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Description of key information

The available data for this endpoint include two human studies and QSARs conducted with OECD Toolbox and VEGA software.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
Human volunteer study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
05 June 1974
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Maximization test in human volunteers
- Short description of test conditions: Twenty five subjects were exposed to the test item for 24 hours.
- Parameters analysed / observed: No details reported.
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
No details reported.
Specific details on test material used for the study:
No details reported.
Species:
other: Twenty five healthy adult human volunteers
Strain:
other: Not applicable
Sex:
male/female
Details on test animals and environmental conditions:
No details reported.
Positive control results:
No details reported.
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Not reported
No. with + reactions:
1
Total no. in group:
25
Clinical observations:
One case of sensitization was observed out of the 25 subjects. No further details reported.
Remarks on result:
other: Questionable sensitizer
Key result
Reading:
1st reading
Hours after challenge:
0
Group:
test chemical
Dose level:
Not reported
No. with + reactions:
1
Total no. in group:
25
Clinical observations:
One case of sensitization was observed out of the 25 subjects. No further details reported.
Remarks on result:
other: Questionable sensitizer

The test item produced 1 case of sensitization to a degree of 1 + (no details on the scoring system were reported). The remaining 24 volunteers did not produce a response to the test item. The author reports that the test item should be considered as a 'questionable sensitiser'.

Interpretation of results:
GHS criteria not met
Conclusions:
The test item produced 1 case of sensitization to a degree of 1 + (no details on the scoring system were reported). The remaining 24 volunteers did not produce a response to the test item. The author reports that the test item should be considered as a 'questionable sensitiser'.
Executive summary:

The test item produced 1 case of sensitization to a degree of 1 + (no details on the scoring system were reported). The remaining 24 volunteers did not produce a response to the test item. The author reports that the test item should be considered as a 'questionable sensitiser'.

Endpoint:
skin sensitisation, other
Remarks:
Human volunteer study
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
21 August 1974
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Qualifier:
no guideline followed
Principles of method if other than guideline:
- Principle of test: Maximization test in human volunteers
- Short description of test conditions: Twenty five subjects were exposed to the test item for 24 hours.
- Parameters analysed / observed: No details reported.
GLP compliance:
no
Type of study:
patch test
Justification for non-LLNA method:
No details reported.
Specific details on test material used for the study:
No details reported.
Species:
other: Twenty five healthy adult human volunteers
Strain:
other: Not applicable
Sex:
not specified
Details on test animals and environmental conditions:
No details reported.
Positive control results:
No details reported.
Key result
Reading:
2nd reading
Hours after challenge:
24
Group:
test chemical
Dose level:
Not reported
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No details reported.
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
0
Group:
test chemical
Dose level:
Not reported
No. with + reactions:
0
Total no. in group:
25
Clinical observations:
No details reported
Remarks on result:
no indication of skin sensitisation

There were no instances of contact-sensitization from the test item. The author reports that it is 'unlikely' that the test item would present a danger of contact-sensitization in normal, intended use.

Interpretation of results:
GHS criteria not met
Conclusions:
There were no instances of contact-sensitization from the test item. The author reports that it is 'unlikely' that the test item would present a danger of contact-sensitization in normal, intended use.
Executive summary:

There were no instances of contact-sensitization from the test item. The author reports that it is 'unlikely' that the test item would present a danger of contact-sensitization in normal, intended use.

Endpoint:
skin sensitisation, other
Type of information:
(Q)SAR
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, and documentation / justification is limited
Justification for type of information:
1. SOFTWARE : OECD Toolbox

2. MODEL (incl. version number) : V4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :CCCc1ccc(OC)cc1 and CAS RN: 104-45-0

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Sensitisation
- Unambiguous algorithm: Read across analysis; takes the highest mode value from the nearest 5 neighbours
- Defined domain of applicability: Prediction is within the domain ranges.
- Appropriate measures of goodness-of-fit and robustness and predictivity: The prediction is based on 6 values, 5 of them (83.3%) equal to predicted value. Prediction confidence is measured by the p-value: 0.109
- Mechanistic Interpretation: Protein binding for skin sensitisation is assessed using the 'Protein binding alerts for skin sensitistation by OASIS' profile. Any structures with alerts that did not match the target chemical were excluded from the prediction.

5. APPLICABILITY DOMAIN
- Descriptor domain: Protein binding alerts for skin sensitization by OASIS
- Structural and mechanistic domains: Protein binding by OASIS, substance type, chemical elements, structure similarity
- Similarity with analogues in the training set: See attached OECD Toolbox prediction report format for further details.


6. ADEQUACY OF THE RESULT
Read Across prediction for skin sensitisation based on 6 values, 5 of them (83.3%) equal to predicted value. Predicted: Negative. Prediction confidence is measured by the p-value: 0.109
Guideline:
other: REACH Guidance on QSARs R.6
Specific details on test material used for the study:
SMILES: CCCc1ccc(OC)cc1
Interpretation of results:
GHS criteria not met
Conclusions:
The OECD Toolbox software prediction for skin sensitisation is 'negative'. This is based on 6 values, 5 of them (83.3%) equal to predicted value. The prediction confidence is measured by the p-value: 0.109
Executive summary:

The OECD Toolbox software prediction for skin sensitisation is 'negative'. This is based on 6 values, 5 of them (83.3%) equal to predicted value. The prediction confidence is measured by the p-value: 0.109

Endpoint:
skin sensitisation, other
Type of information:
(Q)SAR
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, and documentation / justification is limited
Justification for type of information:
1. SOFTWARE : OECD Toolbox

2. MODEL (incl. version number) : V4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :CCCc1ccc(OC)cc1 and CAS RN: 104-45-0

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Sensitisation
- Unambiguous algorithm: Read across analysis; takes the highest mode value from the nearest 5 neighbours
- Defined domain of applicability: Prediction is within the domain ranges.
- Appropriate measures of goodness-of-fit and robustness and predictivity: The prediction is based on 6 values, 5 of them (83.3%) equal to predicted value
Prediction confidence is measured by the p-value: 3.25E-11
- Mechanistic Interpretation: Protein binding for skin sensitisation is assessed using the 'Protein binding alerts for skin sensitistation by OASIS' profile. Any structures with alerts that did not match the target chemical were excluded from the prediction.

5. APPLICABILITY DOMAIN
- Descriptor domain: Protein binding alerts for skin sensitization by OASIS
- Structural and mechanistic domains: Protein binding by OASIS, substance type, chemical elements, structure similarity
- Similarity with analogues in the training set: See attached OECD Toolbox prediction report format for further details.


6. ADEQUACY OF THE RESULT
Read Across prediction for skin sensitisation based on 6 values, 5 of them (83.3%) equal to predicted value Predicted: Negative. Prediction confidence is measured by the p-value: 3.25E-11
Guideline:
other: REACH Guidance on QSARs R.6
Specific details on test material used for the study:
SMILES: CCCc1ccc(OC)cc1
Interpretation of results:
GHS criteria not met
Conclusions:
The OECD Toolbox software prediction for skin sensitisation is 'negative'. This is based on 6 values, 5 of them (83.3%) equal to predicted value. The prediction confidence is measured by the p-value: 3.25E-11
Executive summary:

The OECD Toolbox software prediction for skin sensitisation is 'negative'. This is based on 6 values, 5 of them (83.3%) equal to predicted value. The prediction confidence is measured by the p-value: 3.25E-11

Endpoint:
skin sensitisation, other
Type of information:
(Q)SAR
Adequacy of study:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, and documentation / justification is limited
Justification for type of information:
1. SOFTWARE : OECD Toolbox

2. MODEL (incl. version number) : V4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :CCCc1ccc(OC)cc1 and CAS RN: 104-45-0

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: EC3
- Unambiguous algorithm: Read across analysis; takes the highest mode value from the nearest 5 neighbours
- Defined domain of applicability: Prediction is within the domain ranges.
- Appropriate measures of goodness-of-fit and robustness and predictivity: The prediction is based on 6 values, 5 of them (83.3%) equal to predicted value. Prediction confidence is measured by the p-value: 0.109
- Mechanistic Interpretation: Protein binding for skin sensitisation is assessed using the 'Protein binding alerts for skin sensitistation by OASIS' profile. Any structures with alerts that did not match the target chemical were excluded from the prediction.

5. APPLICABILITY DOMAIN
- Descriptor domain: Protein binding alerts for skin sensitization by OASIS
- Structural and mechanistic domains: Protein binding by OASIS, substance type, chemical elements, structure similarity
- Similarity with analogues in the training set: See attached OECD Toolbox prediction report format for further details.


6. ADEQUACY OF THE RESULT
Read Across prediction for skin sensitisation based on 6 values, 5 of them (83.3%) equal to predicted value. Predicted: Postive. Prediction confidence is measured by the p-value: 0.109
Guideline:
other: REACH Guidance on QSARs R.6
Specific details on test material used for the study:
SMILES: CCCc1ccc(OC)cc1
Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
The OECD Toolbox software prediction for EC3 is 'postive'. This is based on 6 values, 5 of them (83.3%) equal to predicted value. The prediction confidence is measured by the p-value: 0.109
Executive summary:

The OECD Toolbox software prediction for EC3 is 'postive'. This is based on 6 values, 5 of them (83.3%) equal to predicted value. The prediction confidence is measured by the p-value: 0.109

Endpoint:
skin sensitisation, other
Type of information:
(Q)SAR
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
Justification for type of information:
1. SOFTWARE: VEGA QSAR MODEL Core version 1.2.4

2. MODEL: Mutagenicity (Ames test) model (CAESAR) 2.1.16

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
:O(c1ccc(cc1)CCC)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Skin sensitisation
- Unambiguous algorithm: No details reported.
- Defined domain of applicability: Compound is into the Applicability Domain of the model
- Appropriate measures of goodness-of-fit and robustness and predictivity:
Good reliability


5. APPLICABILITY DOMAIN
- Descriptor domain:Global AD Index = 0.957
- Similarity with analogues in the training set:Strongly similar


6. ADEQUACY OF THE RESULT
The model is considered reliable.

A QSAR conducted using VEGA software and applying the CAESAR method results in a 'sensitising' result.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
A QSAR conducted using VEGA software and applying the CAESAR method results in a 'sensitising' result.
Executive summary:

A QSAR conducted using VEGA software and applying the CAESAR method results in a 'sensitising' result.

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

Justification for classification or non-classification

The test item was negative for sesnsitisation in two human patch tests. QSAR predictions for sensitisation are equivocal; of the three predictions from OECD toolbox, two are considered to be negative (Buehler test prediction) and one is conisdered to be postive (LLNA prediction). A QSAR conducted using VEGA software has a 'sensitising' result.

Therefore, considering all of the available data (negative human patch tests and overall equivocal QSAR predictions), the test item is not classificable for sensitisation according to CLP criteria (EC Regulation 1272/2008).