Registration Dossier

Administrative data

Description of key information

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical. The Pretest was performed to establish the primary irritating threshold concentration of test substance. 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. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 4%.Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 4% in an Open Epicutaneous Test (OET).

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 journals
Qualifier:
according to
Guideline:
other: as mentuined below
Principles of method if other than guideline:
An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical
GLP compliance:
not specified
Type of study:
not specified
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:4%
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:
4% - 0.025 ml
Day(s)/duration:
72 hours
Adequacy of challenge:
not specified
No. of animals per dose:
6–8 male and female guinea pigs
Details on study design:
RANGE FINDING TESTS: The Pretest was performed to establish the primary irritating threshold concentration of test substance. For this, 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. On the basis of preliminary study, the maximal non-irritating concentration selected was 8%. Thus the sensitization test was conducted at a dose of 4% of test chemical.

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: 4% 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:4%
Amount: 0.025ml
- Evaluation (hr after challenge): 24,48 and/or 72h.
Challenge controls:
The 10 controls were either left untreated or treated with 0.1 ml aliquot of the vehicle for 21 days
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
72
Group:
test group
Dose level:
4%
No. with + reactions:
0
Total no. in group:
6
Clinical observations:
no signs of dermal sensitization pbserved
Remarks on result:
no indication of skin sensitisation
Conclusions:
The test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 4% in an Open Epicutaneous Test (OET).
Executive summary:

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

 

The Pretest was performed to establish the primary irritating threshold concentration of test substance. For this, 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. On the basis of preliminary study, the maximal non-irritating concentration selected was 4%. Thus the sensitization test was conducted at a dose of 4% of test chemical.

 

On day 1 during induction, 0.1 ml of test chemical was applied at concentrations of 4% 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.

 

It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 4%.Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 4% in an Open Epicutaneous Test (OET).

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

Various studies were performed on humans and guinea pigs to assess the dermal sensitization potential of Test chemical. The studies are summarized as follows:

 

An Open Epicutaneous Test (OET) was performed on guinea pigs to assess the skin sensitization potential of test chemical. The Pretest was performed to establish the primary irritating threshold concentration of test substance. For this, 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. On the basis of preliminary study, the maximal non-irritating concentration selected was 4%. Thus the sensitization test was conducted at a dose of 4% of test chemical. On day 1 during induction, 0.1 ml of test chemical was applied at concentrations of 4% 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. It was observed that none of the guinea pigs induced contact sensitization at challenge concentration of 4%.Thus, the test chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 4% in an Open Epicutaneous Test (OET).

 

The skin sensitization study was conducted for test chemical to assess its possible contact allergenic potential. For this purpose Human maximization test was performed, using a test material at the concentration of 4% in petrolatum. The test was conducted on 25 human. No skin sensitization effects were observed in any of 25 human volunteers. Therefore the test material was considered to be non-sensitizing to human skin.

 

According to Danish QSAR database, 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 Allergic Contact Dermatitis effects were observed when test chemical was exposed to human and guinea pig skin. Hence, the test chemical can be considered as not sensitizing to skin.

 

The above results were supported by an Open Epicutaneous Test (OET) of test material conducted on guinea pigs. 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 4%.Thus the chemical was considered to be not sensitizing on skin of guinea pigs in an Open Epicutaneous Test (OET).

 

 

In next skin sensitization study, 24 volunteers were treated by maximization test at a concentration of 10% of test chemical in petrolatum. No skin reaction was observed therefore, the test chemical was considered to be not sensitizing to humans.

 

All these studies lead to a conclusion that Test chemical is indeed not sensitizing to skin. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical 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 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. Hence, comparing the above annotations with the criteria of CLP regulation, Test chemical can be classified under the category “Not Classified”.