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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Cross-reference
Reason / purpose:
reference to other study
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1997-04-01 to 1997-05-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A well conducted study according to guidelines and done in compliance with GLP.
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The study was performed inn 1997, prior to the publication of OECD Guideline 429 for the LLNA study and the REACH requirements. The result from the guinea pig maximisation test was conclusive and showed the test substance to be an extreme sensitizer therefore it serves no purpose to repeat the study.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 342-415 grams
- Housing: polypropylene cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 37-66
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Main Study
Intradermal induction - 5%
Topical induction - 100%
Topical challenge - 75%, and 100%
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Main Study
Intradermal induction - 5%
Topical induction - 100%
Topical challenge - 75%, and 100%
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS: intra dermal (1%, 5%, 10%, 25%); topical (25%, 50%, 75%, 100%)

MAIN STUDY
A.INDUCTION EXPOSURE
- No. of exposures: intra dermal duplicate injections of:
a)Freund’s Complete Adjuvant plus distilled water (1:1 ratio)
b) 5% w/v formulation of the test material in arachis oil BP
c)5% w/v formulation of the test item in a 1:1 preparation of Freund’s Complete Adjuvant plus distilled water.

A single topical application (100% test material) for 48 hours, on day 7 was also applied.
- Test group: 1 test group of 20 animals
Control group: vehicle control
- Site: shoulder
- Duration: same as test group

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: 21
- Exposure period: 24 hours
- Test groups: 1 test group of 20 animals
- Control group: 1 group of 10 animals
- Site: left and right flank
- Concentrations: 75% in arachis oil, 100%
- Evaluation (hr after challenge): 24 and 48 hours after removal of the patch


Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
75%
No. with + reactions:
16
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75%. No with. + reactions: 16.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
75%
No. with + reactions:
11
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75%. No with. + reactions: 11.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100%
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100%. No with. + reactions: 18.0. Total no. in groups: 20.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100%
No. with + reactions:
14
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100%. No with. + reactions: 14.0. Total no. in groups: 20.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Skin Reactions Observed After Intradermal Induction

Very slight to well defined erythema was noted at the intra dermal induction sites of all test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the intra dermal induction sites of nine control group animals at the 24-hour observation and in eight control group animals at the 48-hour observation.

Skin Reactions Observed After Topical Induction

After topical induction, very slight to well-defined erythema and incidents of very slight to slight oedema were noted at the induction sites of all test group animals at the 1and 24-hour observations. Bleeding from the intra dermal induction sites was noted in seven test group animals at the 1-hour observation. Other skin reactions noted were peeling of the skin and small superficial scattered scabs.

Bleeding from the intra dermal sites was noted in five of the control group animals at the 1 hour observation. No signs of erythema or oedema were noted at the treatment sites of the control group animals at either the 1or 24 hour observation.

Skin Reactions Observed After Topical Challenge

Undiluted as Supplied

Positive skin responses (very slight – well defined erythema) and incidents of very slight to slight oedema were noted at the challenge sites of 18 of the test group animals after 24 hours and 14 after 48 hours. Peeling of the skin was noted at the challenge sites of three test group animals at the 48 hour observation.

No skin reactions were noted at the challenge sites of the control group animals after either 24 or 48 hours.

 

75% v/v in Arachis Oil

Positive skin responses (very slight – well defined erythema) and incidents of very slight to slight oedema were noted at the challenge sites of 16 of the test group animals after 24 hours and 11 after 48 hours. Peeling of the skin was noted at the challenge sites of three test group animals at the 48 hour observation.

No skin reactions were noted at the challenge sites of the control group animals after either 24 or 48 hours.

 

 

No effects on the bodyweight gains of guinea pigs in the test group, between day 0 and day 24 were observed.

 

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
2,2,6,6-Tetramethyl-4-oxopiperidinooxy was sensitizing to guinea pigs in a maximization study at a challenge concentration of 75%.
Executive summary:

A GLP study was performed to assess the contact sensitisation potential of 2,2,6,6,-tetramethyl-4-oxopiperidinooxy in the albino guinea pig. The study was performed in accordance with OECD guideline 406.

Twenty test and ten control animals were used in the main study.

The concentrations of test materials in the induction and the challenge phases were selected based on the results of sighting tests and were as follows:

Intra dermal induction: 5% w/v in arachis oil BP

Topical Induction: Undiluted as supplied

Topical Challenge: undiluted as supplied and 75% in arachis oil.

After topical induction, very slight to well defined erythema and very slight to slight oedema were noted at the induction sites of all test group animals at the 1 and 24 hour observations.

On challenge, a positive skin response was observed in 90% of the test animals after 24 hours and 70% after 48 hours. No positive skin reactions were noted in the control animals after 24 or 48 hours.

Based on the results the test material, 2,2,6,6-tetramethyl-4-oxopiperidinooxy, is classified as an extreme sensitiser to guinea pig skin.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Principles of method if other than guideline:
Dermal observations made during topical sighting tests for a skin sensitisation study.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48 h
Score:
0.5
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
edema score
Basis:
animal #1
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.
Irritation parameter:
edema score
Basis:
animal #2
Time point:
48 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks:
48 hours exposure to 100% test item.

Any other information on results incl. tables

The results for the topical sighting tests for induction application are shown in Tables 1 and 2 below.

Table 1. Topical sighting test for induction application (48-hour exposure) – individual skin reactions.

Animal Identification

Concn of test material* (%v/v)

Skin Reaction (Hours after removal of patches)

1

24

48

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

E

100

2

1

STA

1

1

STA

0

0

STA

75

2

1

STA

1

1

STA

0

0

STA

50

1

0

-

1

0

-

0

0

-

25

0

0

-

0

0

-

0

0

-

F

100

2

1

STA

1

1

STA

0

0

STA

75

2

1

STA

1

1

STA

0

0

STA

50

1

0

STA

1

0

STA

0

0

STA

25

1

0

STA

1

0

-

0

0

-

*Vehicle: Arachis oil BP

Er = erythema  Oe = oedema   - = no reaction noted   STA = amber coloured staining

 

The undiluted test material was selected for the main study topical induction.

 

Table 2. Topical sighting test for induction application (24-hour exposure) – individual skin reactions.

Animal Identification

Concn of test material* (%v/v)

Skin Reaction (Hours after removal of patches)

1

24

48

Er

Oe

Other

Er

Oe

Other

Er

Oe

Other

G

100

1

0

STA

0

0

STA

0

0

-

75

1

0

STA

0

0

-

0

0

-

50

0

0

-

0

0

-

0

0

-

25

0

0

-

0

0

-

0

0

-

H

100

1

0

STA

0

0

-

0

0

-

75

1

0

-

0

0

-

0

0

-

50

1

0

-

0

0

-

0

0

-

25

1

0

-

0

0

-

0

0

-

*Vehicle: Arachis oil BP

Er = erythema  Oe = oedema   - = no reaction noted   STA = amber coloured staining

 

The undiluted test material and 75% v/v in arachis oil BP were selected for the main study topical challenge.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met