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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
Study period:
17th to 26th July 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in accordance with recognised guideline. Although no data is available on the study's GLP compliance equivalent quality assurance methods were in place at the testing laboratory. The substance is present in an oil formulation at ca. 30%.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Remarks:
Quality assurance audit and study director statements included in the report

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
Dinoseb (DNBP) in oil 300 g/l.
30-31.2% w/w DNBP.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Morton Commercial Rabbits, Stansted, Essex
- Age at study initiation: approximately 9 to 11 weeks of age
- Weight at study initiation: 2.1 to 2.5 kg
- Housing: the rabbits were individually housed in metal cages with perforated floors
- Diet/water (e.g. ad libitum): free access to tap water and SDS Standard Rabbit Diet
- Acclimation period: the rabbits selected for the study were all acclimated to the laboratory environment

ENVIRONMENTAL CONDITIONS
- Temperature (°C): approximately 19°C
- Humidity (%): 30-70%
- Air changes (per hr): Air exchange was maintained at approximately 19 air changes per hour
- Photoperiod (hrs dark / hrs light): lighting was controlled by means of a time switch to give 12 hours of artificial light (0700-1900 hours) in each 24 hour period.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml of 30-31.2% w/w DNBP dosed as received
Duration of treatment / exposure:
4 hours
Observation period:
Examination of the treated skin was made on Day 1 (i.e. approximately 30 minutes after removal of the patches) and on Days 2, 3 and 4. Additional observations were made on Days 5 through 10.
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 10 cm square.
A 0.5 ml aliquot of DNBP formulation was applied under a 2.5 cm square gauze pad to one intact skin site on each animal.
- Type of wrap if used: each treatment site was occluded with "Elastoplast" elastic adhesive dressing for a four hour period. The animals were not restrained during the exposure period and were returned to their cages.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure period, the semi-occlusive dressing and gauze pad were removed and the treatment site was washed using distilled water to remove any residual test substance.
- Time after start of exposure: 4 hours

SCORING SYSTEM:
Grading and scoring of the dermal reactions were performed using the prescribed numerical scoring system as follows:

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 the area of exposure)

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
1.7
Max. score:
4
Reversibility:
fully reversible within: 10 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 9 days
Irritant / corrosive response data:
Well-defined erythema with very slight oedema was observed in all three animals on Day 2. These reactions gradually ameliorated and by Days 9 and 10 the skins were normal.
Assessment of erythema on Day 1 was precluded, due to staining of the skin by the test substance.
There were no other lesions.

Any other information on results incl. tables

A single occluded application of DNBP formulation to intact rabbit skin for four hours elicited well-defined dermal irritation.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A single occluded application of DNBP formulation to intact rabbit skin for four hours elicited well-defined dermal irritation.
The mean values of the scores for erythema and oedema formation at 24, 48 and 72 hours were calculated as 1.9 and 1 respectively and therefore the substance does not need to be classified as irritating according to the dangerous substances directive, 67/548/EEC.
Executive summary:

The primary dermal irritation potential of the test material was evaluated in rabbits under 4-hour semi-occluded conditions.

A single occluded application of DNBP formulation to intact rabbit skin for four hours elicited well-defined dermal irritation.

The mean values of the scores for erythema and oedema formation at 24, 48 and 72 hours were calculated as 1.9 and 1 respectively and therefore the substance does not need to be classified as irritating according to the dangerous substances directive, 67/548/EEC.