Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 24, 2013
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Remarks:
no major deviations only minor deviations that have no impact on results
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
- Diet: SDS/DIETEX STANRAB (P) SQC feed was available ad libitum.
- Water:Drinking water was available ad libitum in polycarbonate bottles with a stainless steel nipple. A specimen of water is sent approximately every 6 months to Laboratoire de la Touraine - ZA n°1 du Papillon - Rue de l0Aviation - 37210 Parçay-Meslay - France, for analysis. The criteria for acceptable levels of contaminants in the water supplied were within the limits of the analytical specifications.
-Housing: Observation was performed at the time of delivery of the animals and daily during the acclimatisation period. Animals were housed individually in cages of standard size. These cages were placed in an air-conditioned (15- 21°C) animal house kept at between 45 % and 65 % relative humidity (except during the cleaning slot) in which non-recycled filtered air is changed approximately 10-15 times per hour. These parameters are continuously recorded using a computerised acquisition system. The artificial day/night cycle was 12 hours light and 12 hours darkness with light on at 7.30 a.m.
- IN-LIFE DATES: Start of the study (signature of the study plan by the Study Director): 02 May 2013, Start of the experimental period: 06 May 2013, End of the experimental period: 16 May 2013.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 mL of "hydrate de carbone et sucres, hexitol, anhydro" LAB 4623 was applied to the skin of the right or the left flank region. The test item was applied to the selected area on the right or left flank of each animal. Adjacent surfaces of non-treated skin of each animal served as a control for the trial.
The test item was placed directly on the skin, over an area of approximately 6 cm² then covered with a non-irritating gauze square of the same surface area. This gauze square was protected by a pad consisting of a semi-occlusive micro-porous and non-allergenic dressing, held in place with a soft and aerated fastening system consisting of elastic, adhesive, hypoallergenic tape. The animals were fitted with this pad for the duration of the exposure period. At the end of the exposure period, the dressing was removed. Since the application of the test item induced a brown colouration, the application sites were rinsed using a waterlogged gauze and a control zone was also rinsed and served as control. The standard amounts applied were not adjusted to body weight.
Duration of treatment / exposure:
3 min, 1h, 4h on the skin for the first animal, 4h for the two others.
Observation period:
For the initial test in one animal, due to the colouration of the treatment sites, the application site was not examined immediately after the patch has been removed. One hour, 24 hours, 48 hours and 72 hours approximately after patch removal dermal reactions on the right or the left flank of each animal were graded and recorded.
Number of animals:
3 females
Details on study design:
The rabbit was chosen because of its acceptance as a predictor of irritant/corrosive effects of chemicals in man and the recognition by regulatory authorities that this species is suitable for skin irritation studies.
The number of animals per group is the minimum number enabling an accurate assessment of the studied toxicological effect.
Approximately 24 hours before the test, fur was removed by closely clipping the dorsal area of the trunk of the animals (at least 14 cm x 5 cm). Care was taken to avoid abrading the skin, and only animals with healthy, intact skin were used.
Three test patches were applied sequentially to separate skin sites on the animal. The first patch was removed after three minutes. Since no serious skin reaction was observed, a second patch was applied at a different site and removed after one hour. Since the observations at this stage indicated that exposure could humanely be allowed to extend to four hours, a third patch was applied and removed after four hours and any responses were graded.
Since no corrosive effect was observed in the initial test, the irritant or negative response was confirmed using two additional animals, each with one patch, for an exposure period of four hours.
For the initial test in one animal, due to the colouration of the treatment sites, the application site was not examined immediately after the patch has been removed. One hour, 24 hours, 48 hours and 72 hours approximately after patch removal dermal reactions on the right or the left flank of each animal were graded and recorded.
At the end of the study, euthanasia of animals was performed by an overdose of sodium pentobarbital injected by the intravenous route. No necropsy was performed at the end of the study.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #3
Score:
ca. 0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Score:
ca. 0
Max. score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
The application of the test item induced a dark brown to black colouration of the application site due to the same colouration of the test item. The application site was rinsed using a waterlogged gauze.
There was no cutaneous lesion in any animal at all times of examination.
Mean Indices were 0 in 3 out of 3 animals, therefore Mean Index of erythema and oedema was 0.
Other effects:
There was no change in body weight gain between D1 and D4.

Any other information on results incl. tables

Acute skin lesions - Individual scores - Test item - Local observations

Clinical signs

(range of scores; normal score)

 

Time

Animal serial number

Erythema and eschar (0-4 ;0)

Timmediate

1

2

3

4

5

T 1H

NE

NE

NE

NE

NE

T 24H

0

0

0

0

0

T 48H

0

0

0

0

0

T 72H

0

0

0

0

0

Oedema (0-4 ;0)

T 1H

0

0

0

0

0

T 24H

0

0

0

0

0

T 48H

0

0

0

0

0

T 72H

0

0

0

0

0

NE: not evaluable.

 

Mean Index (M.I.)

Treatment

Animal number

Erythema

Oedema

Test item

130407- T 3MIN

0

0

Test item

130407- T 1H

0

0

Test item

130407- T 4H

0

0

Test item

130408 - T 4H

0

0

Test item

130409 - T 4H

0

0

 

Effect on body weight (individual values)

Treatment

Animal number

 

D1

D4

 

Test item

130407

1.898

2.040

 

 Test item

130408

2.397

2.380

 

 Test item

130409

2.120

2.360

 

Results expressed in kg

D: Day

 

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Under the experimental conditions adopted, "hydrate de carbone et sucres, hexitol, anhydro" LAB 4623 (Batch No. SMOU/13/06) was found to be non irritant for the skin of the rabbit.
Classification according to Council Directive No. 67/548/EEC and subsequent amendments and CLP Regulation No. 1272/2008:
Symbol: none is required.
Indication of danger: none is appropriate.
Risk phrase: none is applicable.
Executive summary:

The aim of the study was to determine any irritant property and/or degree of corrosion of "hydrate de carbone et sucres, hexitol, anhydro" LAB 4623 (Batch No. SMOU/13/06) in the rabbit following a single semi-occluded application to intact skin in accordance with General Requirements of O.E.C.D Guideline No. 404 (April 24, 2002), method B4 of Commission Directive No. 2004/73/EC (April 29, 2004) adapting to technical progress for the 29th Council Directive No. 67/548/EEC and

subsequent amendments and of Council Regulation No. 440/2008 (30th May 2008) and Regulation No. 1907/2006 (REACH).

Three animals were used for the study.

0.5 mL of test item was applied on the skin.

Semi-occlusive dressings held the test item in place for 3 minutes, 1 hour and 4 hours on the skin of the first animal and for 4 hours for the two other animals.

Any cutaneous lesion was evaluated approximately one hour, 24, 48 and 72 hours after removal of the dressing.

Mean indices were calculated from results obtained from each rabbit at times 24, 48 and 72 hours.

The application of the test item induced a brown colouration of the application site. The application site was rinsed using a waterlogged gauze.

There was no cutaneous lesion in any animal at all times of examination.

Mean Index of erythema and oedema was 0.

There was no change in body weight gain.

Conclusion: Under the experimental conditions adopted, "hydrate de carbone et sucres, hexitol, anhydro" LAB 4623 was found to be non irritant for the skin of the rabbit. Substance was not classificied according to Council Directive No. 67/548/EEC and subsequent amendments and CLP Regulation No. 1272/2008.