Registration Dossier

Administrative data

Endpoint:
skin irritation / corrosion, other
Remarks:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
between 23 July 2008 and 26 August 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affcet the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Date of Inspection - 21/08/07 Date of Signature - 15/10/07

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Sponsor's identification: Oxooil LS 13 (CAS No. 68526-92-1)
- Description: Clear colourless liquid
- Date received: 14 July 2008
- Storage conditions : room temperature in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: twelve to twenty weeks old
- Weight at study initiation: 2.0 to 3.5 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum): food (2030 Teklad Global Rabbit diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study.
- Water (e.g. ad libitum): Free access to mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: day 1 To: day 14

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped free from fur using veterinary clippers
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml
- Concentration (if solution): Undiluted as supplied


VEHICLE:
Not applicable
Duration of treatment / exposure:
One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.
Observation period:
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation.
Number of animals:
One rabbit was initially treated. After consideration of the skin reactions produced in the first animal, two additional animals were treated.
Details on study design:
TEST SITE
- Area of exposure: 3 areas each 2.5 cm x 2.5 cm
- % coverage: Not recorded
- Type of wrap if used: surgical adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not applicable
- Time after start of exposure: One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application.


SCORING SYSTEM:
Standard EU Classification and Labelling Scoring system.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean 24, 48 and 72 hours
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Light brown discolouration of the epidermis, Loss of skin elasticity and Loss of skin flexibility at 48, 72 hours and 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: Mean 24, 48 and 72 hours
Score:
1.66
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
3-Minute Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
Well-defined erythema and very slight oedema were noted at the treated skin site at the 24 and 48‑hour observations with very slight erythema and very slight oedema at the 72‑hour observation. Other skin reactions noted at the treated skin site at the 48-hour observation were loss of skin elasticity and light brown discolouration of the epidermis with loss of skin elasticity and crust formation noted at the 72‑hour observation. Slight desquamation was noted at the treated skin site at the 7-day observation. 
The treated skin site appeared normal at the 14-day observation.

1-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 1.
Very slight erythema was noted at the treated skin site one hour after patch removal with well‑defined erythema and very slight oedema noted at the 24, 48 and 72-hour observations. Other skin reactions noted at the treated skin site at the 48 and 72-hour observations were loss of skin flexibility and/or elasticity and light brown discolouration of the epidermis. Moderate desquamation was noted at the treated skin site at the 7-day observation.
The treated skin site appeared normal at the 14-day observation.

 4-Hour Exposure Period:
The individual scores for erythema/eschar and oedema are given in Table 2.
Very slight erythema was noted at all the treated skin sites one hour after patch removal with well defined erythema and very slight to slight oedema at the 24, 48 and 72-hour observations. Very slight erythema was noted at all treated skin sites at the 7‑day observation. Light brown discolouration of the epidermis and loss of skin flexibility and elasticity were noted at all treated
skin sites at the 48 and 72‑hour observations. Crust formation was noted at all treated skin sites at the 7‑day observation. 
All treated skin sites appeared normal at the 14-day observation.

Any other information on results incl. tables

Bodyweight:

Individual bodyweights and bodyweight changes are given in Table 3.

All animals showed expected gain in bodyweight during the study.

Table1               Individual Skin Reactions Following 3-Minute and 1-Hour Exposures

Skin Reaction

Observation Time

Individual Scores - Rabbit Number and Sex

67625Male

3-Minute Exposure

1-Hour Exposure

Erythema/Eschar Formation

1 Hour

0

1

24 Hours

2

2

48 Hours

2LeBr

2LeBr

72 Hours

1LeCf

2LeLfBr

7 Days

0D

0D*

14 Days

0

0

Oedema Formation

1 Hour

0

0

24 Hours

1

1

48 Hours

1

1

72 Hours

1

1

7 Days

0

0

14 Days

0

0

 


D= Slight desquamation

D* = Moderate desquamation

Br = Light brown discolouration of the epidermis

Le = Loss of skin elasticity

Lf = Loss of skin flexibility

Cf = Crust formation

Table2               IndividualSkin ReactionsFollowing 4-Hour Exposure

Skin Reaction

Observation Time

Individual Scores – Rabbit Number and Sex

Total

67625Male

67676Male

67678Male

Erythema/Eschar Formation

1 Hour

1

1

1

(3 )

24 Hours

2

2

2

6

48 Hours

2BrLeLf

2BrLeLf

2BrLeLf

( 6 )

72 Hours

2BrLeLf

2BrLeLf

2BrLeLf

6

7 Days

1Cf

1Cf

1Cf

( 3 )

14 Days

0

0

0

( 0 )

Oedema Formation

1 Hour

0

0

0

( 0 )

24 Hours

1

1

1

3

48 Hours

2

2

2

( 6 )

72 Hours

2

2

2

6

7 Days

0

0

0

( 0 )

14 Days

0

0

0

( 0 )

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

Br = Light brown discolouration of the epidermis

Le = Loss of skin elasticity

Lf = Loss of skin flexibility

Table3               Individual Bodyweights and Bodyweight Change

Rabbit Number
and Sex

Individual Bodyweight (kg)

Bodyweight Change (kg)

Day 0

Day 14

67625Male

2.97

3.12

0.15

67676Male

2.71

3.04

0.33

67678Male

2.50

2.87

0.37

Applicant's summary and conclusion

Interpretation of results:
moderately irritating
Remarks:
Migrated information (but not classifed according to EC Regulation No. 1272/2008) Criteria used for interpretation of results: EU
Conclusions:
In a skin irritation test conducted according to OECD guideline 404 and GLP principles, no corrosive or irreversible effects were noted. The average erythema and oedema score at 24, 48 and 72 hours after exposure was 2 and 1.66 resp, therefore this substance is not classified for skin irritation according to EC Regulation No. 1272/2008. In accordance with EC Directive No. 67/548, the substance should be classified with Xi; R38.
Based on the results obtained in this study, the substance should be labelled with EUH066 – “Repeated exposure may cause skin dryness or cracking”
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)

§        Method B4 Acute Toxicity (Skin Irritation) of Commission Directive 2004/73/EC

Results. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced well-defined erythema and slight oedema. Other skin reactions noted were light brown discolouration of the epidermis, loss of skin elasticity and flexibility and crust formation. All treated skin sites appeared normal at the 14-day observation. No corrosive effects were noted.

Conclusion: 

No corrosive effects were noted. The average erythema and oedema score at 24, 48 and 72 hours after exposure was 2 and 1.66 resp, therefore this substance is not classified for skin irritation according to EC Regulation No. 1272/2008. In accordance with EC Directive No. 67/548, the substance should be classified with Xi; R38. Based on the results obtained in this study, the substance should be labelled with EUH066 – “Repeated exposure may cause skin dryness or cracking”