Registration Dossier

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
No Guideline stated, no GLP statement available, more stringent test conditions as requires in OECD guidelines

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
more stringed test conditions
Principles of method if other than guideline:
NA
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Purity batch
> 99.0 % 7.32% active oxygenBatch 247408973
99.27 % 9407226339; 247408999
99.6 % 0410105225413
> 97 % 4289070300; 0419101226056
99.1 % 11600 0010-108
99.3 % 247413988
99.4 % 7.35 % active oxygen Batch 247409800
98.9 % 0707518256
> 99.1 % 247412384
98.5 % 0707603153
99.0 % 1703465433
99.5 % 150726; 247413309
99.3 % 000055055

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Kuiper's Rabbit Ranch, Gary, Indiana
Housing: rabbits were individually housed in hanging wire-mesh cages in temperature and humidity controlled quarters
Conditioning period: 6 days prior to study initiation
Diet: ad libitum
Water: ad libitum
Body weights prior to administration: 2010 to 2770 g

Test system

Type of coverage:
occlusive
Preparation of test site:
other: 3 animals clipped and 3 animals abraded
Vehicle:
unchanged (no vehicle)
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 mL


Duration of treatment / exposure:
24 hrs
Observation period:
24 and 72 hrs after application
Number of animals:
6 (3 male, 3 female)
Details on study design:
TEST SITE
- Area of exposure: back of each rabbit
- % coverage: 20 - 30 % of the body surface
- Type of wrap if used: the application sites were covered with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. A collar was also applied.


REMOVAL OF TEST SUBSTANCE
- Washing: the sites were washed with tepid tap water

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
33229/M
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
33198/F
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
33216/F
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.8
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
33229/M
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
33198/F
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
33216/F
Time point:
24/48/72 h
Score:
0.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: intact skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
33197/M
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
33225/M
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
33192/F
Time point:
24/48/72 h
Score:
1.75
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.9
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
33197/M
Time point:
24/48/72 h
Score:
1.5
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
33225/M
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
33192/F
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
1.25
Max. score:
4
Reversibility:
no data
Remarks on result:
other: abraded skin
Remarks:
48 h were not assessed
Irritant / corrosive response data:
NA
Other effects:
NA

Any other information on results incl. tables

No remarks

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Following study results and the OECD GHS (1272/2008) criteria, tert.-Butylperoxy- 2-ethylhexanoat is not considered as an primary skin irritant. With regard to Commission Directive 67/548 the results represents a borderline case.
Executive summary:

Tert.-Butylperoxy- 2-ethylhexanoat was tested to three male and 3 female New Zealand White rabbits similar to OECD guideline 404 (but more stringed test conditions). The hair was removed from the back of each rabbit. (20 - 30 % of the body surface) with an electric clipper. The skin of 3 of the rabbits was abraded with a scalpel blade. The abrasion penetrated the stratum corneum, but were not deep enough to cause bleeding.

A volume of 0.5 mL of the test material was applied to the back of each rabbit under a one inch square gauze patch. The application sites were covered with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. A collar was also applied. Following 24 hours of application, the bandages and collars were removed and the sites were washed with tepid tap water and examined for skin irritation. The examinations were repeated at 72 hours.

The table below presents the grade of effect with time.

 

 

Intact skin

Abraded Skin

Observations

Value

24 hrs

72 hrs

24 hrs

72 hrs

Erythema, Eschar Formation

0

 

 

1/3

1/3

1

1/3

1/3

1/3

 

2

2/3

2/3

1/3

2/3

3

 

 

 

 

4

 

 

 

 

Oedema Formation

0

1/3

 

1/3

1/3

1

2/3

1/3

2/3

1/3

2

 

2/3

 

1/3

3

 

 

 

 

4

 

 

 

 

Calculation for Primary Skin Irritation Score (Score = The average of all the erythma scores plus the average of all the oedema scores): (18.5 ÷ 12) + (12 ÷ 12) = 2.5.

In this study, the test conditions were more stringed as required in OECD guidelines and can thus be regarded as worst case scenario.

The conditions in this study were 24 hours occlusive treatment, whereas in the OECD guideline 4 hours semi-occlusive treatment is requested.