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Description of key information

Hanzawa, 2008a: Read-across to a substance with a similar structure.

Under the conditions of the study no skin reaction was observed in the exposure group, and thus the test material was determined to be non-sensitizing.

Supporting Study:

Under the conditions of the study, the test material is not considered to be a skin sensitiser.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Guineapig maximisation test.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Existing data already available using a non-LLNA method.
Test material information:
Composition 1
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
epicutaneous, semiocclusive
Vehicle:
not specified
Concentration / amount:
5 %
Day(s)/duration:
Not specified
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
not specified
Concentration / amount:
2.5 %
Day(s)/duration:
Sensitisation evaluated after 24 and 48 hours post patch removal.
Adequacy of challenge:
not specified
No. of animals per dose:
10 for the treatment group, 5 for the control group
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1
- Concentrations: 5 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Concentrations: 2.5 %
- Evaluation (hr after challenge): 24 and 48 hours
Challenge controls:
The control group without induction was treated with the challenge.
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
2.5 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
2.5 %
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
negative control
Dose level:
2.5 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
2.5 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: Not sensitising in accordance with EU criteria
Conclusions:
Under the conditions of the study, the test material is not considered to be a skin sensitiser.
Executive summary:

The sensitisation potential of the test material was determined in a guinea pig maximisation test.

Ten guinea pigs were treated with the test material at 5 % concentration for the induction phase, five guinea pigs were untreated as the negative control group. All fifteen animals were treated with a dose of 2.5 % concentration of test material for the challenge phase and were observed for sensitisation at 24 and 48 hours after removal of the patch.

No signs of sensitisation were observed in any of the animals in the treatment or control groups and in conclusion under the conditions of this study the test material was not considered to be a skin sensitiser.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 January 1989 to 14 April 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Study conducted on read-across material
Justification for type of information:
Read-across from a structurally similar substance.
Reason / purpose:
other: Read-across target
Related information:
Composition 1
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
See below.
Principles of method if other than guideline:
The study does not state whether the female animals are nulliparous and non-pregnant. Grouping was not a random procedure. The study does not justify how the dose level was selected; it should be the highest concentration to cause mild-to-moderate skin irritation.
GLP compliance:
no
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Existing data already available using a non-LLNA method.
Test material information:
Composition 1
Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 5 weeks.
- Weight at study initiation: 310.5 to 366.8 g
- Housing: Groups of 5, in bracket cages made from aluminium.
- Diet: Solid feed for test animals, ad libitum.
- Water: Tap water, ad libitum.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 26 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): 10 to 15 cycles per hour.
- Photoperiod (hrs dark / hrs light): 12 hours from 07:00 until 19:00 hours, with an intensity of between 200 and 500 lux.
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
- Induction exposure: 20 % intradermal induction; 20% epidermal induction
- Challenge exposure: 10 %
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
- Induction exposure: 20 % intradermal induction; 20% epidermal induction
- Challenge exposure: 10 %
No. of animals per dose:
10 per dose for the test material group and the positive control.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- Site and: An area of approximately 6 cm x 4 cm was prepared on the back of the neck of each animal. Injections were administered over an area of approximately 2 cm x 4 cm.
- Preparation: The exposure site was shaved on Days 1 and 6 prior to intradermal and epidermal inductions.
- Intradermal induction: On Day 2, 0.1 mL of the FCA emulsion fluid, 0.1 mL of the test material solution (or positive control substance), and 0.1 mL of the test material/FCA emulsion fluid (or positive control substance/FCA emulsion fluid) were intradermally induced in pairs.
- Epidermal induction: White petrolatum containing 10.0 % SLS was also applied to the skin on Day 6. On Day 7 cotton lint (2 cm x 4 cm) that was coated with 0.5 mL of the test material (or positive control substance) of the specified concentration was applied onto the same site, and fixed in place using tape.
- Duration: The epidermal induction was occlusively dressed for 48 hours.

B. CHALLENGE EXPOSURE
- Site: An area of approximately 5 cm x 10 cm on the right side of the abdomen.
- Preparation: Shaved on Day 26.
- Challenge exposure: On Day 27 cotton lint (2 cm x 2 cm each) that was immersed in 0.2 mL of the test material (or positive control substance) was applied to the shaved site, and fixed in place using tape.
- Exposure period: 24 hours.
- Evaluation (hr after challenge): Observations of the application sites were made 24 hours and 48 hours after removal of the occlusive adhesion, and sensitivity was assessed.
Challenge controls:
Two challenge controls were performed, one for the test material and one for the positive control.
- No. of animals per dose: 5 animals per dose.
- Concentrations: Test material, 10 %; Positive control, 0.1 %.
Positive control substance(s):
yes
Remarks:
2,4-Dinitrochlorobenzene (DNCB)
Positive control results:
Severe erythema and edema were observed 24 hours after challenge exposure, and escharosis was observed 48 hours after challenge exposure, indicating a positive result.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.1%. No with. + reactions: 10.0. Total no. in groups: 10.0. Clinical observations: None.

Observations

- Clinical observations: During the study period, there were no abnormalities in clinical signs observed.

- Body weight: A decrease in body weight was observed in 7/10 of the treated animals, 2/5 animals in the control group 24 hours after removal of the challenge exposure application (Day 29). 24 hours after removal of the challenge exposure application (Day 29) of the positive test substance DNCB, a decrease in body weight was observed in 8/10 of the animals in the study group and 5/5 of the animals in the control group. The cause is not clear, but since a similar phenomenon was observed in the control group as well, it was determined that this decrease in body weight did not result from the test material.

- Challenge exposure: Skin reaction was not observed in 10% challenge exposure of the test material solution.

Table 1: Skin Reaction Results

Test Group

Animal No.

Score

24 hours

48 hours

Sensitization Test Material (20% intradermal induction; 20% epidermal induction; 10% challenge exposure)

1

0

0

2

0

0

3

0

0

4

0

0

5

0

0

6

0

0

7

0

0

8

0

0

9

0

0

10

0

0

Mean

0

0

No. with positive reaction

0/10

0/10

Positive Reaction Rate

0

0

Challenge Control Test Material (10% challenge exposure)

11

0

0

12

0

0

13

0

0

14

0

0

15

0

0

Mean

0

0

No. with positive reaction

0/5

0/5

Positive Reaction Rate

0

0

Positive Control (DNCB 0.1% intradermal induction, epidermal induction and challenge exposure)

31

3

3

32

3

3

33

3

3

34

2

3

35

3

3

36

3

3

37

3

3

38

3

3

39

3

3

40

3

3

Mean

2.9

3.0

No. with positive reaction

10/10

10/10

Positive Reaction Rate

100

100

Challenge Control (DNCB 0.1%, challenge exposure)

41

0

0

42

0

0

43

0

0

44

0

0

45

0

0

Mean

0

0

No. with positive reaction

0/5

0/5

Positive Reaction Rate

0

0

Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Under the conditions of the study no skin reactions were observed and it was concluded that the test material has no skin sensitization potential.
Executive summary:

The potential for the test material to cause skin sensitization was assessed in a Guinea pig maximisation test, performed according to a methodology similar to that specified in the OCED guideline, 406. Ten Guinea pigs were exposed to the test material. The induction exposure was performed at a concentration of 20 % via intradermal injection followed by epicutaneous application and occluded for 48 hours. The challenge exposure was performed by epicutaneous application at a concentration of 10 % and occluded for 24 hours. Dermal reactions were scored at 24 and 48 hours post challenge. Additional observations were made for clinical signs of toxicity and body weight change. A positive control, 2,4-Dinitrochlorobenzene (DNCB), was run concurrently. Challenge controls were run for both the exposure group and the positive control. Under the conditions of the study no skin reaction was observed in the exposure group, and thus the test material was determined to be non-sensitizing.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted on read-across material.
Justification for type of information:
RAAF report to be provided.
Reason / purpose:
read-across source
Related information:
Composition 1
Reference:
Composition 0
Test material information:
Composition 1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
10 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
None
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.1 %
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.1 %
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
None
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Hanzawa, 2008a: Read-across to a substance with a similar structure.

The potential for the test material to cause skin sensitization was assessed in a Guinea pig maximisation test, performed according to a methodology similar to that specified in the OCED guideline, 406. Ten Guinea pigs were exposed to the test material. The induction exposure was performed at a concentration of 20 % via intradermal injection followed by epicutaneous application and occluded for 48 hours. The challenge exposure was performed by epicutaneous application at a concentration of 10 % and occluded for 24 hours. Dermal reactions were scored at 24 and 48 hours post challenge. Additional observations were made for clinical signs of toxicity and body weight change. A positive control, 2,4-Dinitrochlorobenzene (DNCB), was run concurrently. Challenge controls were run for both the exposure group and the positive control. Under the conditions of the study no skin reaction was observed in the exposure group, and thus the test material was determined to be non-sensitizing.

Supporting Study

The sensitisation potential of the test material was determined in a guinea pig maximisation test.

Ten guinea pigs were treated with the test material at 5 % concentration for the induction phase, five guinea pigs were untreated as the negative control group. All fifteen animals were treated with a dose of 2.5 % concentration of test material for the challenge phase and were observed for sensitisation at 24 and 48 hours after removal of the patch.

No signs of sensitisation were observed in any of the animals in the treatment or control groups and in conclusion under the conditions of this study the test material was not considered to be a skin sensitiser.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Regulation (EC) No. 1272/2008, the test material does not meet the criteria for classification as a skin sensitizer.