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EC number: 203-203-4 | CAS number: 104-45-0
Endpoint summary
Administrative data
Description of key information
Data for skin irritation includes two human volunteer studies and three QSAR predictions. The QSARs include predictions using ToxTree software as well as a read-across and trend analysis prediction using OECD Toolbox.
Data for eye irritation includes a read-across and trend analysis prediction using OECD Toolbox.
Key value for chemical safety assessment
Skin irritation / corrosion
Link to relevant study records
- Endpoint:
- skin irritation / corrosion, 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:
Skin irritation study in human volunteers as a 'pre-test' for a skin sensitization study.
- Short description of test conditions: Five subjects were exposed to the test item for 48 hours.
- Parameters analysed / observed: No details reported. - GLP compliance:
- no
- Specific details on test material used for the study:
- No details reported.
- Species:
- other: Human volunteers
- Strain:
- other: Not applicable
- Details on test animals or test system and environmental conditions:
- No details on the test subjects were reported.
- Type of coverage:
- occlusive
- Preparation of test site:
- not specified
- Vehicle:
- not specified
- Controls:
- no
- Amount / concentration applied:
- No details reported.
- Duration of treatment / exposure:
- 48 hours
- Observation period:
- No details reported.
- Number of animals:
- Five healthy adult volunteers.
- Details on study design:
- No details reported.
- Irritation parameter:
- other: Not specified
- Basis:
- other: Not specified
- Time point:
- other: Not specified
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- No subject had any irritation from the test item. No further details reported.
- Other effects:
- No further details reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- A patch of the test item was applied to the normal sites on the backs of five human volunteers for 48 hours under occlusion. No subject had any irritation from the test item.
- Executive summary:
A patch of the test item was applied to the normal sites on the backs of five human volunteers for 48 hours under occlusion. No subject had any irritation from the test item.
The test substance was not considered to be irritating under test conditions, according to CLP criteria (EC Regulation 1272/2008).
- Endpoint:
- skin irritation / corrosion, 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:
Skin irritation study in human volunteers as a 'pre-test' for a skin sensitization study.
- Short description of test conditions: Five subjects were exposed to the test item for 48 hours.
- Parameters analysed / observed: No details reported. - GLP compliance:
- no
- Specific details on test material used for the study:
- No details reported.
- Species:
- other: Human volunteers
- Strain:
- other: Not applicable
- Details on test animals or test system and environmental conditions:
- No details on the test subjects were reported.
- Type of coverage:
- occlusive
- Preparation of test site:
- not specified
- Vehicle:
- not specified
- Controls:
- no
- Amount / concentration applied:
- No details reported.
- Duration of treatment / exposure:
- 48 hours
- Observation period:
- No details reported.
- Number of animals:
- Five healthy adult volunteers.
- Details on study design:
- No details reported.
- Irritation parameter:
- other: Not specified
- Basis:
- other: Not specified
- Time point:
- other: Not specified
- Reversibility:
- not specified
- Remarks on result:
- no indication of irritation
- Irritant / corrosive response data:
- No subject had any irritation from the test item. No further details reported.
- Other effects:
- No further details reported.
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- A patch of the test item was applied to the notmal sites on the backs of five human volunteers for 48 hours under occlusion. No subject had any irritation from the test item.
- Executive summary:
A patch of the test item was applied to the notmal sites on the backs of five human volunteers for 48 hours under occlusion. No subject had any irritation from the test item. The test substance was not considered to be irritating under test conditions, according to CLP criteria (EC Regulation 1272/2008).
- Endpoint:
- skin irritation / corrosion, other
- Remarks:
- In silico prediction
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- 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
- OECD QSAR Toolbox
2. MODEL- V4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCc1ccc(OC)cc1 and CAS: 104-45-0
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Human Health Hazards -> Irritation / Corrosion -> in Vitro -> Skin
- Unambiguous algorithm: takes the mode value from the nearest 5 neighbours
- Defined domain of applicability: PRedictions are within the domain
- Appropriate measures of goodness-of-fit and robustness and predictivity: The prediction is based on 5 values, 3 of them (60.0%) equal to predicted value
Prediction confidence is measured by the p-value: 1.87E-07
- Mechanistic interpretation: See attached QPRF for further details
5. APPLICABILITY DOMAIN
- Descriptor domain: - log Kow: from 2.73 to 4.17, Undefined Endpoint: not classified (x1); Category 2 (irritant) (x1); not irritating (x3)
- Structural and mechanistic domains: Inclusion rules by BfR, substance type, Exclusion rules by BfR, chemical elements, structure similarity
- Similarity with analogues in the training set: See attached QPRF for further details
6. ADEQUACY OF THE RESULT
Read across prediction for skin irritation; predicted: not irritating. This result is considered adequate. - Qualifier:
- according to guideline
- Guideline:
- other: REACH guidance on QSARs
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The OECD Toolbox software prediction for skin irritation is 'not irritating'. This is based on 5 values, 3 of them (60.0%) equal to predicted value. The prediction confidence is measured by the p-value: 1.87E-07.
- Executive summary:
The OECD Toolbox software prediction for skin irritation is 'not irritating'. This is based on 5 values, 3 of them (60.0%) equal to predicted value. The prediction confidence is measured by the p-value: 1.87E-07.
- Endpoint:
- skin irritation / corrosion, other
- Remarks:
- In silico prediction
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- Reliability:
- 4 (not assignable)
- Rationale for reliability incl. deficiencies:
- results derived from a (Q)SAR model, with limited documentation / justification
- Justification for type of information:
- 1. SOFTWARE
- OECD QSAR Toolbox
2. MODEL- V4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCc1ccc(OC)cc1 and CAS: 104-45-0
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Human Health Hazards -> Irritation / Corrosion -> in Vitro -> Skin
- Unambiguous algorithm: Linear approximation: Primary Irritation Index = 1.67 (±3.60) -0.336 (±1.61) * log Kow,
- Defined domain of applicability:
Predictions are not in the domain
- Appropriate measures of goodness-of-fit and robustness and predictivity:
The prediction is based on 5 values within range 0 - 1.68
Prediction confidence range (0.95%): ± 4.08
- Mechanistic interpretation:
See attached QPRF for further details
5. APPLICABILITY DOMAIN
- Descriptor domain:
- log Kow: from 1.08 to 3.21 Primary Irritation Index: from 0 to 1.68
- Structural and mechanistic domains:
Inclusion rules by BfR, substance type, Exclusion rules by BfR, chemical elements, structure similarity
- Similarity with analogues in the training set:
See attached QPRF for further details
6. ADEQUACY OF THE RESULT
Trend analysis prediction for skin irritation; predicted value: 0.464. - Qualifier:
- according to guideline
- Guideline:
- other: REACH guidance on QSARs
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The OECD Toolbox software prediction for Primary Irritation Index is '0.464'. This is based on 5 values within the range of 0 -168 (confidence range (0.95%): ± 4.08).
- Executive summary:
The OECD Toolbox software prediction for Primary Irritation Index is '0.464'. This is based on 5 values within the range of 0 -168 (confidence range (0.95%): ± 4.08).
- Endpoint:
- skin irritation / corrosion, other
- Remarks:
- In silico prediction
- Type of information:
- (Q)SAR
- Adequacy of study:
- other information
- Study period:
- Not applicable
- Justification for type of information:
- 1. SOFTWARE : ToxTree (Estimation of Toxic Hazard- A Decision Tree Approach)
2. MODEL: v.2.6.13
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL: CCC\C=C\C=O
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Skin Irritation/skin corrosion decsion tree method. A decision tree for estimating skin irritation and corrosion potential based on rules published in "The Skin Irritation Corrosion Rules Estimation Tool (SICRET), John D. Walker, Ingrid Gerner, Etje Hulzebos, Kerstin Schlegel, QSAR Comb. Sci. 2005, 24, pp. 378-384"
- Unambiguous algorithm: A decision tree approach is applied within ToxTree to identify structural alerts.
- Defined domain of applicability: No details on how the substance falls within the applicability domain of the model was provided by the software.
- Appropriate measures of goodness-of-fit and robustness and predictivity: None provided within the model.
5. APPLICABILITY DOMAIN
No details on how the substance falls within the applicability domain of the model was provided by the software.
6. ADEQUACY OF THE RESULT
No details on how the prediction fits the purpose of classification and labelling and/or risk assessment was provided by the software. - Guideline:
- other: REACH Guidance on QSARs R.6
- Specific details on test material used for the study:
- SMILES: O(c1ccc(cc1)CCC)C
- Irritation / corrosion parameter:
- other: Irritating or corrosive to the skin based on 'Group C, CHO (Q4)' and 'ethylene glycol ethers (Q53)' structural alerts
- Vehicle controls validity:
- not applicable
- Negative controls validity:
- not applicable
- Positive controls validity:
- not applicable
- Remarks on result:
- positive indication of irritation
- Interpretation of results:
- Category 2 (irritant) based on GHS criteria
- Conclusions:
- The in silico ToxTree software using the 'Skin irritation/skin corrosion' decision tree predictes the test item to be 'irritating or corrosive to the skin' based on 'Group C, CHO (Q4) and 'ethylene glycol ethers (Q53)' structural alerts.
- Executive summary:
- The in silico ToxTree software using the 'Skin irritation/skin corrosion' decision tree predictes the test item to be 'irritating or corrosive to the skin' based on 'Group C, CHO (Q4) and 'ethylene glycol ethers (Q53)' structural alerts.
Referenceopen allclose all
The OECD Toolbox software prediction for skin irritation is 'not irritating'. This is based on 5 values, 3 of them (60.0%) equal to predicted value. The prediction confidence is measured by the p-value: 1.87E-07.
The OECD Toolbox software prediction for Primary Irritation Index is '0.464'. This is based on 5 values within the range of 0 -168 (confidence range (0.95%): ± 4.08).
The in silico ToxTree software using the 'Skin irritation/skin corrosion' decision tree predictes the test item to be 'irritating or corrosive to the skin'.
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not irritating)
Eye irritation
Link to relevant study records
- Endpoint:
- eye irritation: in vitro / ex vivo
- Remarks:
- In silico prediction
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Study period:
- Not applicable
- 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
- OECD QSAR Toolbox
2. MODEL- V4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCc1ccc(OC)cc1 and CAS: 104-45-0
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Human Health Hazards -> Irritation / Corrosion -> in Vitro -> Eye
- Unambiguous algorithm:
takes the mode value from the nearest 5 neighbours
- Defined domain of applicability:
PRedictions are within the domain
- Appropriate measures of goodness-of-fit and robustness and predictivity:
The prediction is based on 6 values, 3 of them (60.0%) equal to predicted value
Prediction confidence is measured by the p-value: 3.13E-07
- Mechanistic interpretation:
See attached QPRF for further details
5. APPLICABILITY DOMAIN
- Descriptor domain:
- log Kow: from 3.01 to 4.3, Undefined Endpoint: highly irritating (x1); not classified (x1); slightly irritating (x1); not
irritating (x3)
- Structural and mechanistic domains:
Inclusion rules by BfR, substance type, Exclusion rules by BfR, chemical elements, structure similarity
- Similarity with analogues in the training set:
See attached QPRF for further details
6. ADEQUACY OF THE RESULT
Read across prediction for eye irritation; predicted: not irritating. This result is considered adequate. - Qualifier:
- according to guideline
- Guideline:
- other: REACH guidance on QSARs
- Irritation parameter:
- other: Overall prediction
- Run / experiment:
- No details reported.
- Vehicle controls validity:
- other: No details reported.
- Negative controls validity:
- other: No details reported.
- Positive controls validity:
- other: No details reported.
- Remarks on result:
- no indication of irritation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The OECD Toolbox software prediction for the predicted endpoint eye irritation has the predicted value of 'not irritating'. The prediction is based on 6 values, 3 of them (50.0%) equal to predicted value. Prediction confidence is measured by the p-value: 3.137E-07.
- Executive summary:
The OECD Toolbox software prediction for the predicted endpoint eye irritation has the predicted value of 'not irritating'. The prediction is based on 6 values, 3 of them (50.0%) equal to predicted value. Prediction confidence is measured by the p-value: 3.137E-07.
- Endpoint:
- eye irritation: in vivo
- Remarks:
- In silico prediction
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Study period:
- Not applicable
- 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
- OECD QSAR Toolbox
2. MODEL- V4.1
3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CCCc1ccc(OC)cc1 and CAS: 104-45-0
4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Human Health Hazards -> Irritation / Corrosion -> in Vitro -> eye
- Unambiguous algorithm: Linear approximation: MMAS = 46.3 (±21.4) -13.6 (±8.07) * log Kow,
- Defined domain of applicability:
Predictions are not in the domain
- Appropriate measures of goodness-of-fit and robustness and predictivity:
The prediction is based on 11 values within range 0.7 - 68.7
Prediction confidence range (0.95%): ± 34.2
- Mechanistic interpretation:
See attached QPRF for further details
5. APPLICABILITY DOMAIN
- Descriptor domain: Eye Irritation in ECETOC
- log Kow: from 0.37 to 3.94MMAS: from 0.7 to 68.7
- Structural and mechanistic domains:
Inclusion rules by BfR, substance type, Exclusion rules by BfR, chemical elements, structure similarity
- Similarity with analogues in the training set:
See attached QPRF for further details
6. ADEQUACY OF THE RESULT
Trend analysis prediction for eye irritation; predicted value: -2.55. - Qualifier:
- according to guideline
- Guideline:
- other: REACH guidance on QSARS
- Irritation parameter:
- other: MMAS
- Basis:
- other: Overall prediction
- Time point:
- other: No details reported
- Score:
- -2.55
- Reversibility:
- other: No details reported.
- Remarks on result:
- no indication of irritation
- Interpretation of results:
- GHS criteria not met
- Conclusions:
- The OECD Toolbox software prediction for the predicted endpoint MMAS has the predicted value of '-2.55'. The prediction is based on 13 values within the range of 0.7 -68.7 (confidence range (0.95%): ± 34.2).
- Executive summary:
The OECD Toolbox software prediction for the predicted endpoint MMAS has the predicted value of '-2.55'. The prediction is based on 13 values within the range of 0.7 -68.7 (confidence range (0.95%): ± 34.2).
Referenceopen allclose all
The OECD Toolbox software prediction for the predicted endpoint eye irritation has the predicted value of 'not irritating'. The prediction is based on 6 values, 3 of them (50.0%) equal to predicted value. Prediction confidence is measured by the p-value: 3.137E-07.
The OECD Toolbox software prediction for the predicted endpoint MMAS has the predicted value of '-2.55'. The prediction is based on 13 values within the range of 0.7 -68.7 (confidence range (0.95%): ± 34.2).
Additional information
Justification for classification or non-classification
Of the three QSARs conducted for skin irritation, one (ToxTree) predicts the test item to be an irritant and two (OECDToolbox; read across and trend analysis) predict the test item to be non-irritating. Furthermore, the two human studies report no signs of irritation. Therefore, based on a weight of evidence approach, and interpretation of the human data, the test item is not considered to be a skin irritant according to CLP criteria (EC Regulation 1272/2008).
Both of the QSARs for eye irritation predict a non-irritating result. Therefore, based on a weight of evidence approach, the test item is not considered to be an eye irritant according to CLP criteria (EC Regulation 1272/2008).
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