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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:
28-31 August 2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP study conducted in compliance with OECD Guideline 404 with minor deviations: temperature and relative humidity recorded were sometimes outside of the target ranges; systemic effects not followed; individual animal weights not reported

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
dated 17 July 1992
Deviations:
yes
Remarks:
temperature and relative humidity recorded were sometimes outside of the target ranges; systemic effects not followed; individual animal weights not reported
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
dated 31 July 1992
Deviations:
yes
Remarks:
temperature and relative humidity recorded were sometimes outside of the target ranges; systemic effects not followed; individual animal weights not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: flakes
Remarks:
whitish flakes
Details on test material:
- Expiration date of the lot/batch: 18 November 2001
- Purity test date: 27 January 2000
- Storage condition of test material: At room temperature protected from light and humidity; in its original packaging
- pH at the concentration of 10% in purified water: 7
Specific details on test material used for the study:
Date of receipt: 14 August 2001
Name as cited in the report: AMITROLE

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CEGAV, Saint Mars d'Egrenne, France
- Weight at study initiation: 2.6 ± 0.1 kg
- Housing: Animals were housed individually in polystyrene cages.
- Diet (e.g. ad libitum): 110 pelleted diet (UAR, Villemoisson, Epinay-sur-Orge, France), ad libitum
- Water (e.g. ad libitum): Drinking water filtered by a FG Millipore membrane (0.22 micron), ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3°C
- Relative humidity: 30-70%
- Photoperiod: 12 hours/12 hours
- Air changes: Approximately 12 cycles/hour of filtered, non-recycled air

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated skin served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3 male rabbits
Details on study design:
TEST SITE
- Area of exposure: Flanks
- Type of wrap if used: Test item in its original form was placed on a moistened gauze pad, which was then applied to the right flank of the animals for 4 hours. The test item and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 4 hours
- After removal of the dressing, any residual test item was wiped off by means of a dry gauze pad.

OBSERVATION TIME POINTS
- 1 hour, 24, 48 and 72 hours

SCORING SYSTEM:
- Scoring system: According to OECD Guideline 404
- Method of calculation: All scores obtained at each reading time (24, 48 and 72 hours) for an effect were used for calculating the respective mean values.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
mean individual score
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
A very slight erythema was noted in all animals on Day 1; it persisted up to Day 2 in one animal and up to Day 3 in another one. No other cutaneous reactions were observed.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1 : Individual skin reactions

Rabbits No.

1

2

3

Erythema

1 h

1

1

1

24 h

1

0

1

48 h

1

0

0

72 h

0

0

0

Mean (24, 48 and 72 hours)

0.7

0

0.3

Oedema

1 h

0

0

0

24 h

0

0

0

48 h

0

0

0

72 h

0

0

0

Mean (24, 48 and 72 hours)

0

0

0

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions and in accordance with Regulation EC No. 1272/2008 (CLP), the test item was considered as non-irritant to skin. It corresponds to UN GHS No Category. No hazard statement or signal word is required.
Executive summary:

In a primary dermal irritation study performed according to OECD Guideline 404 and in compliance with GLP, a single dose of 500 mg of the test item in its original form was applied under semi-occlusive dressing for 4 hours to the closely-clipped skin of one flank of three male New Zealand White rabbits. After removal of the dressing, cutaneous reactions were scored as outlined in the OECD Guideline 404 at 1, 24, 48 and 72 hours.

A very slight erythema was noted in all animals on Day 1; it persisted up to Day 2 in one animal and up to Day 3 in another one. No other cutaneous reactions were observed. Mean scores over 24, 48 and 72 hours for each animal were 0.7, 0.0 and 0.3 for erythema and 0.0, 0.0 and 0.0 for oedema.

Under the test conditions and in accordance with Regulation EC No. 1272/2008 (CLP), the test item was considered as non-irritant to skin. It corresponds to UN GHS No Category. No hazard statement or signal word is required.