3-(isodecyloxy)propylamine

Biodegradation in water: screening tests

Administrative data

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

(Q)SAR

Adequacy of study:

key study

Study period:

16/10/2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

1. SOFTWARE : QSAR Model 4.0.4 Molcode Ltd.

2. MODEL (incl. version number) : QSAR for Persistence: Biotic degradation in water (submitted 05.05.2010) - QSAR 2.3.a

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL : 3D Mol file used for prediction, CAS no 30113-45-2, EC no. 250-056-7

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
QMRF attached separately
- Defined endpoint: 2. Environmental fate parameters 3.Persistence: Biodegradation, 2.3.a.Ready/not ready biodegradability
- Unambiguous algorithm: nonlinear regression QSAR, artificial neural networks model with architecture 6-5-1 trained with back propagation of the error
- Defined domain of applicability:
Applicability domain based on training set: a) by chemical identity: diverse set of organic pollutants (aromatic, alphatic and cyclic amines, ketones, alcohols, esters, etc)
b) by descriptor value range: The model is suitable for compounds that have the descriptors in the following minimal-maximal range:
Partial Charged (Zefirov) Surface Area of H atomsLowest resonance energy (AM1) for C - Cl bondsFPSA3 Fractional PPSA (PPSA-3/TMSA)
(Zefirov)Number of halogenide groupsNegatively Charged Surface Area
(Zefirov)Molecular weight
min0.000-13.6490.0000.0009.38344.053
max0.0370.0000.0418.000440.931443.752
- Appropriate measures of goodness-of-fit and robustness and predictivity:
A) Goodness-of-fir: Data Mean2.58
B) Robustness - statistic obtained by other methods: Validation test statistics
C) Predictivity: The source experimental data for the model originate from different labs and different experiment series, adding to uncertainty, however, previous (and present) successful modeling add to the consistence of the data. The significant size of the dataset; the diversity of the structures covering a large parts of the chemical space, and the statistical quality (RMS, correlation coefficients etc.) of the model supports reliable predictions within the margins of the experimental error. The similarity of the analogues together with the correct estimates supports potential prediction consistency.
Considering the dataset size, model statistical quality and prediction reliability, a reliability score (Klimisch score) “2” could be assigned to the present prediction.
The prediction reliability in terms of the persistence category is estimated as 84 %
- Mechanistic interpretation: Because of the nonlinear nature of the ANNs deeper analysis of the descriptor is difficult compared to the normal multilinear analysis. The ANN model descriptors are mainly related to the charge ditributions of the compounds e.g. FPSA3 Fractional PPSA (PPSA-3/TMSA) (Zefirov), Negatively Charged Surface Area (Zefirov), Partial Charged (Zefirov), Surface Area of H atoms. In addition the halogens reactivity plays also important role for the water degradation. Generally the halogens have larger LogT values.
A priori or a posteriori mechanistic interpretation: a posteriori mechanistic interpretation,
Other information about the mechanistic interpretation: Similar interpretation can be found in scientific literature

5. APPLICABILITY DOMAIN
- Descriptor domain: All descriptor values for 3-(isodecyloxy)propylamine fall in the applicability domain (training set value ±30%).
- Structural domains: 3-(isodecyloxy)propylamine is structurally similar to the model compounds, the model contains compounds featuring short alkyl chains and ether functionalities The training set contains compounds of similar size to the studied molecule
- Mechanistic domains: 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 oral toxicity values for compounds of similar functionalities (saturated alkyl ethers) all fall to the “low persistence” category, 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.
- Other considerations (as appropriate):

6. ADEQUACY OF THE RESULT
6.1Regulatory 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, Authorisation and Restriction of Chemicals ("REAC H") and as required by Biocide Product Directive 98/8/EC ("98/8/EC")
6.2 Approach for regulatory interpretation of the model result
The predicted result has been presented in the formats directly usable for the intended regulatory purposes. The predicted numeric value in physicochemical units has been presented. The possible classification of the values according to classification systems has also been discussed.
6.3 Outcome
See section 3.2(e) for the classification of the prediction in light of the regulatory purpose described in 6.1.
6.4 Conclusion
Considering the above, the predicted result can be considered adequate for the regulatory conclusion described in 6.1.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2020

Report date:

2020

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD 309

Principles of method if other than guideline:

The half-life is the time required for the concentration of a substance to halve its original value in a particular environmental medium. The half-lives of organic compounds are among the most commonly used criteria for studying persistence [1]. The semiquantitative data based on expert judgment and actual experimental values have already been suggested by Webster et al. [2]. as preferable for half life identification, and are commonly used to develop the widely applied multimedia models [3,4]. In addition, a simple QSPR regression model has been demonstrated to be an useful tool for the identification and prioritization of existing or not yet synthesized potential persistent organic pollutants [5].
Endpoint units: The half-life values (in h) were transformed into logarhitmic form for modelling
Dependent variable: log T(0.5)
Experimental protocol: The dataset of structurally heterogeneous and highly representative of many classes of already defined problematic chemicals includes 206 organic compounds of known half-lives for transformation into air [6].

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

Results and discussion

% Degradation

Key result

Parameter:

half-life in days (QSAR/QSPR)

Value:

ca. 104

Remarks on result:

readily biodegradable based on QSAR/QSPR prediction

Details on results:

Simulation tests “attempt to simulate degradation in a specific environment by use of indigenous biomass, media, relevant solids […], and a typical temperature that represents the particular environment” (ECHA Guidance R.7b, version 1.2, November 2012).
In REACH it is specified that a simulation test (OECD 307/308/309) provides information on biodegradation under specified environmentally relevant conditions. The guidance states that where possible simulation studies should be conducted at environmentally relevant temperatures e.g. the temperature at which the environmental media was collected. However, it is recognized that it may not be practically possible to conduct the test at these environmental temperatures. In such cases attempts should be made to adapt the temperature as far as practically possible.
Key issue: In summary, REACH guidance recommends the Arrhenius equation to be applied to data obtained at 20o C to correct half-lives to environmentally relevant temperatures. It should not be used the other way around to predict a
half-life for 20o C. The temperature correction is not performed in a consistent way among the PBT-related frameworks
Key issue: As biodegradation is the most important removal process for many organic chemicals (in some cases it is the only relevant process) from the environment, and hence determines chemical persistence, lab-field extrapolation is an important topic. It should be noted that for other degradation processes like hydrolysis and photolysis, more opportunities are available to standardize test results and extrapolate these results to realistic field conditions.
Results from the OECD 301 screening test series do not give quantitative information on the rate of transformation / mineralization, not in a sewage treatment plant nor in the environment. Simulation tests like the OECD 308 and 309 tests, give a quantitative indication of environmental half lives in specific environmental compartments. Therefore a simulation test result by default will always overrule a OECD 301 ready biodegradability test result. A (single) negative test result in a ready biodegradability test can be overruled by positive results from other ready biodegradability tests, or inherent (OECD 302 series) or simulation tests. The reverse, i.e. a substance that is readily biodegradable, but still gives a very long half life in a simulation test, is also possible, although this is rarely observed. Such cases might be explained by the conditions in the ready biodegradability test that are not relevant for/representative of environmental conditions. In these cases (slow degradation in a simulation test of a ready biodegradable compound) the result of the simulation test should also be leading in the PBT assessment. This issue does not differ among PBT frameworks, although guidance on how to proceed with this is not always specifically provided.

Any other information on results incl. tables

Simulation test results always overrule ready biodegradability results in the assessment of persistency, independently of the scope of the framework. There is no unique persistence scale under REACH legislation. Different sources have used different scales, for instance according to Mackay, D., Shiu, W.Y., Ma, K.C. Physical-chemical properties and Environmental Fate Handbook, CRC, Chapman and Hall/CRC, Boca Raton, FL (USA), 2000, (http://files.rushim.ru/books/spravochniki/mackay3.pdf) the following persistence categories can be set:

	very high persistence	high persistence	medium persistence	low persistence
T0.5	T > 30000	3000 < T ≤ 30000	300 < T ≤ 3000	T ≤ 300

On the above scale, 3-(isodecyloxy)propylamine falls into the “medium persistence” category.

There is a REACH-related document: M. Scheringer, M. MacLeod, M. Matthies; Persistence Criteria in the REACH Legislation: Critical Evaluation and Recommendations, Final Report, 2006, which recommends an “OR” relationship to identify persistent compounds.

“A substance fulfils the persistence/vP criterion (P/vP) if .. .. the half-life in marine water is higher than 60 days, OR the half-life in fresh- or estuarine water is higher than 40/60 days

Applicant's summary and conclusion

Validity criteria fulfilled:

not specified

Interpretation of results:

readily biodegradable

Conclusions:

Following this classification, 3-(isodecyloxy)propylamine falls into the “medium persistence” category.

Executive summary:

Different sources have used different scales, for instance according to Mackay, D., Shiu, W.Y., Ma, K.C. Physical-chemical properties and Environmental Fate Handbook, CRC, Chapman and Hall/CRC, Boca Raton, FL (USA), 2000, (http://files.rushim.ru/books/spravochniki/mackay3.pdf) the following persistence categories can be set:

	very high persistence	high persistence	medium persistence	low persistence
T0.5	T > 30000	3000 < T ≤ 30000	300 < T ≤ 3000	T ≤ 300

On the above scale, 3-(isodecyloxy)propylamine falls into the “medium persistence” category.