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EC number: 915-730-3
CAS number: -
Test material is within the applicability domain of the model (see details on test material):
- Model is about organic liquids
- Training set has MW range of 30-268.5 g/mol
- Training set of the model contains 5/119 substances with ketons
- Model hypothesis: smaller molecules are more likely to penetrate into eye and cause irritation than larger chemicals
- Model does not discuss the metabolic domain (parent compound is expected to cause the effect)
Considerations on structural analogues (2,6-dimethyl-4-heptanone and 6,10,14-trimethyl-2-pentadecanone):
The presented analogues are aliphatic organics containing C, H, O atoms, and the difference with the predicted chemical OTNE is that the chemical cyclic features and has one unsaturated bond. This dissimilarity is not expected to cause other properties, because the longer aliphatic chain is expected to bend and may have similar cyclic features as OTNE. The bioavailability of the chemicals is expected to be the highest for the smaller molecule with the lowest log Kow. The bioavailability of OTNE and the other analogue are suspected to be similar. The cyclic structure may be somewhat less bioavailable than the aliphatic chains. At the other hand the log Kow of the aliphatic chain is somewhat higher. The keton group of OTNE is expected to be somewhat less electrophilic than the two analogues presented due to some hindrance of a methyl group.
The uncertainty of the prediction:
The uncertainty of the prediction is within the uncertainty of the model: 98% correct predictions for negatives. It is unlikely that this prediction is a false negative because of additional applicability domain reasoning considering physical state, bioavailability, structural alert and reactivity considerations are strengthening the prediction besides OTNE being within the applicability domain of the model. Also the false negative chemical, polyethylene glycol butyl ether, is not similar to OTNE.
The chemical and biological mechanisms according to the model underpinning the predicted result:
The model is based on the hypothesis that smaller chemicals are more likely to penetrate into the eye and cause irritation than larger chemicals. Consistent with this hypothesis was the finding of Rosenkranz that the mean MW of irritants is significant lower than the mean MW of non-irritants (Worth and Cronin, 2003).
The substance has a MW of 234 g/mol, which is higher than the models' threshold value (137 g/mol) for prediction of eye irritation indicating that the substance is not an eye irritant. Additionally, two structural analogues (2,6-dimethyl-4-heptanone, 6,10,14-trimethyl-2-pentadecanone) of OTNE are classified as not irritating to the eyes.
The model of AP Worth and MTD Cronin as published in Journal of
Molecular Structure (TheoChem) 622 (2003) 97-111 ("The use of
discriminant analysis, logistic regression and classification tree
analysis in the development of classification models for human health
effects") was used to predict the irritating potential of OTNE based on
its molecular weight and structural analogues.
The substance has a MW of 234 g/mol, which is higher than the model's
threshold value (137 g/mol) for prediction of eye irritation.
Additionally, two structural analogues (2,6-dimethyl-4-heptanone,
6,10,14-trimethyl-2-pentadecanone) of OTNE are classified as not
irritating to the eyes.
Based on the predicted values in the model, the substance OTNE does not
need to be classified as irritant (molecular weight higher than
threshold value and non-irritating property of structural analogues)
Tabulated summary on the QSAR prediction, the (Q)SAR methodology and the
relevance for REACH:
Reliability of prediction
Scientific validity of
Relevance for REACH C&L
QSAR based on OECD TG 405 information and DSD criteria
REACH requires information similar to OECD TG 405
Prediction according to algorithm: OTNE has MW of 234, which is much > 137 and therefore not an eye irritant
Liquid organic substances with MW >137 are not eye irritants
(Q)SARs are allowed methodology when used according to Annex XI
OTNE is within the domain, considering i) being a liquid; ii) MW range used in the model and; iii) other cyclic ketons are present in the training set
See substances in training set, cyclic ketons are included
Eye irritation hazards for OTNE has to be assessed under REACH
Limited, because OTNE does not have additional groups which may lead to higher eye irritation e.g. higher electrophilicity
Limited, see paper of Worth and Cronin, 2000
The uncertainty of the result is limited, because OTNE is within the domain
Mode of action explanation
OTNE has insufficient reactive properties to cause eye irritation or corrosion
Not explained, but liquids with MW > 137 are expected to limitedly penetrate the eye barriers
The QSAR result of OTNE covers the mode of actions in OECD TG 405 because the training set is based on this type of tests
Not an eye irritant according to DSD
Uses DSD criteria
Result is based on DSD criteria
Actual use into
Not an eye irritant
Sufficiently adequate, no further information needed
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