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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:
The study was performed between 10 February 2010 and 24 February 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009

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)
Remarks:
Date of Inspection: 15 September 2009 Date of Signature: 26 November 2009

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source:
New Zealand White rabbits were supplied by Harlan Laboratories UK Ltd, Hillcrest, Belton, Loughborough, UK.

- Age at study initiation:
Twelve to twenty weeks old.

- Weight at study initiation:
At the start of the study the animals weighed 2.26 or 2.42 kg

- Housing:
The animals were individually housed in suspended cages.

- Diet (e.g. ad libitum):
2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK ad libitum.

- Water (e.g. ad libitum):
ad libitum

- Acclimation period:
At least Five days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C):
17 to 23°C

- Humidity (%):
30 to 70%
- Air changes (per hr):
The rate of air exchange was at least fifteen changes per hour.

- Photoperiod (hrs dark / hrs light):
The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours 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 applied:
0.5 ml

- Concentration:
Neat

VEHICLE
- Amount applied:
Not applicable

- Concentration:
Not applicable.

- Lot/batch no.:
Not applicable
Duration of treatment / exposure:
4 hours
Observation period:
14 days
Number of animals:
2
Details on study design:
TEST SITE
- Area of exposure:
On the day of the test a suitable test site was selected on the back of each rabbit.

- % coverage:
Not given in study report.

- Type of wrap if used:
Test material was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin.


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
Any residual test material removed by gentle swabbing with cotton wool soaked in distilled water.

- Time after start of exposure:
4 hours.


SCORING SYSTEM:
Immeadiately and approximately one hour following the removal of the patches, and 24, 48, 72 hours, 7 and 14 days later, the test sites were examined for evidence of primary irritation and scored according to the following scale (table below).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal: 68871 Male
Time point:
other: Max at 24, 48, 72 hours, 7 and 14 days
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
other: Erythema/Eschar Formation
Basis:
animal: 68872 male
Time point:
other: Max at 24, 48, 72 hours, 7 and 14 days
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
other: Oedema Formation
Basis:
animal: 68871 male
Time point:
other: Max at 24, 48, 72 hours, 7 and 14 days
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
other: Oedema Formation
Basis:
animal: 68872 male
Time point:
other: Max at 24, 48, 72 hours, 7 and 14 days
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The individual scores for erythema/eschar and oedema are given in remarks on results including tables and figures.
Well-defined erythema and very slight oedema were noted at both treated skin sites at the 24-hour observation with well-defined erythema and slight oedema noted at the 48 and 72-hour observations. Loss of skin elasticity and flexibility was noted at both treated skin sites at the 72-hour observation. Crust formation, preventing accurate evaluation of erythema and oedema, was noted at both treated skin sites at the 7-day observation. Slight desquamation was noted at both treated skin sites at the 14-day observation.

Any other information on results incl. tables

Table1              IndividualSkin Reactions

Skin Reaction

Observation Time
(following patch removal)

Individual Scores – Rabbit Number and Sex

Total

68871Male

68872Male

Erythema/Eschar Formation

Immediately

0

0

(0 )

1 Hour

0

0

( 0 )

24 Hours

2

2

4

48 Hours

2

2

( 4 )

72 Hours

2LeLf

2LeLf

4

7 Days

?eCf

?eCf

( 0-8 )

14 Days

0D

0D

( 0 )

Oedema Formation

Immediately

0

0

( 0 )

1 Hour

0

0

( 0 )

24 Hours

1

1

2

48 Hours

2

2

( 4 )

72 Hours

2

2

4

7 Days

?od

?od

( 0-8 )

14 Days

0

0

( 0 )

Sum of 24 and 72-hour Readings (S)       :          14

Primary Irritation Index (S/4)                   :          14/4 = 3.5

Classification                                        :          MODERATE IRRITANT


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

Le =    Loss of skin elasticity

Lf =     Loss of skin flexibility

Cf =    Crust formation

D =     Slight desquamation

?e =    Adverse reaction prevents accurate evaluation of erythema

?od =  Adverse reaction prevents accurate evaluation of oedema

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 EU labelling regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are therefore required.

However according to CLP guidelines, this compound is not classified.

Table 2 Individual Daily and Mean Scores for Dermal Irritation Following 4-Hour Exposure - Required for EU Labelling Regulations

Skin Reaction

Reading (Hours)

Individual Scores – Rabbit Number and Sex

68871Male

68872Male

Erythema/Eschar Formation

24

2

2

48

2

2

72

2

2

Total

 

6

6

Mean Score

 

2.0+

2.0+

Oedema

Formation

24

1

1

48

2

2

72

2

2

Total

 

5

5

Mean Score

 

1.7

1.7


+= positive criteria

 Interpretation of Results

Calculation of Primary Irritation Index and Grading of Irritancy Potential Using the Draize Scheme

The scores for erythema and oedema at the 24 and 72-hour readings were totalled for the two test rabbits (8 values) and this total was divided by four to give the primary irritation index of the test material. The test material was classified according to the following scheme devised by Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of theUnited States,Austin,Texas, p.46-59:

Primary Irritation Index

Classification of Irritancy

     0

Non-irritant

> 0 to 2

Mild irritant

> 2 to 5

Moderate irritant

> 5 to 8

Severe irritant

If irreversible alteration of the dermal tissue is noted in any rabbit, as judged by the Study Director, which include ulceration and clear necrosis or signs of scar tissue, the test material is classified as corrosive to rabbit skin. Classification according to Draize may, therefore, not be applicable.

The results were evaluated according to EU labelling regulations Commission Directive 2001/59/EC for classification and labelling of dangerous substances.


Applicant's summary and conclusion

Interpretation of results:
Category 3 (mild irritant) based on GHS criteria
Remarks:
not classified according to Regulation EC 1272/2008
Conclusions:
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 would be classified as Category 3 (mild irritant) according to GHS criteria. However according to CLP guidelines, this compound is not classified.
Executive summary:

Introduction. 

The study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

OECD Guidelines for the Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 24 April 2002)

Method.

B4 Acute Toxicity (Skin Irritation) of Commission Regulation (EC) No. 440/2008

Results. 

A single 4-hour, semi-occluded application of the test material to the intact skin of two rabbits produced well-defined erythema, slight oedema, loss of skin elasticity and flexibility, crust formation (preventing evaluation of erythema and oedema ) and slight desquamation.

Conclusion. 

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 EU labelling regulations. The symbol "Xi" and risk phrase R 38 "IRRITATING TO SKIN" are therefore required.

However according to CLP guidelines, this compound is not classified.