3-(isodecyloxy)propylamine

Toxicity to aquatic algae and cyanobacteria

Administrative data

Endpoint:

toxicity to aquatic algae and cyanobacteria

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, Nonlinear ANN QSAR model for Toxicity to algae

2. MODEL (incl. version number) : QSAR model for Toxicity to algae of diverse organics, Model 4.0.4

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 Added separately
- Defined endpoint: Ecotoxic effects 3. 2.Short-term toxicity to algae (inhibition of the exponential growth rate); C.3 in REACH classification. The EC50 is the concentration (mM) that induces toxicity response halfway between the baseline and maximum after 96 h.
- Unambiguous algorithm: Nonlinear QSAR: Backpropagation Neural Network (Multilayer Perceptron) regression. The algorithm is based on neural network predictor with structure 4-4-1 Standard Backpropagation Neural Network (Multilayer Perceptron) regression using Levenberg-Marquardt optimization algorithm
- Defined domain of applicability: Quantitative approach - range of descriptor values in training set with augmented with ±30% confidence Descriptor values must fall between maximal and minimal descriptor values (see5.1) of training set augmented by ±30%. By descriptor value range (between min and max values): The model is suitable for compounds (small organic molecules with functional groups as halogens, nitro, hetero benzens, alcohols) that have descriptors in the following range augmented with the confidence in 5.2: (the following is in table format - first row Descs IDs, second row- min desc values, third row - max desc values)
Desc 1 2 3 4
min 0.00 45.08 0.62 5.08
max 1.34 379.66 1.04 13.37
- Appropriate measures of goodness-of-fit and robustness and predictivity:
a) Statistic for goodness-of-fit: (the following information is in Table format 7 rows and 4 columns)
Training pEC50 Selection pEC50 Test pEC50
Data Mean 1.94 1.56 2.10
Data S.D. 1.24 1.09 1.16
Error S.D. 0.63 0.59 0.68
Abs E. Mean 0.45 0.51 0.60
S.D. Ratio 0.51 0.54 0.59
Correlation 0.86 0.84 0.81
b) Robustness - Statistic obtained by other methods: RMS (Training)= 0.11; RMS(Selection)= 0.10; RMS(Test) = 0.12
c) Predictivity - Statistic obtained by external validation: See 6.7 and 6.12 of QMRF report
- Mechanistic interpretation: The descriptors in the ANN were selected by the method described in section 4.4 which selects features with highest correlation coefficient in respect to the property. Further the combinatorial construction of various ANN topologies led to selection of 4 descriptors. This is a perfect example where the "linearity" of the descriptors can be further extended to nonlinear relation with the property based on the ANN. The descriptor Square root of Charged (Zefirov) Surface Area of C atoms has positive correlation with pEC50 indicating that the increase of the descriptor would lead to decrease of EC50. The C atom is "more" charged where its neighbours are hetero atoms as O, N (also halogens). It is likely that this descriptor contribute to membrane permeability and polar narcosis. Similar analogy can be done for the HOMO - LUMO energy gap (AM1) descriptor, which is related the reactivity of the atoms. However, in this case this descriptor has negative correlation with the property. The most reactive centers in the molecule would probably react with the medium or the membrane and would change (decay) the compound making it less toxic to Algae. The remaining two descriptors Globularity index (AM1) and Molecular weight are related to the bulk properties of the compounds. These two descriptors can be addressed to features governing the nonspecific interactions describing nonpolar narcosis.

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 relatively similar to the model compounds; 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 experimental acute toxicity values for compounds of similar functionalities are somewhat scattered in the toxicity scales depending on the molecular size and other functionalities. 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 very well estimated within the model.
The following aspects have been considered for the selection and analysis
- 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 above.

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 201 (Alga, Growth Inhibition Test)

Principles of method if other than guideline:

The test alga was an unicellular green algal species Selenastrum capricornutum Printz (also known as Pseudokirschneriella subcapitata and Raphidocelis subcapitata) and the culture medium 10% Z 8. The inoculum was taken from a stock culture in the exponential growth phase.
The initial algal density was 104 ± 10% cells/mL. The test algae were cultivated in 100-mL solutions in 250-mL sterile, foam-plugged Erlenmeyer flasks with three replicates of each concentration. In addition, there were two control cultures: Selenastrum cells in culture medium and in acetone series. There were also controls for chemicals without algae. The cultures were incubated at +22 ± 20 C in continuous illumination of approximately 72 μE m-2 s-1 (Airam L 40 W 35). The growth of cultures was followed by measuring the cell density after 24, 48, 72 and 96 hr by means of an electronic particle counter (Coulter Counter Z B). The effect of acetone on the growth of the cultures was eliminated by comparing the growth of test cultures with the growth of acetonecontrols. The results, as percent of control, were calculated as a mean value of the cell density of the triplicates after one test series. In Selenastrum assays, the EC50-values were estimated from semilogarithmic paper using cell density after 96 hr and areal comparison of growth curves during 0-96 hr incubation (ISO 1983).

GLP compliance:

not specified

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 organisms

Test organisms (species):

Raphidocelis subcapitata (previous names: Pseudokirchneriella subcapitata, Selenastrum capricornutum)

Details on test organisms:

The test algae were cultivated in 100-mL solutions in 250-mL sterile, foam-plugged Erlenmeyer flasks with three replicates of each concentration. The cultures were incubated at +22 ± 20 C in continuous illumination of approximately 72 μE m-2 s-1 (Airam L 40 W 35). The growth of cultures was followed by measuring the cell density after 24, 48, 72 and 96 hr by means of an electronic particle counter (Coulter Counter Z B)..

Study design

Test type:

not specified

Water media type:

not specified

Limit test:

no

Total exposure duration:

96 h

Test conditions

Reference substance (positive control):

yes

Remarks:

Acetone: In addition, there were two control cultures: Selenastrum cells in culture medium and in acetone series. There were also controls for chemicals without algae.

Results and discussion

Effect concentrations

Key result

Duration:

96 h

Dose descriptor:

EC50

Effect conc.:

ca. 7.27 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

growth rate

Details on results:

The effect of acetone on the growth of the cultures was eliminated by comparing the growth of test cultures with the growth of acetonecontrols. The results, as percent of control, were calculated as a mean value of the cell density of the triplicates after one test series. In Selenastrum assays, the EC50-values were estimated from semilogarithmic paper using cell density after 96 hr and areal comparison of growth curves during 0-96 hr incubation (ISO 1983).

Any other information on results incl. tables

Category	Acute 1	Acute 2	Acute 3	No Category
EC50 (mg/l)	EC50 ≤ 1.0	1.0 < EC50 ≤ 10	10 < EC50 ≤ 100	EC50 > 100.0

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

Following the “hazardous to the aquatic environment” categories defining the respective categories according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). The predicted value for the studied compound falls under the “Acute 2” classification.

Executive summary:

Following the “hazardous to the aquatic environment” categories defining the respective categories according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS).

Category	Acute 1	Acute 2	Acute 3	No Category
EC50(mg/l)	EC50≤ 1.0	1.0 < EC50≤ 10	10 < EC50≤ 100	EC50> 100.0

The predicted value for the studied compound falls under the “Acute 2” classification.