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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:
22/01/91 - 29/01/1991
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston Sanbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks old
- Weight at study initiation: 2.20 - 2.50 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum (Spillers Rabbit Diet, Dalgety Agriculture Ltd., Almondsbury, Bristol)
- Water (e.g. ad libitum): ad libitum (drinking water)
- Acclimation period: minimum acclimatisation period of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): animal room maintained at 17-22°C
- Humidity (%): relative humidity of 40-61%
- Air changes (per hr): approximately 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light


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 (volume or weight with unit):0.5 g of test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin.



Duration of treatment / exposure:
Four hours
Observation period:
1, 24, 48 and 72 hours following removal of the patches
An additional observation was made on day 7
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: A quantity of 0.5 g of test material was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin.
- Type of wrap: The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.


REMOVAL OF TEST SUBSTANCE
- Corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: four hours


SCORING SYSTEM: according to the scale of Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics"

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 hours
Score:
2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 7 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: crust formation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Remarks on result:
other: haemorrage of dermal capillaries, blanching, light brown discolouration of the epidermis
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 7 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: crust formation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 7 days
Max. score:
4
Remarks on result:
other: adverse reactions prevent evaluation, hardened light brown-coloured scab
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 1, 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 7 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 1, 24, 48, 72 hours
Score:
1 - 2
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 7 days
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 1, 24, 48, 72 hours
Score:
1
Max. score:
4
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 7 days
Max. score:
4
Remarks on result:
other: adverse reactions prevent evaluation of oedema
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: Sum of 24 and 72 hour readings for animal #1, #2, and #3 (S), PDII = S/6
Time point:
other: 24 and 72 hours
Score:
3.5
Max. score:
8
Remarks on result:
other: Classification: moderate irritant
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
2
Max. score:
4
Remarks on result:
other: positive criterion
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1.7 - 2
Max. score:
4
Remarks on result:
other: positive criterion
Irritant / corrosive response data:
Very slight to well-defined erythema was noted at all treated skin sites one hour after patch removal with well-defined erythema at the 24, 48 and 72-hour observations.
Very slight to slight oedema was noted at all treated skin sites one hour after patch removal and at the 24, 48 and 72-hour observations.
Other effects:
Other adverse reactions noted at one treated skin site at these times were haemorrhage of the dermal capillaries, blanching and light brown discolouration of the epidermis. Crust formation was noted at two treated skin sites at the 7-day observation. A hardened light brown-coloured scab, preventing accurate evaluation of erythema and oedema was noted at one treated skin site at the 7-day observation.

Any other information on results incl. tables

Individual reactions

Skin reaction

Observation time 

Individual Scores Rabbit Number and Sex (Bodyweight Kg)

 

 

165 Male

(2.20)

166 Female

(2.27)

170 Female

(2.50)

Total

Erythema/eschar formation 

1 h 

2

1 Hd

1

(4)

 

24 h 

2

2 HdBl

2

6

 

48 h 

2

2 BrBl

2

(6)

 

72 h 

2

2 BrBl

6

 

7 days 

0 Cf

0 Cf

?eSp

(0-4)

Oedema formation 

1 h 

2

1

1

(4)

 

24 h 

2

2

1

5

 

48 h 

2

2

1

(5)

 

72 h 

1

2

1

4

 

7 days 

0

?od

(0-4)

Sum of 24 and 72-Hour readings (S): 21

Primary Irritation Index (S/6):  21/6 = 3.5

Classification: Moderate irritant

( ) = total values not used for calculation of primary irritation index

Cf = crust formation

Hd = haemorrhage of dermal capillaries

?e = adverse reactions prevent evaluation of erythema

Sp = hardened light brown-coloured scab

Br = light brown discolouration of the peidermis

?od = adverse reactions prevent evaluation of oedema

Bl = blanching

Individual daily and individual mean scores for dermal irritation following 4 -hour exposure required for EEC labelling regulations

Skin reaction

Reading (h)

Individual Scores ¿ Rabbit Number and Sex (Bodyweight Kg)

165 Male

(2.20)

166 Female 

(2.27)

170 Female 

(2.50)

 Erythema/eschar formation 

24

2

2

2

 

48

2

2

2

 

72

2

2

 Total

6

6

 Mean Score

2.0+

2.0+

2.0+ 

 Oedema formation 

24

2

2

1

 

48

2

2

1

 

72

1

2

1

 Total

5

6

3

 Mean Score

0.8

2.0+

1.0

+ = positive criterion

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
The test material, DTBP, produced a primary irritation index of 3.5 and was classified as a MODERATE IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material produced positive criteria in 3/3 rabbits according to the EEC labelling regulations and was classified as IRRITANT to rabbit skin. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are therefore required.
Executive summary:

A study was performed to asses the irritancy potential of the test material, DTBP, to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 84/449/EEC /which constitutes Annex V of Council Directive 67/548/EEC).

The results may be used as basis for classification and labelling under Annex VI of Council Directive 67/467/EEC (as adapted to technical progress by Commission Directive 83/467/EEC).

A single 4 -hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and very slight to slight oedema. Other skin reactions noted were haemorrhage of the dermal capillaries, blanching, light brown discolouration of the epidermis, crust formation and hardened light brown-coloured scabs.

The test material produced a primary irritation index of 3.5 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material was also classified as irritant according to EEC labelling regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are therefore required.