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Description of key information

The skin sensitization potential of target chemical was assessedin various experimental studies which were conducted on guinea pigs and humans.The predicted data usingDanish QSAR databasehas also been compared with the experimental data.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)
Remarks:
in vivo
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 publication
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Maximization test was conducted on humans to determine the sensitization potential of test chemical.
GLP compliance:
not specified
Type of study:
other: human Maximization test
Justification for non-LLNA method:
Currently no LLNA study is available for assessment. The human Maximization test 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:
human
Strain:
other: not applicable
Sex:
male
Details on test animals and environmental conditions:
no data
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
4 % in petrolatum
Day(s)/duration:
5 days
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
4 % in petrolatum
Day(s)/duration:
48 and 72 hours
Adequacy of challenge:
not specified
No. of animals per dose:
25 healthy male patients.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures:3 days
- Exposure period: 48 h periods.
- Test groups:25
- Control group:No
- Site:Forarms
- Frequency of applications: for five alternate days, 48 h periods
- Duration:5 days
- Concentrations:4% in petrolatum

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge: 10 days after challenge exposure period
- Exposure period:48-hrs
- Test groups:25
- Control group:
- Site: applied to fresh sites on the back
- Concentrations: 4% in petrolatum
- Evaluation (hr after challenge): 48 and 72 h
Challenge controls:
No data
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
4 %
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No sensitization reactions were observed.
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
4%
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No sensitization reactions were observed.
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: not sensitising
Conclusions:
Non-sensitising effects were known in maximisation study of test chemical exposed to 25 human volunteers.
Executive summary:

Maximization test was conducted on 25 human volunteers to determine skin sensitization potential of test chemical.

 

The test chemical in petrolatum was applied on the skin of 25 healthy male patients. Application was under occlusion to the same site on the forearm of all subjects for five alternate day, 48 h periods. The patch sites were pretreated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. Following a 10 day rest period, challenge patches were applied to fresh sites on the back for 48 h under occlusion. The challenge site was pretreated for 1 h with 10% SLS. The challenge site was evaluated at 48 and 72 h.

 

Since Non-sensitizing effects were known in maximization test, the test chemical was considered to be non-sensitizing on human skin.

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;

 

Maximization test was conducted on 25 human volunteers to determine skin sensitization potential of test chemical. The test chemical in petrolatum was applied on the skin of 25 healthy male patients. Application was under occlusion to the same site on the forearm of all subjects for five alternate day, 48 h periods. The patch sites were pretreated for 24 h with 5% aqueous sodium lauryl sulfate (SLS) under occlusion. Following a 10 day rest period, challenge patches were applied to fresh sites on the back for 48 h under occlusion. The challenge site was pretreated for 1 h with 10% SLS. The challenge site was evaluated at 48 and 72 h. Since Non-sensitizing effects were known in maximization test, the test chemical was considered to be non-sensitizing on human skin.

 

Another maximization test was carried out on 25 male volunteers, the test chemical was tested at a 4% concentration in petrolatum (2760µg/cm2) and the male volunteers were then observed for any cutaneous reaction. Since none of the volunteers developed any skin reaction, the test chemical was considered to be not sensitizing on human skin.

 

The above results were further supported by maximization test carried out for test chemical on 25 human volunteersto determine the sensitization potential of test substance.Thetest substancewas tested at a 4 % concentration in petrolatum. The test material did not produce any sensitization reaction in treated 25 human subjects. Thereforethe test chemical was considered to be not sensitizing on human skin.

 

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

 

The overall result was further supported by the skin sensitization study conducted on guinea pigs by Magnusson and Kligman guinea pig maximization test for test chemical. Sensitization was induced in guinea pigs by intradermal injections of both tets substance and complete Freunds Adjuvant and the induction process supplemented 7 days later by test substance applied to the shoulder injection sites under occluded patch: further challenges were made at weekly intervals as required. As none of the treated guinea pigs had developed any signs of skin sensitization, the test chemical was considered as not sensitizing.

 

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.