Registration Dossier

Toxicological information

Skin irritation / corrosion

Currently viewing:

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From October 26, 1999 to November 16, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline 404 and EU guideline B.4. GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

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:
- Purity: approximately 79%
- Lot/batch No.: 876 TK
- Physical state: off white paste
- Storage condition of test material: room temperature, in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 to 16 weeks old
- Weight at study initiation: 2.48 to 3.09 kg
- Housing: The animals were individually housed in suspended metal cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: a minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 ºC
- Humidity (%): 30 to 70 %
- Air changes (per hr): the rate was approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours of darkness.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of the test material.

Duration of treatment / exposure:
4 hour
Observation period:
14 days
Number of animals:
3 animals
Details on study design:
TEST SITE
- Area of exposure: 2.5 x 2.5 cm
- Type of wrap if used: the trunk of the rabbit was wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% Industrial Methylated Spirits.
- Time after start of exposure: 4 hours after application (when the patch was removed).

SCORING SYSTEM:
according to the OECD guideline nº 404.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
72 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Loss of skin elasticity.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Loss of skin elasticity and loss of skin flexibility. At day 7, crust formation was observed. At day 14, slight desquamation was observed.
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
48 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Loss of skin elasticity and loss of skin flexibility. At day 7, crust formation was observed. At day 14, slight desquamation was observed.
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
48 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Loss of skin elasticity
Irritant / corrosive response data:
No corrosive effects were noted.

Any other information on results incl. tables

Individual skin reactions following 4-hours exposure period

 

Skin Reaction

Observation

Time

Individual Scores -Rabbit Number and Sex

(Bodyweight kg)

Total

Erythema/Eschar Formation

 

1Male

(3.09)

198 Male

(2.74)

200 Female

(2.48)

 

1 Hour

0

2

2

( 4 )

24 Hours

0

2

2

4

48 Hours

0

2Le

2le

( 4 )

72 Hours

0

2LeLf

2LeLf

4

7 Days

-

OCf

OCf

( 0 )

1 4 Days

-

OD

OD

( 0 )

Oedema Formation

1Hour

0

2

2

( 4 )

24 Hours

0

1

2

3

48 Hours

0

1

2

( 3 )

72Hours

0

1

1

2

7 Days

-

0

0

( 0 )

14 Days

-

0

0

( 0 )

Sum of 24 and 72-hour Readings (S)                 13

Primary Irritation Index                               13/6 - 2.2

( ): total values not used for calculation of the primary index

Cf: crust formation

D: slight desquamation

Le: loss of skin elasticity

Lf: loss of skin flexibility

- : observation not required

 

Individual daily and mean scores for dermal irritation following 4-hour exposure

 

 

Skin Reaction

Reading (Hours)

Individual Scores - Rabbit Number and Sex

(Bodyweight kg)

 

1Male

(3.09)

198Male

(2.48)

200Female

(2.74)

 

Erythema/Eschar Formation

24

0

2

2

48

0

2

2

72

0

2

2

total

 

0

6

6

Mean Score

 

0.0

2.2

2.0

Oedema Formation

24

0

1

2

48

0

1

2

72

0

1

1

Total

 

0

3

5

Mean Score

 

0.0

1.0

1.7

 

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Well-defined erythema was noted at two treated skin sites one hour after patch removal and at the 24, 48 and 72-hour observations. Slight oedema was noted at two treated skin sites one hour after patch removal. Very slight oedema was noted at two treated skin sites at the 72-hour observation. Mean values (all animals mean of 24/48/72h) are 0.9 oedema and 1.3 for erythema. One treated skin site appeared normal throughout the study. Crust formation was noted at two treated skin sites at the 7-day observation with slight desquamation at these two treated skin sites at the 14-day observation. Hence the substance was not classified for irritation according to GHS, EU.
Executive summary:

The Acute Dermal Irritation/corrosion assay for the test substance was performed in New Zealand rabbits. 0.5 mL of the test material was applied to a site of about 2.5 x 2.5 cm of intact skin of 3 rabbits and covered by semi-occlusive dressing. The administration of the test substance was performed in a sequential manner. The first animal was exposed to the test substance stepwise at three sites of the skin: site 1 for three minutes, site 2 for 1 hour and site 3 for 4 hours. Any residual test substance was removed by swabbing with cotton wool soaked in 74% Industrial Methylated Spirits. After considerations of the skin reactions produced on the first animal, the remaining two animals were exposed to the test substance for 4 hours. The treated areas of the animals were examine for erythema/eschar and oedema as well as other local skin alterations approximately 1, 24, 48, and 72 hours after patch removal. Additional observations were made on days 7 and 14 to assess the reversibility of skin reactions. Dermal alterations were scored according to OECD guideline nº 404. Well-defined erythema was noted at two treated skin sites one hour after patch removal and at the 24, 48 and 72-hour observations. Slight oedema was noted at two treated skin sites one hour after patch removal. Very slight oedema was noted at two treated skin sites at the 72-hour observation.One treated skin site appeared normal throughout the study.Crust formation was noted at two treated skin sites at the 7-day observation with slight desquamation at these two treated skin sites at the 14-day observation. No corrosive effects were noted.