2-[3-(1,3-dihydro-1,3,3-trimethyl-2H-indol-2-ylidene)prop-1-enyl]-1,3,3-trimethyl-3H-indolium acetate

Endpoint summary

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 for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

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 chemical

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 chemical

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 chemical

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.