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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:
30 December 2011 - 20 January 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Compliant to GLP and testing guidelines; adequate consistence between data, comments and conclusions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: 1,3-Diphenyl-2-thiourea
- Physical state: white powder
- Lot/batch No.: 1012001047
- Analytical purity: 94.2%
- Expiry date: 12 January 2013
- Storage conditions: protected from moisture and heat, at room temperature.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: breeder: Charles River Laboratories France, l’Arbresle, France
- Age at study initiation: 5 months old on the day of treatment
- Mean body weight at study initiation: a mean body weight of 3850 g (3740 g to 3984 g)
- Fasting period before study: no
- Housing: noryl cages
- Diet: 110 pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

IN-LIFE DATES: 10 January 2012 to 20 January 2012.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied: A dosage-volume of 500 mg/flank was used.
Duration of treatment / exposure:
3 minutes, 1 hour, 4 hours.
Observation period:
1, 24, 48 and 72 h after removal of the dressing; if relevant, daily until reversibility of reactions
Number of animals:
3 females.
Details on study design:
TEST SITE
- Area of exposure: During each exposure time, a dry gauze pad was applied to the opposite flank, in order to check that no alteration of the skin is induced by the semi-occlusive dressing and restraining bandage.
The untreated flank acted as control.
- Coverage: 6 cm2
- Type of wrap if used: gauze pad held in place by a non-irritation semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: using a dry cotton pad
- Time after start of exposure: at removal of each dressing (see Duration of exposure)

SCORING SYSTEM:

- 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)

- Edema formation:
0 no edema
1 very slight edema (barely perceptible)
2 slight edema (edges of area well-defined by definite raising)
3 moderate edema (raised approximately 1 millimeter)
4 severe edema (raised more than 1 millimeter 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
Remarks:
3 rabbits
Time point:
other: 24, 48, 72 h (mean)
Score:
0.7
Max. score:
4
Remarks on result:
other: Individual scores = 0.7 - 0.3 - 0.3
Irritation parameter:
edema score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24, 48, 72 h (mean)
Score:
0
Max. score:
4
Remarks on result:
other: All individual scores = 0
Irritant / corrosive response data:
After 3-minute and 1-hour exposures (animal 101), a very slight erythema (grade 1) was noted from day 1 up to day 3.
After a 4-hour exposure (three animals), a very slight erythema (grade 1) was noted in all animals from day 1 up to day 2 (animals 102 and 103) or 3 (animal 101).
Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:
. erythema: 0.7, 0.3, 0.3; showing no significant inflammation,
. edema: 0.0, 0.0, 0.0; showing no significant inflammation.
Other effects:
No unscheduled deaths occurred during the study. No clinical signs were noted in any animals.
The body weight of the animals was unaffected by the test item treatment.

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC 1272/2008
Conclusions:
The test item was slightly irritant when applied topically to rabbits.
However, the test item is not classified as irritating to skin according to the criteria of CLP Regulation.
Executive summary:

The objective of this study was to evaluate the potential corrosive and irritant properties of the test item following dermal application on rabbits.

 

Methods

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single female New Zealand White rabbit.

After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal is < 2.3 for erythema and for edema, the test item was applied on the skin of two other animals for 4 hours.

A dosage-volume of 500 mg/flank was used.

The test item was placed on a gauze pad, moistened with drinking water treated by reverses osmosis, which was then applied to a skin area of approximately 6 cm2. The gauze pad was held in place by a non‑irritation semi-occlusive dressing and a restraining bandage. After required period of contact with the skin, the dressing was removed.

Each animal was observed once a day for mortality and clinical signs. For each exposure period, cutaneous reactions were evaluated 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 edema were calculated for each animal. Body weight was recorded at the beginning and the end of the observation period.

On completion of the observation period, the animals were used subsequently for the evaluation of the ocular irritation potential of the same test item.

 

Results

No unscheduled deaths occurred and no clinical signs were noted during the study.The body weight of the animals was unaffected.

 

After 3-minute and 1-hour exposures (one animal), a very slight erythema was noted from day 1 to day 3.

 

After a 4-hour exposure (three animals), a very slight erythema was noted from day 1 to day 2 (2/3 animals) or 3 (1/3 animals).

 

Mean scores calculated for each animal over 24, 48 and 72 hours were as follows:

.            erythema: 0.7, 0.3, 0.3; showing no significant inflammation,

.            edema: 0.0, 0.0; 0.0; showing no significant inflammation.

 

Conclusion

The test item was slightly irritant when applied topically to rabbits.

However, the test item is not classified as irritating to skin according to the criteria of CLP Regulation.