Tetrahydro-4-methyl-2H-pyran

Endpoint summary

Description of key information

Skin Sensitisation

The test article, MTHP (Tetrahydro-4-methyl-2H-pyran) meets the criteria for classification for skin corrosivity from data generated from the EpiDerm in vitro irritation [1] and corrosivity [2] models. In accordance with the ECHA Chapter R.7a guidance [3], a waiver is requested as MTHP is classified as skin corrosion (Category 1) and therefore a skin sensitisation study to address this endpoint is not required. Consequently, the required standard information in Column 1 (in vitro/in chemico assessment) may be omitted. Based on the available skin irritation and skin corrosion data, it is scientifically robust to submit a waiver for the skin sensitisation endpoint as stated in the R.7a guidance for REACh.

 

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 assesses the relevant data available for MTHP and similar chemicals.

 

In conclusion, thein silicoestimates from the OECD Toolbox indicates thatMTHP 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).

 

Respiratory sensitisation

There are currently no validated animal tests that deal specifically with respiratory tract sensitisation, therefore this endpoint was not investigated.

 

References

1. Mochizuki, H. (2017).In vitroskin irritation study of MTHP using EpiDerm. Ina Research Inc., Nagano, Japan. Unpublished report No.: DK16294

2. Suzuki, M. (2017).In vitroskin corrosion test of MTHP using EpiDerm SCT (EPI-200). Chemicals Evaluation and Research Institute, Japan, Hita. Unpublished report No.: K10-0240

3. ECHA (European Chemicals Agency). Guidance on information requirements and chemical safety assessment. Chapter R.7a: Endpoint specific guidance. December 2016

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vitro

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the available information indicates that the substance should be classified for respiratory sensitisation or corrosivity

Reason / purpose for cross-reference:

data waiving: supporting information

Reference 3

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)

Qualifier:

no guideline available

Principles of method if other than guideline:

QSAR analysis

GLP compliance:

no

Specific details on test material used for the study:

Refer to report 0312880-TOX4 attached

Details on test animals and environmental conditions:

n/a

Positive control results:

n/a

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

Cellular proliferation data / Observations:

n/a

n/a

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).

Endpoint conclusion

Endpoint conclusion:

no study available

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Comparison with the CLP criteria

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).