Registration Dossier

Administrative data

Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on human subjects. Based on the available data for the test chemical and supporting studies, it can be concluded that the test chemical is unable to cause skin sensitization and thus can be considered as not sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “not classified”.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
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
Remarks:
experimental data of read across substances
Justification for type of information:
Data for the target chemical is summarized based on the structurally similar read across chemicals
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
WoE report is based on 3 skin sensitization studies as- WoE-2 and WoE-3.
Skin sensitization of test chemical was determined by performing patch tests on humans.
GLP compliance:
no
Type of study:
not specified
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The Guinea Pig Maximization Test (GPMT) has been carried out as an animal test to predict human sensitization for over a decade and is recommended by international test guidelines such as OECD.
Species:
other: 2. human 3.guinea pig
Strain:
other: 2.not applicable 3.not specified
Sex:
not specified
Details on test animals and environmental conditions:
2. not specified
3. - Weight at study initiation: 300-450g
Route:
other: 2. epicutaneous
Vehicle:
not specified
Concentration / amount:
not specified
Day(s)/duration:
not specified
Adequacy of induction:
not specified
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Remarks:
3.
Concentration / amount:
Concentration: 1%
Amount: 0.1ml
Day(s)/duration:
3 weeks (0-21 days)
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
other: 2. epicutaneous
Vehicle:
not specified
Concentration / amount:
not specified
Day(s)/duration:
not specified
Adequacy of challenge:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Remarks:
3.
Concentration / amount:
Concentration:1%
Amount: 0.025ml
Day(s)/duration:
72 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
2. not specified
3. 30 (20: test group ; 10: control group)
Details on study design:
2.
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 53


B. CHALLENGE EXPOSURE
- No. of exposures: 53

3.
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 1 %.


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: 1%
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: 1%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.
Challenge controls:
2. not specified
3. Yes,concurrent vehicle.
Positive control substance(s):
not specified
Positive control results:
2. not specified
Reading:
other: 2. induction phase
Group:
test group
No. with + reactions:
3
Total no. in group:
53
Clinical observations:
cutaneous lesion
Remarks on result:
no indication of skin sensitisation
Reading:
other: 2. challenge phase
Group:
test group
No. with + reactions:
2
Total no. in group:
53
Clinical observations:
cutaneous lesion
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
1% (0.025ml)
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
Remarks:
3.

3.

No known signs of skin sensitization were observed.

Interpretation of results:
other: not sensitizing
Conclusions:
The test chemical was considered to be not sensitizing to the skin on the basis of summarized studies.
Executive summary:

Data available for the functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

The skin sensitization study was conducted on 53 human subjects to assess the skin sensitization potential of test chemical using patch test.During different phase of the test i.e. Induction and provocation phase, 3/53 and 2/53 test persons ,respectively showed a cutaneous lesion.As these lesions were seen in minimum number of subjects, the test result can be observed to be negative for the test chemical. Therefore test chemical was considered to be not sensitizing to the skin of humans using patch test for Epicutaneous testing.

In another study,an Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of 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 1 %.On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 1% in vehicle 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 1%.Thus the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 1% in an Open Epicutaneous Test (OET).

Based on the above summarized studies for target chemical and its functionally similar read across substances,it can be concluded that the test chemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Data available for the functionally similar read across chemicals has been reviewed to determine the skin sensitization potential of the test chemical. The studies are as mentioned below:

The skin sensitization study was conducted on 53 human subjects to assess the skin sensitization potential of test chemical using patch test.During different phase of the test i.e. Induction and provocation phase, 3/53 and 2/53 test persons ,respectively showed a cutaneous lesion.As these lesions were seen in minimum number of subjects, the test result can be observed to be negative for the test chemical. Therefore test chemical was considered to be not sensitizing to the skin of humans using patch test for Epicutaneous testing.

In another study,an Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of 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 1 %.On day 1 during induction, 0.1 ml of the Indole was applied at concentrations of 1% in vehicle 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 1%.Thus the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 1% in an Open Epicutaneous Test (OET).

Based on the above summarized studies for target chemical and its functionally similar read across substances,it can be concluded that the test chemical is unable to cause skin sensitization and considered as non-skin sensitizer. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Not Classified”.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The skin sensitization potential of test substance and its functionally similar read across substances were observed in various studies. From the results obtained from these studies it is concluded that the chemical is not likely to cause skin sensitization and hence can be classified as non-skin sensitizer.