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Description of key information

The skin sensitization potential of test chemical was assessed in various experimental studies conducted on human subjects. The predicted data using the Danish QSAR database has also been compared with the experimental data. Based on the available data for the test chemical and supporting studies, it can be concluded that the test chemical is not able to cause skin sensitization and thus can be considered asnon-skin sensitizer. 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 publication
Qualifier:
according to
Guideline:
other: as mentioned below
Principles of method if other than guideline:
To determine skin sensitization potential of test chemical in human using maximization test
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:
not specified
Sex:
not specified
Route:
other: no data
Vehicle:
petrolatum
Concentration / amount:
2%
Adequacy of induction:
other: no skin sensitization reactions
No.:
#1
Route:
other: no data
Vehicle:
petrolatum
Concentration / amount:
2 %
Adequacy of challenge:
other: no skin sensitization reactions
No. of animals per dose:
25
Details on study design:
no data
Challenge controls:
no data
Positive control substance(s):
not specified
Reading:
1st reading
Group:
test group
Dose level:
2%
No. with + reactions:
0
Total no. in group:
25
Remarks on result:
other: no sensitization reactions.
Interpretation of results:
other: not sensitising
Conclusions:
Since the test chemical did not cause any known signs of contact sensitization, it was considered as not sensitizing to human skin.
Executive summary:

Maximization test was performed in 25 human subjects to assess the skin sensitization potential of test chemical. The test chemical was applied dermally to the skin of human volunteers at a dose of 2% in petrolatum. Since the test chemical did not cause any known signs of contact sensitization, it was considered as not sensitizing to human skin.

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

Various studies has 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 human and guinea pigs for test chemical .The predicted data using the Danish QSAR database has also been compared with the experimental data and summarized as below:

Maximization test was performed in 25 human subjects to assess the skin sensitization potential of test chemical. The test chemical was applied dermally to the skin of human volunteers at a dose of 2% in petrolatum. Since the test chemical did not cause any known signs of contact sensitization, it was considered as not sensitizing to 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.

Further, Test chemical was tested in a modified Draize test with groups of 10 male and female Hartley guinea pigs. After an induction time of 14 days, the challenge treatment consisted of an intradermal injection in one flank and topical application (uncovered) on the other flank with an application challenge concentration (ACC) of 20 %. Reactions were scored 24 hrs later. In the absence of sensitization reactions at first challenge, the induction and challenge procedures were repeated, but this time a confirmatory challenge with controls was included. At each challenge 4 previously untreated animals of the same sex and similar weight to the test animals were treated intradermally. Test chemical was assessed as non-sensitiser.

The above studies were furthermore supported by 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 overall results were further supported by skin sensitization study of chemical was conducted in 10 Hartley albino guinea pigs to determine its sensitization potential by using Modified Draize Technique.The preliminary irritation tests were performed in 8 guinea pigs to determine concentrations suitable for sensitization test [injection challenge concentration(ICC) and application challenge concentration(ACC).As a result of the preliminary studies, the concentration selected for skin sensitization test were 0.25% forICC and 20% for ACC.During the induction phase,the total dose was administered on one occasion as 4 intradermal injections, each 2.5 times the ICC (2.5X 0.25%). Fourteen days later each animal was challenged intradermally in one flank and topically in the other with 0.1 ml aliquots of test substance at the respective ICC and ACC (0.25 and 20 respectively). Twenty-four hours later the reactions were observed.In the absence of sensitization reactions at first challenge the induction and challenge procedures were repeated, andapparent sensitization reactions confirmed 7 days later by a second and confirmatory challenge with controls included.At 24 hours after the first challenge and at the second and confirmatory challengewith 0.25% and 20%test chemical,none of the rabbits showed positive results. Thus, it can be concluded that the test chemicalwas considered to be not sensitizing onguinea pigs.

Based on the above summarized studies for target chemical and its structurally 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 structurally and 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.