3-(isodecyloxy)propylammonium acetate

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

10/12/2021 - 17/12/2021

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 : QSARModel 3.3.8; Statistica 7, StatSoft Ltd. Turu 2, Tartu, 51014, Estonia, http://www.molcode.com

2. MODEL (incl. version number): QSARModel 3.3.8; Statistica 7 (Nonlinear QSAR: Backpropagation Neural Network (Multilayer Perceptron) regression)

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : 3D Mol file used for prediction
SMILES: CC(C)CCCCCCCOCCC[NH3+].CC(=O)[O-], not used for prediction
InCHI: InChI=1S/C13H29NO.C2H4O2/c1-13(2)9-6-4-3-5-7-11-15-12-8-10-14;1-2(3)4/h13H,3-12,14H2,1-2H3;1H3,(H,3,4), not 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 and/or QPRF or providing a link]
- Defined endpoint: Human health effects 4.16. In vivo pre-natal-developmental toxicity (Dependent variable: Presence or absence of toxicity (indicated as Toxicity Index +1 and -1))
- Unambiguous algorithm: The algorithm is based on neural network predictor with structure 8-8-1 Standard Backpropagation Neural Network (Multilayer Perceptron) classification
- Defined domain of applicability: Applicability domain based on training set: By descriptor value range (between min and max values): The model is suitable for compounds (including ethers, esters, amides, amines,halides, aromatic, aliphatic functional groups) that have the descriptors in the following range augmented with the confidence in 5.2 (Method used to assess the applicability domain):
Desc ID
See 4.3 1 2 3 4 5 6 7 8
Desc 1 2 3 4 5 6 7 8
Min 6.11 3.24 3.24 224.18 0.00 1.13 46.07 0.00
Max 13.80 28.87 28.83 4313.03 0.42 15.21 627.94 0.31
Method used to assess the applicability domain: presence of functional groups in structures; Range of descriptor values in training set with ±30% confidence; Descriptor values must fall between maximal and minimal descriptor values (see5.1) of training set augmented by ±30%.
- Appropriate measures of goodness-of-fit and robustness and predictivity: Training negatives Training positives Selection negatives Selection positives Test negatives Test positives
Total105.0076.0025.0015.0023.0017.00
Correct100.0068.0020.0012.0016.0012.00
Wrong5.008.005.003.007.005.00
Correct(%)95.2489.4780.0080.0069.5770.59
Wrong(%)4.7610.5320.0020.0030.4329.41
- Mechanistic interpretation: The mechanistic picture of the model is complicated due to the nature of the ANN(artificial neural network). In addition, it cannot be given easy interpretation from mechanistic viewpoint because of the for the classification of the property in two categories. However, it can be concluded that model descriptors are related to structural, electrostatic and hydrogen donor/acceptor ability of the compounds. Moreover, one of the most significant descriptor in

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain: All descriptor values for 3-(isodecyloxy)proplyammonium acetate fall in the applicability domain (training set value ±30%).
- Structural domain: 3-(isodecyloxy)proplyammonium acetate is structurally relatively similar to the model compounds. The training set contains compounds of similar size to the studied molecule.
- Mechanistic domain: 3-(isodecyloxy)proplyammonium acetate is considered to be in the same mechanistic domain as the molecules in the training set as it is structurally similar to the model compounds.
- Similarity with analogues in the training set: The experimental acute inhalation toxicity values for compounds of similar functionalities fall mostly to the “Category 3” - “Category 4” region, with obvious dependence on the particular structural features. The structural analogues are relatively similar to the studied compound. 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 relatively 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
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]
4.1Regulatory 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, Authorization and Restriction of Chemicals ("REACH") and as required by Biocide Product Directive 98/8/EC ("98/8/EC").
4.2 Approach for regulatory interpretation of the model result: The predicted result has been presented, due to the nature of the experimental dataset the model is based on, in the format of binary classification values, which can be used as supportive material for certain regulatory purposes.
4.3 Outcome: See section 3.2(e) for the classification of the prediction in light of the regulatory purpose described in 4.1.
4.4 Conclusion: Considering the above, the predicted result can be considered adequate for the regulatory conclusion described in 4.1.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2021

Report date:

2021

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

- Software tool(s) used including version:
- Model(s) used: QSARModel 3.3.8; Statistica 7, StatSoft Ltd. Turu 2, Tartu, 51014, Estonia, http://www.molcode.com
- Model description: see field 'Attached justification'
- Justification of QSAR prediction: see field 'Attached justification'

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(isodecyloxy)propylammonium acetate

EC Number:

249-166-8

EC Name:

3-(isodecyloxy)propylammonium acetate

Cas Number:

28701-67-9

Molecular formula:

C13H29NO.C2H4O2

IUPAC Name:

3-[(8-methylnonyl)oxy]propan-1-aminium acetate

Test material form:

liquid

Test animals

Species:

rat

Strain:

not specified

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

> 500 - < 750 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: experimental data for different species, including human data

Remarks on result:

not measured/tested

Results (fetuses)

Effect levels (fetuses)

Remarks on result:

not measured/tested

Overall developmental toxicity

Developmental effects observed:

no

Lowest effective dose / conc.:

500 mg/kg bw/day

Treatment related:

not specified

Applicant's summary and conclusion

Conclusions:

Based on the results of perfromed (Q)SAR calculation, the test item 3-(isodecyloxy)propylammonium acetate does not evince the teratogenic properties and is classified as non-toxic (-1).

Executive summary:

The Prenatal developmental toxicity study was performed by the (Q)SAR calculation according to OECD 414. Based on this calculation, the test item 3-(isodecyloxy)propylammonium acetate does not evince the teratogenic properties and is classified as non-toxic (-1).