Benzyl isovalerate

Endpoint summary

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)

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

Justification for type of information:

Data is from collection of data .

Qualifier:

according to guideline

Guideline:

other: As mentioed below

Principles of method if other than guideline:

To evaluate the skin sensitizing potential of test chemical in human by human maximization test.

GLP compliance:

not specified

Type of study:

other: human maximization test .

Justification for non-LLNA method:

Sufficient for classification .

Species:

other: Human

Strain:

other:

Remarks:

Not applicable

Sex:

not specified

Details on test animals and environmental conditions:

No data available.

Route:

other: No data

Vehicle:

petrolatum

Concentration / amount:

4%

Route:

other: No data available

Vehicle:

petrolatum

Concentration / amount:

4%

No. of animals per dose:

25 human volunteers

Details on study design:

No data available.

Challenge controls:

No data available.

Positive control substance(s):

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

4%

No. with + reactions:

0

Total no. in group:

25

Clinical observations:

No sensitization was observed

Remarks on result:

no indication of skin sensitisation

The test material was not sensitizing.

Interpretation of results:

other: Not sensitizing

Conclusions:

There was no indication of sensitization in any of 25 human volunteer’s .Therefore the test chemical was considered to be non-sensitizing to the human skin.

Executive summary:

A skin sensitization test for test chemical was observed in 25 human volunteers by Human maximization test. The test chemical was tested at a 4% concentration in petrolatum on 25 human volunteers. There was no indication of sensitization in any of 25 human volunteer’s .Therefore the test chemical was considered to be non-sensitizing to the 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 substances.The predicted data usingDanish QSAR databasethe has also been compared with the experimental data and summarized as below;

 

A maximization test was carried out on 25 human volunteers to assess the dermal sensitization potential of test chemical. The test chemical was applied to the skin of human volunteers at a dose of 4% in petrolatum and observed for effects (duration not specified). The chemical neither caused any dermal reactions nor dermal sensitizing effects. Hence, the test chemical can be considered as not sensitizing to 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 above results were supported byAn Open Epicutaneous Test (OET) performed on guinea pigs to assess the skin sensitization potential of similar 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 2 %. On day 1 during induction, 0.1 ml of the test chemical was applied at concentrations of 2% 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 2%.Thus the chemical was considered to be not sensitizing on skin of guinea pigs at concentration of 2% in an Open Epicutaneous Test (OET).

 

The overall results were further supported by anothermaximization testperformed for similar read across chemical. The test chemical was tested at 4% (2760µg/cm2) in petrolatum on 25 healthy male patients. Application was under occlusion to the same site on the forearms 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. No sensitization reactions were observed. Hence, the test chemical can be considered to be not sensitizing to the skin of 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 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.