(4E)-4-(3,3,4-trimethylcyclopentylidene)butanal

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation / corrosion, other

Remarks:

in silico prediction

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

February 05th, 2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Justification for type of information:

1. SOFTWARE
iSafeRat

2. MODEL (incl. version number)
iSafeRat Skin irritation/corrosion prediction model v1.0: iSafeRat SIC

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
CC1CC(=CCCC=O)CC1(C)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
For details see attached QPRF

- Defined endpoint: Acute skin irritation/corrosion
- Unambiguous algorithm: yes
- Defined domain of applicability: yes
- Appropriate measures of goodness-of-fit: yes
- Mechanistic interpretation: yes

5. APPLICABILITY DOMAIN
- Descriptor domain: inside
- Structural domain: inside
- Mechanistic domain: inside
- Similarity with analogues in the training set: yes

6. ADEQUACY OF THE RESULT
iSafeRat skin irritation/corrosion model was trained with chemicals that had studies for skin irritation/corrosion which allowed to conclude on the GHS/CLP classification criteria. Therefore, the predictions from the iSafeRat SIC are considered to be equivalent to the GHS/CLP classification, as would be expected from an OECD TG 404 experimental study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not applicable

Principles of method if other than guideline:

Model description: The iSafeRat skin irritation/corrosion prediction model determines whether the applied dose of a chemical substance causes cytotoxicity, thereby responsible for erythema and/or oedema as both lesions are driving the classification according to CLP and GHS. The dose applied and the physico-chemical properties of the test substance are the input of a series of algorithms to determine: the substance concentration in the viable epidermis and to establish if this concentration reaches a cytotoxic concentration for the keratinocytes. These concentrations are plotted against the logarithm of the subcooled water solubility of the substances (Log SCLS). The plot is subdivided into corrosive, irritant and non-irritant zones. The test item will fall into one of these zones, thereby allowing a classification.

The iSafeRat skin irritation/corrosion "aldehyde model" has an accuracy of 75% and a sensitivity for irritants (category 2) chemicals of 100% (9 irritant chemicals/9 total), based on the local model’s training set.

GLP compliance:

no

Remarks:

Not applicable (QSAR model)

Test material

Test material information

Constituent 1

Reference substance name:

(4E)-4-(3,3,4R-trimethylcyclopentylidene)butanal

Molecular formula:

C12 H20 O

IUPAC Name:

(4E)-4-(3,3,4R-trimethylcyclopentylidene)butanal

Constituent 2

Reference substance name:

(4E)-4-(3,3,4S-trimethylcyclopentylidene)butanal

Molecular formula:

C12 H20 O

IUPAC Name:

(4E)-4-(3,3,4S-trimethylcyclopentylidene)butanal

Test material form:

liquid

Details on test material:

- SMILES: CC1CC(=CCCC=O)CC1(C)C
- Molecular formula: C12H20O
- Molecular weight: 180.29 g/mol

Test animals

Species:

rabbit

Results and discussion

In vivo

Results

Irritation parameter:

erythema score

Time point:

24/48/72 h

Score:

> 2.3

Reversibility:

other: not applicable (QSAR prediction)

Remarks on result:

positive indication of irritation

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

QSAR prediction

Conclusions:

The test item was predicted as irritant to skin according to Regulation (EC) No. 1272/2008 (CLP) and to GHS using the iSafeRat skin irritation/corrosion v1.0. The test item falls within the applicability domain of the model’s training set and was hence reliably predicted for its skin irritation/corrosion potential. Therefore, this endpoint prediction can be considered reliable with restrictions. The prediction is accorded a Klimisch score K2, based on the results being “derived from a (Q)SAR model, with limited documentation/justification, but validity of model and reliability of prediction considered adequate.”

Executive summary:

The test item was predicted as irritating to skin using the iSafeRat skin irritation/corrosion prediction model. The prediction is considered reliable based on the evaluation of the applicability domain of the model, relative to the test item and the quality of the data used to generate the prediction.