3-(isodecyloxy)propylamine

Short-term toxicity to aquatic invertebrates

Administrative data

Endpoint:

short-term toxicity to aquatic invertebrates

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

2. MODEL (incl. version number) : QSAR model for Acute toxicity to Daphnia magna (LC50), Model 4.0.4. Molcode Ltd.

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
JRC Q19-10-30-299, enclosed separately
- Defined endpoint: Ecotoxic effects 3.1.Short-term toxicity to Daphnia (immobilisation)
Acute toxicity 48h LC50 (50% of lethal concentration). This is the concentration which immobilizes 50% of the Daphnia in a test batch within 48 h.
- Unambiguous algorithm: 2D and 3D regression-based QSAR
multilinear regression QSAR, multilinear regression QSAR derived with BMLR (Best Multiple Linear Regression) method
log(LC50) = -4.904
-2.272*Average Bonding Information content (order 2)
+0.377*HOMO - LUMO energy gap (AM1)
+4.653E-003*HPSA Polar (AM1) part of SASA
-1.240E-002*Molecular weight
+0.256*min(#HA, #HD) (AM1)
- Defined domain of applicability:
Applicability domain based on training set: a) by chemical identity: Organic Compounds (hydrocarbons, aliphatic alcohols, phenols, ethers, and esters; anilines, amines, nitriles, nitroaromatics, amides, and car bamates; urea and thiourea derivatives; isothiocyanates; thioles; phosphorothionate and phosphate esters; and halogenated derivatives). b) by descriptor value range: The model is suitable for compounds t hat have the descriptors in the following minimal-maximal range:
Average Bonding Information content (order 2): 0.279 - 0.976
HOMO - LUMO energy gap (AM1): 4.97 - 14.7
HPSA Polar (AM1) part of SASA: 0 - 392
Molecular weight: 44.1 - 505
min(#HA, #HD) (AM1): 0 - 5
Chemicals in the same structural domain as training set (similar functionality) Range of descriptor values in training set with ±30% confidence. Descriptor values must fall between maximal and minimal descriptor values o f training set ±30%.
- Appropriate measures of goodness-of-fit and robustness and predictivity:
a) Statistic for goodness-of-fit: R2 = 0.741 (Correlation coefficient); s2 = 0.903 (Standard error of the estimate); F = 108 (Fisher function)
b) Robustness: Statistic obtained by leave-one-out cross-validation: R2CV = 0.725
Statistic obtained by leave-many-out cross-validation: R2CVMO = 0.719
Statistics obtained by other methods: ABC analysis (2:1 training : prediction) on sorted (in increased order of endpoint value) data divided into 3 subsets (A;B;C). Training set formed with 2/3 of the compounds (set A+B, A+C, B+C) and validation set consisted of 1/3 of the compounds (C, B, A). average R2 (fitting) = 0.747, average R2 (prediction) = 0.712
- Mechanistic interpretation: The toxicity baseline (as it is usually modeled by logP) is defined here with combination of "Molecular weight", "Average Bonding Information content (order 2)", "HPSA Polar (AM1) part of SAS A" and "min(#HA, #HD) (AM1)". "Molecular weight" defines generally the mass and size of the structure; "Average Bonding Information content (order 2)" accounts the bonding complexity, i.e. aromatic, single, double, tr iple bonds, where also taking into account a heteroatoms; "HPSA Polar (AM1) part of SASA" shows the amount of polar surface area; and "min(#HA, #HD) (AM1)" counts the hydrogen bonding. All these descriptors aff ect more or less hydrophobicity - the baseline. Indirectly they are also related with other mode of action (like polar narcosis). For instance, heteroatoms, polar surface area and hydrogen bonding are important factors fo r different MOA. Specifically "HOMO - LUMO energy gap (AM1)" is defining the electronic hardness of molecules and is an important descriptor to define the deviation from baseline.

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 functio nalities. The structural analogues are relatively similar to the studied compound, covering all the chemical features. 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.
- 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.
- Other considerations (as appropriate):

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 (regulat ory) scale values have been presented.
- Outcome: See section 3.2(e) 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 202 (Daphnia sp. Acute Immobilisation Test)

Principles of method if other than guideline:

Acute toxicity for Daphnia is expressed as the median effective concentration EC50. The concentrations of the substances are given in mol per litre (mol/L). Those animals which are not able to swim within 15 seconds after gentle agitation of the test batch are considered to be immobile.
Some studies use mortality (LC50) and immobilization (EC50) as identical endpoints in the context of daphnid toxicity, as is, for example, reported in the toxicity analysis of parathion that is also included in the presently selected AQUIRE data set [2].
From the U.S. EPA database AQUIRE, acute toxicity values (48 h LC50) for the Daphnia magna were collected for a total of 380 compounds.
When multiple test values were found for one substance, these values were checked for consistency. If values differed by more than a factor of 30 from the closest one in a group of at least three other references, the aberrant value was discarded so as to remove outliers from the data set. Of all the remaining values for a given substance, the arithmetic mean was taken as the valid experimental value.
From the initial set of 1067 LC50 data, 77 values were excluded as outliers as described above, which led to a set of 349 chemicals with at least one LC50 value per substance.
Subsequently, 49 chemicals were excluded because their LC50 values exceeded the predicted water solubility or because they contained metal atoms or were inorganic, leading to the final set of 300 organic compounds that cover a log Kow (octanol/water partition coefficient) range from -2 to 8.

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

Sampling and analysis

Analytical monitoring:

no

Test solutions

Vehicle:

no

Test organisms

Test organisms (species):

Daphnia magna

Results and discussion

Effect concentrations

Key result

Duration:

48 h

Dose descriptor:

LC50

Effect conc.:

> 100 mg/L

Nominal / measured:

estimated

Conc. based on:

not specified

Basis for effect:

mobility

Reported statistics and error estimates:

Experimental data from different labs has been used. On previously explained reason (see 3.6), the averge experimental error, which accounts as well an error caused by inerlaboratory differences, might be reasonably large. Since the autors do not provide the results from interlaboratory calibrations, it is difficult or evenimpossible to estimate exact error.
Statistics:
max value: -0.460
min value: -10.1
standard deviation: 1.75
skewness: -0.259

Any other information on results incl. tables

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
LC50 (mg/l)	LC50 ≤ 1.0	1.0 < LC50 ≤ 10	10 < LC50 ≤ 100	LC50 > 100.0

On the above scale, the studied compound falls to the “No Category” classification. This allows considering the toxicity as practically non-toxic.

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

The test item, 3-(isodecyloxy)propylamine, is praciticaly non-toxic, based on the results.

Executive summary:

The estimated concentratoin is  LC₅₀> 100.0. Based on this results, the test item, 3-(isodecyloxy)propylamine, is praciticaly non-toxic.