3-(isodecyloxy)propylamine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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, Statistica 7

2. MODEL (incl. version number) : Nonlinear QSAR model for acute oral toxicity of rat, model 3.3.8

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : 3D Mol file used for prediction

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QMRF attached separately
- Defined endpoint: 4.Human health effects 4.2.Acute oral toxicity
The acute oral toxicity is determined using the OECD 423 (EU B.1 tris) test guideline. Acute oral toxicity testing allows to obtain the information on the biologic/toxic activity of a chemical. Currently, the basis for toxicologic classification of chemicals is the median lethal dose LD50, mg/kg b.w.), which is defined as the statistically derived dose required to kill half the members of a tested population. Animals are observed individually after dosing at least once during the first 30 minutes, periodically during the first 24 hours, with special attention given during the first 4 hours, and daily thereafter, for a total of 14 days.
- Unambiguous algorithm: Nonlinear QSAR: Backpropagation Neural Network (Multilayer Perceptron) regression. The algorithm is based on regression neural network predictor with structure 9-5-1.
- Defined domain of applicability: 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 ±30%. Applicability domain based on training set: a)diverse set organic compounds (phenols, carboxylic acids, carbonyl-, nitro-, amino-, halogeno-, P-conataining derivatives, etc); b)The model is suitable for compounds that have descriptors values in the followin range;
Desc 1 2 3 4 5 6 7 8 9
min 10.59 0.00 2.37 0.00 0.00 -345.84 155.19 0.00 -188.86
max 582.27 0.03 27.62 22.55 124.42 461.31 17030.22 0.49 0.00
- Appropriate measures of goodness-of-fit and robustness and predictivity:
a) Statistics for goodness-of-fit: Training LogLD50 Selection LogLD50 Test LogLD50
Data Mean 0.64 0.42 0.49
Data S.D. 0.95 1.00 0.91
Error Mean 0.00 0.05 0.17
Error S.D. 0.73 0.74 0.76
Abs E. Mean 0.53 0.57 0.55
S.D. Ratio 0.77 0.74 0.83
Correlation 0.76 0.76 0.75
b) Robustness - Statistics obtained by other methods: RMS (Training)= 0.149,, RMS(Selection)= 0.151, RMS(Test) = 0.158, In this ANN were used 2 sets randomly chosen (40) to train and test the network – selection set and test set, see also Statistics for goodness-of-fit:
c) Predictivity - Statistics obtained by external validation: see Statistics for goodness-of-fit: and Robustness - Statistics obtained by other methods
Predictivity - Assessment of the external validation set: The descriptors for the test set are in the limit of applicability, see Statistics for goodness-of-fit: and Robustness - Statistics obtained by other methods
- Mechanistic interpretation: Since the ANN is a more complex predictor than a linear model, it is difficult to analyze the direct relation between the property and the descriptors. However, general trends and analysis can be drawn based on the most significant descriptors in the net. According to these and the generally accpeted scientific understanding , the acute oral toxicity is strongly dependent on the stability and reactivity of chemicals, in particular the presence of heteroatoms like oxygen, nitrogen, phosphorus, and halogenides. One of the most important descriptor for this set was charged surface area of the N atoms. There is slight indication that the more charged is the N the more toxic is the compound. The same holds for charged surfacte area for Cl atoms. The hydrogen acceptor/donor ability of O and their reactivity indeces are encoded in HA dependent HDCA-2/SQRT(TMSA) (AM1) and Avg electrophilic reactivity index (AM1) for O atoms descriptors indicating oposite relation with LogLD50. These parameters are likely to be related to solubility and LogP of the compounds making them less toxic. Structural parameters as Bonding Information content (order 0), Gravitation index (all atom pairs) (AM1) define that the compound complexation and its bulk characteristics are aslo important for LD, especially for molecular phenomena in liquid media.

5. APPLICABILITY DOMAIN
- Descriptor domain: All descriptor values for 3-(isodecyloxy)propylamine fall in the applicability domain (training set value ±30%).
- Structural domain: 3-(isodecyloxy)propylamine is structurally similar to the training set compounds, the training set contains compounds carbonyl and amide groups, linear and branched alkyl chains. The training set contains compounds of similar size to the studied molecule.
- Mechanistic domain: 3-(isodecyloxy)propylamine 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 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 rather well estimated within the model.
- Metabolic domain: 3-(isodecyloxy)propylamine is considered to be in the same metabolic domain as the molecules in the training set of the model due to the structural similarity.

6. ADEQUACY OF THE RESULT
- Regulatory 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")
- 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.
- Outcome: See section 3.2(e) of QPRF protocol for the classification of the prediction in light of the regulatory purpose described above.
- Conclusion: Considering the above, the predicted result can be considered adequate for the regulatory conclusion described in "Regulatory purpose"

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(isodecyloxy)propylamine

EC Number:

250-056-7

EC Name:

3-(isodecyloxy)propylamine

Cas Number:

30113-45-2

Molecular formula:

C13H29NO

IUPAC Name:

3-[(8-methylnonyl)oxy]propan-1-amine

Test material form:

liquid

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Details on study design:

Acute oral LD50 data were taken from the Registry of Toxic Effects of Chemical Substances (RTECS) database. RTECS is a compendium of data extracted from the open scientific literature. The data are recorded in the format developed by the RTECS staff and arranged in alphabetical order by prime chemical name. Specific numeric toxicity values such as LD50, LC50, TDLo, and TCLo are noted as well as species studied and route of administration used. For each citation, the bibliographic source is listed thereby enabling the user to access the actual studies cited. The RTECS is a toxicology database of over 168,000 chemicals compiled, maintained, and updated by the U.S. National Institute of Occupational Safety and Health (NIOSH). The LD50 values of tested substances were translated to logarithmic scale (logLD50) to reduce the range of the data.

Results and discussion

Effect levels

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 145 mg/kg bw

Remarks on result:

not measured/tested

Any other information on results incl. tables

Exposure rout	Category 1	Category 2	Category 3	Category 4
LD50 (oral tox.) (mg/kg)	ATE < 5	5 < ATE < 10	50 < ATE < 300	300 < ATE < 2000

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The LD50 of test item, 3-(isodecyloxy)propylamine, is 145 mg/kg.

Executive summary:

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):

xposure rout	Category 1	Category 2	Category 3	Category 4
LD50 (oral tox.) (mg/kg)	ATE < 5	5 < ATE < 10	50 < ATE < 300	300 < ATE < 2000

On the given scale, 3-(isodecyloxy)propylamine has Category 2, therefore “Category 3” is assigned.