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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose:
reference to same study
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Guinea pigs were induced with 5 intradermal injections of the compound mixed with Freund's Complete Adjuvant (FCA) into the neck on days 0, 2, 4, 7 and 9. The test group and the control animals are challenged on days 21 and 35 and reactions are read after 24, 48 and 72 hours.
GLP compliance:
not specified
Type of study:
Freund's complete adjuvant test
Justification for non-LLNA method:
The method allows to determine sensitizing reactions in guinea pigs.
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Route:
intradermal
Vehicle:
other: Freund's Complete Adjuvant
Concentration / amount:
0.1 mL of a 5% emulsion
Day(s)/duration:
20
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
not specified
Concentration / amount:
0.025 mL
Day(s)/duration:
at day 21 and 35
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
10
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 5
- Exposure period: 20 days
- Test groups: yes
- Control group: yes
- Frequency of applications: days 0, 2, 4, 7 and 9
- Concentrations: 5% emulsion in Freund's Complete Adjuvant

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 21 and 35
- Test groups: yes
- Control group: no
- Site: 2 cm2
- Concentrations and vehicle not clearly specified, but the "primary non-irritant solution" was used (which is stated to be 10% after single and after repeated application).
- Evaluation (hr after challenge): 24, 48 and 72
Challenge controls:
no
Positive control substance(s):
no
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
non-irritant dose
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:
test group
Dose level:
non-irritant dose
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The substance should not be classified as a skin sensitizer.
Executive summary:

In the current study the capacity for allergic sensitization by the test item was determined by the intradermal test with Freund's Complete Adjuvant (FCAT). Ten guinea pigs were used and a control group was included in the study. Induction consisted of 5 intradermal injections of the compound mixed with Freund's Complete Adjuvant (FCA). Injections occured into the neck on days 0, 2, 4, 7 and 9.

The test group and the control animals were challenged epicutaneously on days 21 and 35 and reactions were read after 24, 48 and 72 hours.

No effects were observed. Under the conditions of the study, the test material exhibited no sensitizing potentialities.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Open Epicutaneous Test (OET)
Principles of method if other than guideline:
During the induction phase 100, 30, 10 or 3 of the test item in ethanol is applied to the animals and left uncovered. Applications are repeated daily for 21 consecutive days. Skin irritation is evaluated at 7, 14 and 21 days. Challenge is done on days 21 and 35 on the contralateral flank (with 10% (minimal irritation concentration) and 3%) and left uncovered. Reactions were read at 24, 48 and 72 hours after application.
GLP compliance:
not specified
Type of study:
open epicutaneous test
Justification for non-LLNA method:
The method allows to determine the minimal sensitizing concentration necessary for inducing allergic contact hypersensitivity and the minimal eliciting concentration necessary to cause a positive reaction.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, open
Vehicle:
other: ethanol
Concentration / amount:
3, 10, 30 and 100%
Day(s)/duration:
21
Adequacy of induction:
not specified
Challengeopen allclose all
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol
Concentration / amount:
10 and 3 %
Day(s)/duration:
at day 21
No.:
#2
Route:
epicutaneous, open
Vehicle:
other: ethanol
Concentration / amount:
10 and 3%
Day(s)/duration:
at day 35
No. of animals per dose:
6
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period: 20 days
- Test groups: 4
- Control group: 1
- Site: 8 cm2
- Frequency of applications: daily
- Concentrations: 3, 10, 30 and 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: day 21 and 35
- Exposure period: week 3 and 5
- Test groups: 4 + control group of induction exposure
- Control group: no
- Site: contralateral flank - 2 cm2
- Concentrations: minimal irritating concentration: 10 and 3%
- Evaluation (hr after challenge): 24, 48 and 72
Challenge controls:
no
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100, 30, 10 and 3%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
24
Group:
test group
Dose level:
100, 30, 10 and 3%
No. with + reactions:
0
Total no. in group:
6
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The substance is not skin sensitising.
Executive summary:

In an open epicutaneous test (OET) on guinea pigs the capacity of the test material to induce allergenic sensitization was assessed in 4 test groups of 6 animals and a control group. During the induction phase 100, 30, 10, and 3% of the test item in ethanol was applied to the clipped flank and left uncovered. The applications were repeated daily for 21 consecutive days. Skin irritation was evaluated at 7, 14 and 21 days. A challenge application was performed on days 21 and 35 on the contralateral flank. The minimal irritation concentration (10%) and some lower concentrations were used and left uncovered. Reactions were read after 24, 48 and 72 hours after application. The test material is considered allergenic at a concentration when at least 1 out of 6 animals of the concentration group shows positive reactions with non-irritant concentrations used for challenge.

No positive reactions were observed at any concentration, not after induction and not after the first or the second challenge. Therefore, the test material is considered not skin sensitizing in guinea pigs.