 4 hours.
The test substance and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing (Laboratoires de Pansements et d'Hygiène, 21300 Chenove, France) and a restraining bandage (Coheban), Laboratoires 3M Santé, 92245 Malakoff, France).

REMOVAL OF TEST SUBSTANCE
No residual test substance was observed on removal of the dressing.

SCORING SYSTEM:
Dermal irritation was evaluated for each animal according to the following scoring scale:

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

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

Any other lesions were noted.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24h (D2)
Score:
1.3
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48h (D3)
Score:
1
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72h (D4)
Score:
1.7
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1h (D1) and 24h (D2)
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 48h (D3) and 72h (D4)
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 96h (D5)
Score:
1
Max. score:
4
Reversibility:
fully reversible within: D6
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1h (D1) and 24h (D2)
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 48h (D3)
Score:
1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 72h (D4), 96h (D5)
Score:
2
Max. score:
4
Reversibility:
fully reversible within: D6
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1h (D1) and 24h (D2)
Score:
1
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 48h (D3), 72h (D4), 96h (D5)
Score:
2
Max. score:
4
Reversibility:
fully reversible within: D6
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24h (D2), 48h (D3) and 72h (D4)
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
animal: #1, #2 and #3
Time point:
other: D1 to D6
Score:
0
Max. score:
4
Irritant / corrosive response data:
A very slight or well-defined erythema (grade 1 or 2) was observed in all animals from day 3 to day 5 for two animals, from day 1 to day 5 for the third one.
Dryness of the skin was recorded in one animal from day 6 up to the end of the observation period (day 15).
Mean scores over 24, 48 and 72 hours for each animal were 1.3, 1.0 and 1.7 for erythema and 0.0, 0.0 and 0.0 for oedema.
Other effects:
Dryness of the skin was observed in animal #3 from day 6 to 15.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under our experimental conditions, the test substance BUTYLAL is slightly irritant when applied topically to rabbits.
According to the classification criteria laid down in Commission Directive 93/21/E.E.C., the test substance should not be classified as irritating to the skin.
Executive summary:

The potential of the test substance BUTYLAL to induce skin irritation was evaluated in rabbits according to O.E.C.D. (No. 404, 17th July 1992) and E.C. (92/69/E.E.C., B.4, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The study design was established according to available information on the test substance and the above guidelines. The test substance was applied for 4 hours to three male New Zealand White rabbits. A single dose of 0.5 ml of the undiluted test substance was applied to the closely-clipped skin of one flank. The test substance 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 the end of the observation period. The mean values of the scores for erythema and oedema were calculated for each animal. The interpretation of results was carried out according to the classification criteria laid down in Commission Directive 93/21/E.E.C. (27th April 1993) adapting to technical progress for the eighteenth time Council Directive 67/548/E.E.C.

A very slight or well-defined erythema was observed, from day 3 to day 5 in two animals, from day 1 to day 5 in the third one. Dryness of the skin was recorded in one animal from day 6 up to the end of the observation period (day 15). Mean scores over 24, 48 and 72 hours for each animal were 1.3, 1.0 and 1.7 for erythema and 0.0, 0.0 and 0.0 for oedema.

Under our experimental conditions, the test substance BUTYLAL is slightly irritant when applied topically to rabbits. According to the classification criteria laid down in Commission Directive 93/21/E.E.C., the test substance should not be classified as irritating to the skin.