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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
(Q)SAR
Adequacy of study:
key study
Study period:
15/10/2020
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Justification for type of information:
1. SOFTWARE: QSAR Turu 2, Tartu, 51014, Estonia http://www.molcode.com

2. MODEL (incl. version number) : QSAR model for Eye irritation (Draize test), Model 3.3.8

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL :
SMILES: CCCCCCON=O, not used for prediction
Other structural representation: 3D Mol file used for prediction

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF or providing a link]
- Defined endpoint: 4.Human health effects 4.9.Eye irritation/corrosion
- Unambiguous algorithm: QSAR model for Eye irritation (Draize test), Reference to QMRF: Q2-22-1-135 (http://qsardb.jrc.ec.europa.eu/qmrf/), attached separately
- Defined domain of applicability:
a) Descriptor domain
b) Stuctural domain
c) Mechanism domain
d) Metabolic domain: Hexyl nitrite is considered to be in the same metabolic domain as the molecules in the training set of the model due to the structural similarity.
- Appropriate measures of goodness-of-fit and robustness and predictivity: The training set is not from one lab but a collection. However, it has been shown to be of reasonable quality, the significant statistical quality of the model support reliable predictions. Experimental data based on Draize tests are always difficult to model and interpret due the somewhat arbitrary evaluation of results as well as the individual response of test animals. The studied compound is relatively similar to the training set compounds, adding to certainty. The structural analogues were all evaluated correctly within the present model, strongly supporting consistency. Considering the dataset, model statistical quality and prediction reliability, a reliability score (Klimisch score) “2” could be assigned to the present prediction.The prediction reliability is estimated as 86 %
- Mechanistic interpretation: Overall, the eye irritation is known to have positive correlation with the polarity/water solubility of a compound. The key issues for an irritant are the transport from eye surface into the biophase, binding to the phospholipid membrane and possible binding to the receptor. In this range of compounds, the length of the alkyl chains together with the branching has a strong influence on the toxicity of the compound. The presence or absence of hydrogen bonding groups also has a significant effect.

5. APPLICABILITY DOMAIN
- Descriptor domain: All descriptor values for Hexyl nitrite fall in the applicability domain (training set value ±30%).
- Structural domain: Hexyl nitrite is structurally relatively similar to the model compounds. The training set contains compounds of similar size to the studied molecule.
- Mechanistic domain: Hexyl nitrite is structurally relatively similar to the model compounds. The training set contains compounds of similar size to the studied molecule.
- Similarity with analogues in the training set: Overall, the structural analogues from the model are relatively similar to the studied compound. The main structural feature is the ester functionality, apart from the saturated alkyl chains. The descriptor values of the analogues are close to those of the studied compound. The analogues are considered to be within the same mechanistic domain. All the analogues are very well estimated within the model. The following aspects have been considered for the selection and analysis of structural analogues:
Presence and number of common functional groups;
Presence and relevance of non-common functional groups;
Similarity of the ‘core structure’ apart from the (non-)common functional groups;
Potential differences due to reactivity;
Potential differences due to steric hindrance;
Presence of structural alerts;
Position of the double bonds;
Presence of stereoisomers.

6. ADEQUACY OF THE RESULT
6.1Regulatory purpose:
The present prediction may be used for preparing the REACH Joint Registration Dossier on the Substance(s) for submission to the European Chemicals Agency (“ECHA”) as required by Regulation (EC) N° 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals ("REAC H") and as required by Biocide Product Directive 98/8/EC ("98/8/EC").
6.2 Approach for regulatory interpretation of the model result
The predicted result has been presented in the formats directly usable for the intended regulatory purposes, both the numeric value and the transferred (regulatory) scale values have been presented.
6.3 Outcome
See section 3.2(e) for the classification of the prediction in light of the regulatory purpose described in 6.1.
6.4 Conclusion
Considering the above, the predicted result can be considered adequate for the regulatory conclusion described in 6.1.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2020
Report date:
2020

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals / tissue source

Species:
rabbit
Strain:
not specified

Test system

Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (or weight equivalent)

Duration of treatment / exposure:
21 days of application

Results and discussion

In vivo

Results
Irritation parameter:
other: MMAS
Time point:
21 d
Score:
ca. -3.08
Max. score:
2.37
Reversibility:
not reversible

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
The predicted value corresponds to “strong irritant” on the scale of “non irritant, weak irritant, moderate irritant, strong irritant, very strong irritant” in the framework of the model. The predicted value would correspond to the “Category 1” classification.
Executive summary:

The predicted value corresponds to “strong irritant” on the scale of “non irritant, weak irritant, moderate irritant, strong irritant, very strong irritant” in the framework of the model.

Following the EU acute toxicity hazard categories and acute toxicity estimates (ATE) defining the respective categories according to Regulation (EC) No 1272/2008 on the classification, labelling and packaging of substances and mixtures (CLP Regulation) defined as:

 Category 1  Category 2  No Category
 Irreversible eye effects - seriously damaging to eyes  reversible eye effects - irritation to eyes

 no eye effects

The predicted value would correspond to the “Category 1” classification.