Registration Dossier

Administrative data

Description of key information

The skin sensitization potential of target chemical was assessed in various experimental studies which were conducted on guinea pigs and humans.Based on the available key data and supporting studies,it can be concluded thatchemical is unable to cause skin sensitization and 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:
key study
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 journal
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
An Open Epicutaneous Test (OET) of the test chemical was conducted on guinea pigs to assess the skin sensitization potential caused by 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:
Concentration:100%, 30%, 10%, 3%, 1%, or 0.3%
Amount: 0.1ml
Day(s)/duration:
3 weeks (0-21 days)
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, open
Vehicle:
other: ethanol, acetone, H20, petroleum, PEG and/or other suitable vehicles
Concentration / amount:
Concentration:5%
Amount: 0.025ml
Day(s)/duration:
on days 21 and 35
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
6-8 guinea pigs
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 21
- Exposure period:24 hours
- Test groups:6-8 guinea pigs
- Control group:3 guinea pigs
- 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: 100%, 30%, 10%, 3%, 1%, or 0.3% in vehicle.
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: 6-8 guinea pigs
- Control group: 3 guinea pigs
- Site: contralateral flank measuring 2 cm2
- Concentrations: Concentration:5%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.
Challenge controls:
Yes concurrent vehicle.
Key result
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
5% (0.025ml)
No. with + reactions:
0
Total no. in group:
8
Clinical observations:
No known signs of skin sensitization were observed.
Remarks on result:
no indication of skin sensitisation
Cellular proliferation data / Observations:
No known signs of skin sensitization were observed.
Interpretation of results:
other: not sensitizing
Conclusions:
None of the treated guinea pigs showed any signs of skin sensitization at challenge concentration of 5%.Thus the chemical was considered to be not sensitizing on skin of guinea pigs in an Open Epicutaneous Test (OET).
Executive summary:

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

 

On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% 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 each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h.

 

None of the treated guinea pigs showed any signs of skin sensitization at challenge concentration of 5%.Thus the chemical was considered to be not sensitizing on skin of guinea pigs in an Open Epicutaneous Test (OET).

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

Various studieshas been investigated for the test chemical to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemicaland its structurally similar read across substance.The predicted data usingDanish QSAR databasethe has also been compared with the experimental data and summarized as below;

 

The peer reviewed journal conducted an Open Epicutaneous Test (OET) of target chemical to assess the skin sensitization potential caused by test chemical. On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 100%, 30%, 10%, 3%, 1%, or 0.3% 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 each concentration to skin areas measuring 2 cm2. The reactions were read after 24,48 and/or 72h. None of the treated guinea pigs showed any signs of skin sensitization at challenge concentration of 5%.Thus the chemical was considered to be not sensitizing on skin of guinea pigs in an Open Epicutaneous Test (OET).

 

A Human maximisation test was carried out to determine skin sensitization potential caused by the chemical. 5% test chemical in petrolatum was applied to the skin of 25 human volunteers and observed for effects till 48 hours. None of the volunteers showed any signs of contact sensitization. Hence, the test chemical was considered to be not sensitizing to the skin of human volunteers.

According to Danish QSAR database, the skin sensitization effects were estimated by using four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra for test chemical. Based on estimation, no skin sensitization reactions were observed in guinea Pig and Human. Therefore, the test chemical was considered to be not sensitizing.

 

The above results were further supported by a maximization test conducted on similar read across chemical on 23 volunteers at a concentration of 4% in petrolatum. No reaction was observed therefore, the test chemical was considered to be not sensitizing to humans.

 

Based on the available data for the target chemical, supporting studies and read across substance,it can be concluded thatchemical is unable to cause skin sensitization and considered as not sensitizing. 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 structurally similar read across substancewere 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.