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Diss Factsheets

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:
other: Weight of evidence approach based on structurally similar chemicals
Justification for type of information:
Weight of evidence approach based on structurally similar chemicals
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across: supporting information
Reference
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:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to guideline
Guideline:
other: Open Epicutaneous test
Principles of method if other than guideline:
An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the test chemical
GLP compliance:
not specified
Type of study:
open epicutaneous test
Justification for non-LLNA method:
not specified
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation: 300-450g
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
0.1 ml of 20%
Day(s)/duration:
21 days
Adequacy of induction:
other: 1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group.
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
0.025 ml of 20%
Day(s)/duration:
days 21 and days 35
Adequacy of challenge:
other: 1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group
No. of animals per dose:
30 (20: test group ; 10: control group)
Details on study design:
RANGE FINDING TESTS: The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (100, 30, 10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 4%.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups: 20
- Control group: 10
- Site: an area measuring 8 cm2 on the clipped flank skin of the guinea pigs
- Frequency of applications: The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks
- Duration: 21 days (3 weeks)
- Concentrations: 20%
- Amount: 0.1ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on days 21 and 35
- Exposure period:24 hours
- Test groups: 20 guinea pigs
- Control group: 10 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:20%
- Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.

- Other:
1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group, A single application of 0.025 ml of each test concentration (e.g, 100, 30, 10 and 3%) is simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. The minimal irritating and the maximal nonirritating concentrations are determined by an all-or-none criterion. The minimal irritating concentration is defined as the lowest one causing skin irritation. The maximal nonirritating concentration is defined as the highest one not causing macroscopic skin reactions in any of the animals. The estimation of the threshold concentration (minimal irritating and maximal nonirritating concentration) is essential for the evaluation of the allergenic capacity of the test material. On the basis of this pretest, the concentration selected for sensitization test was 20 %.
Challenge controls:
yes concurrent vehicle
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.025ml of 20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.025ml of 20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.025 ml of 20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitizing
Conclusions:
It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 20%. Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).
Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the test chemical.

 

The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 20 %.

On day 1 during induction, 0.1 ml of 20% test chemical was applied to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 20%.Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

Reason / purpose for cross-reference:
read-across: supporting information
Reference
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:
data from handbook or collection of data
Justification for type of information:
data is from peer reviewed journals
Qualifier:
according to guideline
Guideline:
other: Open Epicutaneous test
Principles of method if other than guideline:
An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the test chemical
GLP compliance:
not specified
Type of study:
open epicutaneous test
Justification for non-LLNA method:
not specified
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
- Weight at study initiation: 300-450g
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
0.1 ml of 8%
Day(s)/duration:
21 days
Adequacy of induction:
other: 1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group.
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
0.025 ml of 8%
Day(s)/duration:
days 21 and days 35
Adequacy of challenge:
other: 1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group
No. of animals per dose:
30 (20: test group ; 10: control group)
Details on study design:
RANGE FINDING TESTS: The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (100, 30, 10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 4%.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups: 20
- Control group: 10
- Site: an area measuring 8 cm2 on the clipped flank skin of the guinea pigs
- Frequency of applications: The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks
- Duration: 21 days (3 weeks)
- Concentrations: 8%
- Amount: 0.1ml

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: on days 21 and 35
- Exposure period:24 hours
- Test groups: 20 guinea pigs
- Control group: 10 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:8%
- Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.

- Other:
1 day before starting the induction procedure, the threshold irritating concentration of the test material is estimated on the guinea pigs subsequently used for the experimental group, A single application of 0.025 ml of each test concentration (e.g, 100, 30, 10 and 3%) is simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. The minimal irritating and the maximal nonirritating concentrations are determined by an all-or-none criterion. The minimal irritating concentration is defined as the lowest one causing skin irritation. The maximal nonirritating concentration is defined as the highest one not causing macroscopic skin reactions in any of the animals. The estimation of the threshold concentration (minimal irritating and maximal nonirritating concentration) is essential for the evaluation of the allergenic capacity of the test material. On the basis of this pretest, the concentration selected for sensitization test was 8 %.
Challenge controls:
yes concurrent vehicle
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.025ml of 20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.025ml of 20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
0.025 ml of 20%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No known signs of skin sensitization were observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitizing
Conclusions:
It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%. Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).
Executive summary:

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the test chemical.

 

The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100,30,10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 8%.

On day 1 during induction, 0.1 ml of 8% test chemical was applied to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%.Thus, the test chemicalwas considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

Data source

Reference
Reference Type:
other: Weight of evidence report
Title:
WoE report Dermal irritation potential of Mentha citrata extract based on similar chemicals
Author:
Sustainability Support Services (Europe)
Year:
2018
Bibliographic source:
Sustainability Support Services (Europe), 2018

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: Weight of evidence approach based on structurally similar chemicals
Principles of method if other than guideline:
The weight of evidence report has been prepared based on the read across substances identified based on structural and functional similarity to assess the dermal sensitization potential of Mentha citrata extract
GLP compliance:
not specified
Type of study:
other: Weight of evidence approach based on structurally similar chemicals
Justification for non-LLNA method:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Mentha citrata, ext.
EC Number:
285-378-7
EC Name:
Mentha citrata, ext.
Cas Number:
85085-49-0
Molecular formula:
C10H18O (Linalool) or C12H20O2 (Linalyl acetate)
IUPAC Name:
Mentha citrata, ext.
Test material form:
liquid
Details on test material:
- Name of test material : Mentha citrata, ext.
- IUPAC name : Mentha citrata, ext.
- Molecular formula : C10H18O (Linalool) or C12H20O2 (Linalyl acetate)
- Molecular weight : 154.251- 196.288 g/mol
- Substance type: Organic
- Physical state: Clear liquid (Colorless to pale yellow)
Specific details on test material used for the study:
- Name of test material: Mentha citrata, ext.
- IUPAC name: Mentha citrata, ext.
- Molecular formula: C10H18O (Linalool) or C12H20O2 (Linalyl acetate)
- Molecular weight: 154.251- 196.288 g/mol
- Substance type: Organic
- Physical state: Clear liquid (Colorless to pale yellow)

In vivo test system

Test animals

Species:
guinea pig
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
no data available

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
8%, 20%
Day(s)/duration:
4 weeks
Adequacy of induction:
not specified
Challenge
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
8%, 20%
Day(s)/duration:
24 hours
Adequacy of challenge:
not specified
No. of animals per dose:
no data available
Details on study design:
The study is based on weight of evidence approach from the read across values
Challenge controls:
The study is based on weight of evidence approach from the read across values
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Results
Reading:
1st reading
Hours after challenge:
72
Group:
test chemical
Dose level:
8% ,20%.
Clinical observations:
no signs of dermal sensitization observed
Remarks on result:
no indication of skin sensitisation

Applicant's summary and conclusion

Interpretation of results:
other: not sensiting
Conclusions:

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that Mentha citrata extractwill also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be not sensitizing to skin.
Executive summary:

Based on the available studies for the structurally similar read across chemicals, weight of evidence approach was applied to assess the dermal sensitization potential of Mentha citrate extract.

 

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of the structurally similar chemicals.

The pretest was performed to determine the primary irritating threshold concentration of test substances at various concentrations (e.g, 100, 30, 10 and 3%). In this test, a single application of 0.025 ml of each test concentration was simultaneously performed on one of the areas measuring 2 cm2 of the flank skin previously clipped and marked with a circular stamp. Reactions are read 24 h after the application of the test material. On the basis of pretest, the concentration selected for sensitization test was 8% for the first one and 20% for the second one.

On day 1 during induction, 0.1 ml of 8%, 20% of the structurally similar chemicals were applied to an area measuring 8 cm2 on the clipped flank skin of the guinea pigs. The applications are repeated daily for 3 weeks or done 5 times weekly during 4 weeks, usually on the same skin sites. The application sites were left uncovered and the reactions, if continuous daily applications were performed, can be read 24 h after each application, or at the end of each week. To determine whether or not contact sensitization was induced, all groups of guinea pigs previously treated for 21 days, as well as 10 untreated, or only pretreated with the vehicle, controls are tested on days 21 and 35 on the contralateral flank with the test material. This test was performed by applying with a pipette 0.025 ml of chemical to skin areas measuring 2 cm2. The reactions were read after 24, 48 and/or 72h.

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 8%, 20%.

Both the structurally similar chemicals were considered to be not sensitizing on skin of guinea pigs when tested via an Open Epicutaneous Test (OET).

Based on the available data for the structurally similar read across substances and applying the weight of evidence approach, it can be concluded that Mentha citrata extractwill also tend to behave in a similar manner that of the structurally similar read across substances. Therefore the target chemical was estimated to be not sensitizing to skin.