trans-hex-2-enal

Endpoint summary

Description of key information

Data for the skin irritation endpoint is fulfilled by a weight of evidence appraoch using data from a human patch test, a single dose dermal toxicity study in rabbits and QSAR predictions using ToxTree and OECD Toolbox software.

Eye irritation has been waived, based on an irritatn classification for skin irritation.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Remarks:

Dermal toxicity study

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1973

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Dermal toxicity study
- Short description of test conditions: 4 rabbits/dose
- Parameters analysed / observed:Mortality, clinical observations, skin irriration

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 'Sample marking' number: 72-159
- Expiration date of the lot/batch: No details reported.
- Purity test date: No details reported.



STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
No details reported.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
No details reported.

Species:

rabbit

Strain:

not specified

Details on test animals or test system and environmental conditions:

No details reported.

Type of coverage:

not specified

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

no

Amount / concentration applied:

0.32, 0.64, 1.25 or 5.0 g/kg bw

Duration of treatment / exposure:

No details reported.

Observation period:

14 Days

Number of animals:

4 rabbits/dose

Details on study design:

TEST SITE
No details reported.

REMOVAL OF TEST SUBSTANCE
No details reported.

OBSERVATION TIME POINTS
No details reported.

SCORING SYSTEM:
No details reported.

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other:

Time point:

other: No details reported

Reversibility:

not specified

Remarks on result:

not determinable because of methodological limitations

Irritant / corrosive response data:

'Moderate redness and oedema' was observed in one rabbit at 0.64 g/kg (640 mg/kg bw). All other rabbits at this dose level and at higher doses died, therefore further results are not reported.
No signs of skin irritation were reported at 0.32 g/kg (320 mg/kg bw).

Other effects:

0.32 g/kg bw (320 mg/kg bw): pupillary constriction
0.64 gkg bw (640 mg/kg bw): pupillary constriction, salivation and opisthotonus
1.25 g/kg bw (1250 mg/kg bw): pupillary constriction, salivation and opisthotonus, lacrimation, convulsions
5.0 g/kg bw (5000 mg/kg bw): pupillary constriction, salivation and opisthotonus, lacrimation, convulsions

Interpretation of results:

study cannot be used for classification

Conclusions:

In an acute dermal toxicity study in rabbits, 'moderate redness and oedema' was observed in one rabbit at 0.64 g/kg (640 mg/kg bw). All other rabbits at this dose level and at higher doses died, therefore further results are not reported. No signs of skin irritation were reported at 0.32 g/kg (320 mg/kg bw).

Executive summary:

In an acute dermal toxicity study in rabbits, 'moderate redness and oedema' was observed in one rabbit at 0.64 g/kg (600 mg/kg bw). All other rabbits at this dose level and at higher doses died, therefore further results are not reported. No signs of skin irritation were reported at 0.32 g/kg (320 mg/kg bw).

Reference 2

Endpoint:

skin irritation / corrosion, other

Remarks:

Human volunteer study

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

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 (male)

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 male 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 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.

Reference 3

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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE : OECD Toolbox

2. MODEL: V4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : CCCC=CC=O and CAS RN: 6728-26-3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: In vivo skin irritation
- Unambiguous algorithm: Read-across analysis; model takes the 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 8 values, 4 of them (50.0%) equal to predicted value. Prediction confidence is measured by the p-value: 3.47E-09

5. APPLICABILITY DOMAIN
- Descriptor domain: Log Kow: from 0.6 to 2.29
- Structural and mechanistic domains: Skin irritation/corrosion Inclusion rules by BfR, 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 undefined endpoint, based on 8 values, 4 (50%) equal to the predicted value. Predicted: irritiating. The predicted confidence if p=3.47E-9

This endpoint study record is part of a weight of evidence approach comprising of QSAR predictions using ToxTree and OECDToolbox. Both data sources agree with the prediction that the test substance is an irritant.

Guideline:

other: REACH Guidance on QSARs R.6

Specific details on test material used for the study:

SMILES: CCCC=CC=O
CAS RN: 6728-26-3

Irritation parameter:

other: Qualitative QSAR prediction for in vivo irritation based on read-across

Basis:

other: Qualitative QSAR prediction based on read-across

Remarks on result:

positive indication of irritation

Remarks:

The prediction is based on 8 values, 4 of them (50.0%) equal to predicted value. Prediction confidence is measured by the p-value: 3.47E-09

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The OECD Toolbox software prediction for in vivo skin irritation is that the test substance is 'irritating'. This is based on 8 values, 4 of them (50.0%) equal to predicted value. The prediction confidence is measured by the p-value: 3.47E-09.

Executive summary:

The OECD Toolbox software prediction for in vivo skin irritation is that the test substance is 'irritating'. This is based on 8 values, 4 of them (50.0%) equal to predicted value. The prediction confidence is measured by the p-value: 3.47E-09.

Reference 4

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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE : OECD Toolbox

2. MODEL: V4.1

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : CCCC=CC=O and CAS RN: 6728-26-3

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
- Defined endpoint: Primary Irritation Index
- Unambiguous algorithm: Primary Irritation Index = 8.15 (±3.21) -1.24 (±1.09) * log Kow
- 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 within range 3.46 - 7.08. Prediction confidence range (0.95%): ± 2.75

The prediction is scientifically value. See attached OECD Toolbox prediction report format for further details.

5. APPLICABILITY DOMAIN
- Descriptor domain: log Kow 1.37 to 3.94
- Structural and mechanistic domains: Skin irritation/corrosion Inclusion rules by BfR, Chemical elements, Structure similarity
- Similarity with analogues in the training set: See attached OECD Toolbox prediction report format for further details.

Target chemical is in domain. See attached OECD Toolbox prediction report format for further details.

6. ADEQUACY OF THE RESULT
Trend analysis prediction for Primary Irritation Index. Predicted result: 6.19 (95 % confidence interval 3.44 to 8.95). The result is considered adequate.

This endpoint study record is part of a weight of evidence approach comprising of QSAR predictions using ToxTree and OECDToolbox. Both data sources agree with the prediction that the test substance is an irritant.

Guideline:

other: REACH Guidance on QSARs R.6

Specific details on test material used for the study:

SMILES: CCCC=CC=O
CAS RN: 6728-26-3

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

other: QSAR prediction based on trend analysis

Score:

6.19

Reversibility:

not specified

Remarks on result:

probability of severe irritation

The OECD Toolbox software prediction for in vivo primary irritation index is 6.19, with a 95% confidence range of 3.44 to 8.95. Therefore, the test material is classifiable as category 2 (irritant) based on GHS criteria.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The OECD Toolbox software prediction for in vivo primary irritation index is 6.19, with a 95 % confidence range of 3.44 to 8.95. Therefore, the test item is classifiable as category 2 (irritant) based on GHS criteria.

Executive summary:

The OECD Toolbox software prediction for in vivo primary irritation index is 6.19, with a 95 % confidence range of 3.44 to 8.95. Therefore, the test item is classifiable as category 2 (irritant) based on GHS criteria.

Reference 5

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 adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWAR: 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 decision 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.

This endpoint study record is part of a weight of evidence approach comprising of QSAR predictions using ToxTree and OECDToolbox. Both data sources agree with the prediction that the test substance is an irritant.

Guideline:

other: REACH Guidance on QSARs R.6

Specific details on test material used for the study:

SMILES: CCC\C=C\C=O

Irritation / corrosion parameter:

other: Irritating or corrosive to the skin' based on 'Group C, CHO (Q4)' and 'aldehyde (Q41)' structural alerts.

Vehicle controls validity:

not applicable

Negative controls validity:

not applicable

Positive controls validity:

not applicable

Remarks on result:

positive indication of irritation

The in silico ToxTree software prediction using the 'Skin irritation/skin corrosion' decision tree results in 'irritating or corrosive to the skin'.

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

The in silico ToxTree software prediction using the 'Skin irritation/skin corrosion' decision tree results in 'irritating or corrosive to the skin' based on 'Group C, CHO (Q4)' and 'aldehyde (Q41)' structural alerts.

Executive summary:

The in silico ToxTree software prediction using the 'Skin irritation/skin corrosion' decision tree results in 'irritating or corrosive to the skin' based on 'Group C, CHO (Q4)' and 'aldehyde (Q41)' structural alerts.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as skin irritation and the available information indicates that it should be classified as eye irritation (Category 2)

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No effect on irritation was observed in the human study, however this study is not considered to be reliable (reliability score = 4) as only a small number of volunteers were used. In a single dose dermal toxicity study in rabbits, moderate redness and oedema was reported, which is indicative of an irritant effect. However, this study has also been given a reliability score of 4 as reversibility was not included as part of the study design. Qualitative QSAR modelling using ToxTree and OECD Toolbox predict the test substance to be 'irritant'; furthermore, a trend analysis QSAR prediction using OECD Toolbox gives a primary dermal irritation index score of 6.19. Therefore, the test item is classified as a Category 2 Skin Irritant (H315) according to CLP criteria (EC Regulation 1272/2008).

Based on the irritant classification for skin irritation, the endpoint, eye irritation has been waived in accordance with column 2 of REACH Annex VII.