Tetrahydro-4-methyl-2H-pyran

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation, other

Remarks:

QSAR analysis

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

n/a

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. OECD Toolbox

2. OECD Toolbox (v. 3.4.0.17)

3. Input into model via CAS number / SMILES

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
Workflow:
Profiling the structure ofMTHP (Tetrahydro-4-methyl-2H-pyran) from the chemical databases in the Toolbox produced positive results for:
- Aquatic toxicity classification by ECOSAR (primary grouping)
The following categories were therefore formed using this information

Mechanistic:
- Protein binding by OASIS v1.4
- Protein binding by OECD
- Protein binding potency

Sub-categorization
- Protein binding by OASIS v1.4
- Chemical elements (subcategorization)
- Similarity boundary


Organic function group similarity and protein binding categories were then combined to give a category that was both structurally and mechanistically similar so as to increase the robustness of the estimations, resulting in the group of 49 analogues.


5. APPLICABILITY DOMAIN
The target chemical, scopolamine met the applicability domain used to provide a read-across estimation

The applicability domain is defined by following scheme
a) Referential boundary:
The target chemical should be classified as No alert found by Protein binding by OASIS v1.4

b) Referential boundary:
The target chemical should be classified as Bioavailable by Lipinski Rule Oasis ONLY

c) Similarity boundary:
Target: CC1CCOCC1
Threshold=30%,
Dice(Atom centered fragments)
Atom type; Count H attached; Hybridization

d) Parametric boundary:
The target chemical should have a value of log Kow which is >= 1.13

e) Parametric boundary:
The target chemical should have a value of log Kow which is <= 1.89

6. ADEQUACY OF THE RESULT
The prediction is based on 7 neighbours' values, 7 of them equal to prediction.
Prediction confidence is measured by the p-value = 7.81E-03 (strong confidence)

Data source

Reference

Reference Type:

other: Expert statement/QSAR

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

QSAR analysis

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetrahydro-4-methyl-2H-pyran

EC Number:

225-207-5

EC Name:

Tetrahydro-4-methyl-2H-pyran

Cas Number:

4717-96-8

Molecular formula:

C6H12O

IUPAC Name:

4-methyltetrahydro-2H-pyran

Test material form:

liquid

Specific details on test material used for the study:

Refer to report 0312880-TOX4 attached

In vivo test system

Test animals

Details on test animals and environmental conditions:

n/a

Results and discussion

Positive control results:

n/a

In vitro / in chemico

Results

Parameter:

other:

Remarks:

QSAR OECD Toolbox analysis undertaken

Vehicle controls validity:

not examined

Negative controls validity:

not examined

Positive controls validity:

not examined

Remarks on result:

positive indication of skin sensitisation

Other effects / acceptance of results:

n/a

In vivo (LLNA)

Cellular proliferation data / Observations:

n/a

Any other information on results incl. tables

n/a

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Conclusions:

It is recognised that corrosive properties do not preclude performing in silico assessments. For this reason, in silico assessment using the OECD Toolbox has been undertaken to assess the relevant data available for MTHP and similar chemicals.

In conclusion, the in silico estimates from the OECD Toolbox indicates that MTHP is predicted to be a devoid of skin sensitization potential based on protein binding, deemed to be an applicable domain. No further work is considered necessary in addressing this endpoint. Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP has no obligatory labelling requirement for skin sensitization and is unclassified for this endpoint, however MTHP is classified as skin corrosion (Category 1A).

Executive summary:

It is recognised that corrosive properties do not preclude performing in silico assessments. For this reason, in silico assessment using the OECD Toolbox has been undertaken to assess the relevant data available for MTHP and similar chemicals.  

In conclusion, the in silico estimates from the OECD Toolbox indicates that MTHP is predicted to be a devoid of skin sensitization potential based on protein binding, deemed to be an applicable domain. No further work is considered necessary in addressing this endpoint. Therefore, according to Annex I for Regulation (EC) 1272/2008 the active ingredient, MTHP has no obligatory labelling requirement for skin sensitization and is unclassified for this endpoint, however MTHP is classified as skin corrosion (Category 1A).