Oct-7-enal

Endpoint summary

Description of key information

Skin Sensitisation

QSAR analysis using the OECD Toolbox (v. 3.4.0.17) was undertaken to provide a weight of evidence to for skin sensitisation potential of oct-7 -enal (7 -OEL). Visual inspection of the data in this category showed it to be relevant and robust. This was then used in the read-across approach taking the highest mode values from the 5 nearest neighbours with structural similarity to 7-OEL to provide the estimate that 7-OEL is predicted to be positive for skin sensitization potential via the likely mechanism of protein binding. The structures of the 5 nearest neighbours are all are short to medium chain monoaldehydes with a single unsaturated bond and log Kow values bracketing that of 7-OEL. Thus it was concluded that the target chemical, 7-OEL met the applicability domain used to provide a read-across estimation. In conclusion, the in silico estimates from the OECD Toolbox indicates that 7-OEL is predicted to be a skin sensitizer based on protein binding, deemed to be an applicable domain. As protein binding provides the highest predictive power in correctly identifying potential skin sensitisers, no further work is considered necessary in addressing this endpoint, with 7-OEL meeting the CLP classification "Skin Sensitiser Cat. 1".

 

Respiratory sensitization

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

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation, other

Remarks:

QSAR analysis

Type of information:

(Q)SAR

Adequacy of study:

key study

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 of oct-7-enal 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
- Chemical elements (subcategorization)
- Organic functional groups, Norbert Haider

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 35 values.


5. APPLICABILITY DOMAIN
The target chemical, oct-7-enal 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 DNA binding by OASIS v.1.4

b) Referential boundary:
The target chemical should be classified as Aldehyde AND Carbonyl compound by Organic functional groups, Norbert Haider (checkmol)

c) Referential boundary:
The target chemical should be classified as 1,2-aminoalcohol OR 1,2-diol OR Acetal OR Alcohol OR Alkene OR Alkyl bromide OR Alkyl chloride OR Alkyl fluoride OR Alkyl halide OR Alkyl iodide OR Alkylarylether OR Alkyne OR Alpha-aminoacid OR Alpha-hydroxyacid OR Aminal OR Amine OR Anion OR Aromatic compound OR Aryl bromide OR Aryl chloride OR Aryl halide OR Aryl iodide OR Azo compound OR Carbamic acid derivative OR Carbamic acid ester (uretane) OR Carbonic acid derivative OR Carbonic acid diester OR Carboxylic acid OR Carboxylic acid amide OR Carboxylic acid anhydride OR Carboxylic acid derivative OR Carboxylic acid ester OR Carboxylic acid imide OR Carboxylic acid prim. amide OR Carboxylic acid salt OR Carboxylic acid sec. amide OR Carboxylic acid subst. imide OR Carboxylic acid tert. amide OR Cation OR CO2 derivative (general) OR Dialkylether OR Diarylether OR Enol OR Enolether OR Ether OR Halogen derivative OR Hemiacetal OR Heterocyclic compound OR Hydroxy compound OR Isocyanate OR Isothiocyanate OR Ketone OR Lactam OR Lactone OR Nitrile OR Nitro compound OR No functional group found OR N-oxide OR Organometallic compound OR Oxime OR Phenol OR Phosphine OR Phosphoric acid derivative OR Phosphoric acid ester OR Primary alcohol OR Primary aliphatic amine OR Primary amine OR Primary aromatic amine OR Quaternary ammonium salt OR Secondary alcohol OR Secondary aliphatic amine OR Secondary amine OR Secondary aromatic amine OR Secondary mixed amine (aryl, alkyl) OR Sufoxide OR Sulfenic acid derivative OR Sulfone OR Sulfonic acid OR Sulfonic acid derivative OR Sulfuric acid OR Sulfuric acid derivative OR Sulfuric acid monoester OR Tertiary alcohol OR Tertiary aliphatic amine OR Tertiary amine OR Tertiary mixed amine OR Thiocarbonic acid derivative OR Thiocarboxylic acid derivative OR Thiocarboxylic acid ester OR Thioether OR Urea by Organic functional groups, Norbert Haider (checkmol)

d) Referential boundary:
The target chemical should be classified as Aldehyde AND Allyl by Organic Functional groups (nested)

e) Referential boundary:
The target chemical should be classified as Alkane branched with quaternary carbon OR Alkane, branched with tertiary carbon OR Cycloalkene OR Isopropyl OR Overlapping groups OR Terpenes by Organic Functional groups (nested)

f) Parametric boundary:
The target chemical should have a value of log Kow which is >= 0.346

g) Parametric boundary:
The target chemical should have a value of log Kow which is <= 4.67

6. ADEQUACY OF THE RESULT
The predicition is based on 35 neighbours' values, 29 of them equal to prediction. Prediction confidence is measured by the p value = 0.0000584

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 0312799-TOX3 attached

Parameter:

other: n/a

Variability:

n/a

Remarks on result:

not measured/tested

Interpretation of results:

Category 1 (skin sensitising) based on GHS criteria

Conclusions:

In conclusion, the in silico estimates from the OECD Toolbox indicates that 7-OEL is predicted to be a skin sensitizer based on protein binding, deemed to be an applicable domain. As protein binding provides the highest predictive power in correctly identifying potential skin sensitisers, no further work is considered necessary in addressing this endpoint, with 7-OEL meeting the CLP classification "Skin Sensitiser Cat. 1".

Executive summary:

In conclusion, the in silico estimates from the OECD Toolbox indicates that 7-OEL is predicted to be a skin sensitizer based on protein binding, deemed to be an applicable domain. As protein binding provides the highest predictive power in correctly identifying potential skinsensitisers, no further work is considered necessary in addressing this endpoint, with 7-OEL meeting the CLP classification "Skin Sensitiser Cat. 1".

Reference 2

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

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
The test article, Octen-1-al meets the classiifcaiton of skin sensitisation from data generated from in silico estimates from the OECD Toolbox indicates that 7-OEL is predicted to be a skin sensitizer based on protein binding, deemed to be an applicable domain. In accordance with the ECHA Chapter R.7a guidance, a waiver is requested and therefore a skin sensitisation study to address this endpoint is not required. As protein binding provides the highest predictive power in correctly identifying potential skin sensitisers, no further work is considered necessary in addressing this endpoint, with 7-OEL meeting the CLP classification "Skin Sensitiser Cat. 1".

Reason / purpose for cross-reference:

data waiving: supporting information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Respiratory sensitisation

Link to relevant study records

Reference

Endpoint:

respiratory sensitisation: in vitro

Data waiving:

study technically not feasible

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Comparison with the CLP criteria

The in silico estimates from the OECD Toolbox indicates that 7-OEL is predicted to be a skin sensitizer based on protein binding, deemed to be an applicable domain. As protein binding provides the highest predictive power in correctly identifying potential skin sensitisers, no further work is considered necessary in addressing this endpoint, with 7-OEL meeting the CLP classification "Skin Sensitiser Cat. 1". The available data are insufficient to allow sub-categorisation to Category 1A or 1B [1].

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

 

References

1.ECHA (European Chemicals Agency). Guidance on the application of the CLP criteria. Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures. Version 4.1, June 2015. Part 3, Section 3.4.2.2.6, pp 345.