Registration Dossier

Administrative data

Description of key information

Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin sensitization for (+)-Neomenthol was estimated to be not sensitizing  on guinea pig and humans. Thus it can be concluded that the substance, (+)-Neomenthol  has no skin sensitization effects.

Hence, (+)-Neomenthol can be considered to be not sensitizing to skin.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
data is from authoritative database
Reference:
Composition 0
Qualifier:
according to
Guideline:
other: Estimated data
Principles of method if other than guideline:
To estimate the allergenic potential of (+)-Neomenthol in guinea pigs and humans
GLP compliance:
not specified
Type of study:
other: Estimated data
Test material information:
Composition 1
Specific details on test material used for the study:
Name of the test chemical: (1S,2S,5R)-5-methyl-2-propan-2-ylcyclohexan-1-olCommon Name: (+)-NeomentholMolecular Formula: C10H20OMolecular Weight: 156.269 g/molSubstance Type: OrganicPhysical State: Solid
Species:
other: Guinea pigs and humans
Strain:
not specified
Sex:
not specified
Route:
other: not specified
Vehicle:
not specified
Adequacy of induction:
not specified
No.:
#1
Route:
other: not specified
Vehicle:
not specified
Adequacy of challenge:
not specified
No. of animals per dose:
No data available
Details on study design:
No data available
Challenge controls:
No data available
Positive control substance(s):
not specified
Concentration:
No data available
No. of animals per dose:
No data available
Reading:
1st reading
Group:
test group
Dose level:
No data available
Clinical observations:
No reactions observed
Remarks on result:
no indication of skin sensitisation

Table showing allergic dermatitis estimation by three different models i.e, Leadscope, battery and SciQSAR & CASE Ultra,the average results was given by the fourth model i.e, Battery model.

                                                               

 

Exp

Battery

CASE Ultra

Leadscope

SciQSAR

Allergic Contact Dermatitis in Guinea Pig and Human

 

 

NA

 

NEG_IN

 

NEG_IN

 

NEG_IN

 

NEG_IN

                                                                      

Where,

IN = inside applicability domain, NEG = Negative; INC = Inconclusive; POS = Positive, OUT = outside applicability domain

 

Interpretation of results:
other: not sensitizing
Conclusions:
Based on the QSAR prediction done using the Danish (Q)SAR Database, the skin sensitization for (+)-Neomenthol was estimated to be not sensitizing on guinea pig and humans. Thus it can be concluded that the substance, (+)-Neomenthol has no skin sensitization effects.Hence, (+)-Neomenthol can be considered to be not sensitizing to skin.
Executive summary:

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for (+)-Neomenthol. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, (+)-Neomentholwas considered to be not sensitizing.

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

Various studies have been summarized to ascertain the degree of skin sensitization caused by (+)-Neomenthol in living organisms. These studies include in vivo experiments on guinea pigs and humans for the target chemical and structurally similar chemicals. The experimental results have been also been compared with the estimated results.

Skin sensitization effects were estimated by four different models i.e, Battery, Leadscope, SciQSAR and CASE Ultra used within Danish QSAR database for (+)-Neomenthol. Based on estimation, no skin sensitization reactions were observed in guinea pigs and humans. Therefore, (+)-Neomenthol was considered to be not sensitizing.

This is supported by the results of an Open Epicutaneous test was conducted in guinea pigs (male and female) to determine the skin sensitization potential of the structurally similar chemicals.

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 day 1 during induction, 0.1 ml of undiluted test chemical was applied 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.

Both of the structurally similar chemicals failed to induce dermal sensitization reactions in guinea pigs after the challenge exposure. Hence, they can be considered to be not sensitizing.

Based on the results from the available studies for the target as well as structurally similar chemical, and applying the weight of evidence approach, (+)-Neomenthol can be considered to be not sensitizing to skin.

 

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the available studies for the target chemical as well its structurally similar chemicals, (+)-Neomenthol can be considered to be not sensitizing to skin.

It can be classified under the category “Not Classified” as per CLP regulation.