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Environmental fate & pathways

Biodegradation in water and sediment: simulation tests

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Endpoint:
biodegradation in water: simulation testing on ultimate degradation in surface water
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
see attached justification
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
biodegradation in water: ready biodegradability
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Principles of method if other than guideline:
Estimation of results of OECD screening tests on ready biodegradation in water: CATALOGIC (v5.11.5) BOD 28 days MITI (OECD 301C) v06.07
GLP compliance:
no
Oxygen conditions:
aerobic
Inoculum or test system:
activated sludge, domestic, non-adapted
Duration of test (contact time):
28 d
Parameter:
% degradation (O2 consumption)
Value:
ca. 32.35
Sampling time:
28 d
Details on results:
Model domain similarity:
- Parametric domain: 100%
- Structural domain: 61.54% (38.46% unknown)
- Mechanistic domain: 100%
Validity criteria fulfilled:
yes
Interpretation of results:
not readily biodegradable
Conclusions:
The test substance is not readily biodegradable (according to OECD criteria)
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
biodegradation in water: ready biodegradability
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model, but not (completely) falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Please refer to QMRF and QPRF in the section "Overall remarks" and "Executive summary", respectively.
Principles of method if other than guideline:
Prediction of ready biodegradability based on six QSAR models
GLP compliance:
no
Key result
Remarks on result:
other: Ready biodegradability prediction: Substance is not readily biodegradable.
Remarks on result:
other: Biowin1: Biodegrades Fast; Biowin2: Does Not Biodegrade Fast; Biowin3: Recalcitrant; Biowin4: Days; Biowin5: Does Not Biodegrade Fast; BIOWIN6: Does Not Biodegrade Fast

BIOWIN (v4.10) Program Results:

==============================

SMILES : CC(=O)C(N=Nc1c(ccc(c1)C(=O)OC)C(=O)OC)C(=O)Nc2ccc(cc2)NC(=O)C(N=Nc3c(

ccc(c3)C(=O)OC)C(=O)OC)C(=O)C

MOL FOR: C34 H32 N6 O12

MOL WT : 716.67

--------------------------- BIOWIN v4.10 Results ----------------------------

Biowin1 (Linear Model Prediction)   : Biodegrades Fast

Biowin2 (Non-Linear Model Prediction): Does Not Biodegrade Fast

Biowin3 (Ultimate Biodegradation Timeframe): Recalcitrant

Biowin4 (Primary Biodegradation Timeframe): Days

Biowin5 (MITI Linear Model Prediction)   : Does Not Biodegrade Fast

Biowin6 (MITI Non-Linear Model Prediction): Does Not Biodegrade Fast

Biowin7 (Anaerobic Model Prediction): Does Not Biodegrade Fast

Ready Biodegradability Prediction: NO

 

 

Type

Num

Biowin1 Fragment description

Coeff

Value

Frag

4

Ester  [-C(=O)-O-C]

0.1742

0.6967

Frag

2

Amide  [-C(=O)-N or -C(=S)-N]

0.2102

0.4203

Frag

2

Ketone  [-C-C(=O)-C-]

0.0068

0.0137

Frag

2

Azo group  [-N=N-]

-0.2418

-0.4837

MolWt

*

Molecular Weight Parameter

-0.3412

Const

*

Equation Constant

0.7475

Result

Biowin1 (Linear Biodeg Probability)

1.0534

Type

Num

Biowin2 Fragment description

Coeff

Value

Frag

4

Ester  [-C(=O)-O-C]

4.0795

16.3180

Frag

2

Amide  [-C(=O)-N or -C(=S)-N]

2.6913

5.3826

Frag

2

Ketone  [-C-C(=O)-C-]

-0.4530

-0.9060

Frag

 2

Azo group  [-N=N-]

-8.2194

-16.4388

MolWt

*

Molecular Weight Parameter

 

-10.1767

Result

Biowin2 (Non-Linear Biodeg Probability)

0.0567

A probability greater than or equal to 0.5 indicates --> biodegrades fast

A probability less than 0.5 indicates --> does not biodegrade fast

 

Type

Num

Biowin3 Fragment description

Coeff

Value

Frag

4

Ester  [-C(=O)-O-C]

0.1402

0.5608

Frag

2

Amide  [-C(=O)-N or -C(=S)-N]

-0.0542

-0.1084

Frag

2

Ketone  [-C-C(=O)-C-]

-0.0225

-0.0450

Frag

 2

Azo group  [-N=N-]

-0.3004

-0.6007

MolWt

*

Molecular Weight Parameter

 

-1.5837

Const

*

Equation Constant

 

3.1992

Result

Biowin3 (Survey Model - Ultimate Biodeg)

1.4222

 

Type

Num

Biowin4 Fragment description

Coeff

Value

Frag

4

Ester  [-C(=O)-O-C]

0.2290

0.9158

Frag

2

Amide  [-C(=O)-N or -C(=S)-N]

0.2054

0.4109

Frag

2

Ketone  [-C-C(=O)-C-]

-0.0222

-0.0444

Frag

 2

Azo group  [-N=N-]

-0.0528

-0.1056

MolWt

*

Molecular Weight Parameter

 

-1.0340

Const

*

Equation Constant

 

3.8477

Result

Biowin4 (Survey Model - Primary Biodeg)

3.9904

Result classification: 5.00 -> hours 4.00 -> days 3.00 -> weeks

(primary & ultimate) 2.00 -> months 1.00 -> longer

 

Type

Num

Biowin5 Fragment description

Coeff

Value

Frag

4

Ester  [-C(=O)-O-C]

0.3437

1.3749

Frag

2

Amide  [-C(=O)-N or -C(=S)-N]

0.1266

0.2533

Frag

2

Ketone  [-C-C(=O)-C-]

0.1177

0.2355

Frag

2

Azo group  [-N=N-]

-0.0459

-0.0917

Frag

10

Aromatic-H

0.0082

0.0822

Frag

6

Methyl [-CH3]

0.0004

0.0025

Frag

2

-CH- [linear]

-0.0507

-0.1013

MolWt

*

Molecular Weight Parameter

 

-2.1321

Const

*

Equation Constant

 

0.7121

Result

Biowin5 (MITI Linear Biodeg Probability)

0.3353

 

Type

Num

Biowin6 Fragment description

Coeff

Value

Frag

4

Ester  [-C(=O)-O-C]

2.4462

9.7846

Frag

2

Amide  [-C(=O)-N or -C(=S)-N]

0.8859

1.7717

Frag

2

Ketone  [-C-C(=O)-C-]

0.8334

1.6669

Frag

2

Azo group  [-N=N-]

-10.6129

-21.2258

Frag

10

Aromatic-H

0.1201

1.2014

Frag

6

Methyl [-CH3]

0.0194

0.1166

Frag

2

-CH- [linear]

-0.0998

-0.1995

MolWt

*

Molecular Weight Parameter

 

-20.6893

Result

Biowin6 (MITI Non-Linear Biodeg Probability)

0.0000

A probability greater than or equal to 0.5 indicates --> readily degradable

A probability less than 0.5 indicates --> not readily degradable

 

Validity criteria fulfilled:
yes
Interpretation of results:
not readily biodegradable
Executive summary:

QPRF: BIOWIN v4.10

 

1.

Substance

See “Test material identity”

2.

General information

 

2.1

Date of QPRF

See “Data Source (Reference)”

2.2

QPRF author and contact details

See “Data Source (Reference)”

3.

Prediction

3.1

Endpoint
(OECD Principle 1)

Endpoint

Biodegradability

Dependent variable

Biodegradability

3.2

Algorithm
(OECD Principle 2)

Model or submodel name

BIOWIN

Model version

v. 4.10

Reference to QMRF

QMRF: Estimation of Aerobic Biodegradability using BIOWIN v4.10 (EPI Suite v4.11): BIOWIN1 to BIOWIN6 and Ready Biodegradability Prediction

Predicted value (model result)

See “Results and discussion”

Input for prediction

- Chemical structure via CAS number or SMILES

Descriptor values

- Structure fragments

- Molecular weight

3.3

Applicability domain
(OECD principle 3)

Domains (Appendix D, On-Line BIOWIN User’s Guide):

1) Molecular weight

See below (Assessment of estimation domain)

2) Fragments:

See below (Assessment of estimation domain)

3.4

The uncertainty of the prediction
(OECD principle 4)

Parameter

BIOWIN model

1

2

3

4

5

6

Total correct

264 / 295

275 / 295

167 / 200

165 / 200

485 / 589

488 / 589

% correct, total

89.5

93.2

83.5

82.5

82.3

82.9

% correct, fast

97.3 (181 / 186)

97.3 (181 / 186)

93.5 (101 / 108)

84.9 (101 / 119)

79.1 (201 / 254)

80.3 (204 / 254)

3.5

The chemical mechanisms according to the model underpinning the predicted result
(OECD principle 5)

The chemical structure influences the biodegradability of the substance. Therefore, chemical fragments were selected having a potential effect on biodegradability. In order to be able to predict the biodegradability probability of substances without these specific fragments, the molecular weight was integrated into the models.

 

References

- US EPA (2012). On-Line BIOWIN User’s Guide.

 

 

Assessment of estimation domain (molecular weight, fragments):

 

Model:

BIOWIN v4.10

 

Substance:

tetramethyl 2,2'-{1,4-phenylenebis[imino(1,3-dioxobutane-2,1-diyl)diazene-2,1-diyl]}diterephthalate

CAS-#:

68516-73-4

SMILES:

CC(=O)C(N=Nc1c(ccc(c1)C(=O)OC)C(=O)OC)C(=O)Nc2ccc(cc2)NC(=O)C(N=Nc3c(
ccc(c3)C(=O)OC)C(=O)OC)C(=O)C

Molecular weight (g/mol):

716.67

 

AppendixD - Fragment Coefficients for Biodegradation Models

 

BIOWIN1 and BIOWIN2: Linear / Non-Linear Biodegradability

Fragment description

Coefficient

 

Training set fragment count

No. of instances
of each bond
found for the
current substance

 

Linear

Non-linear

Min

Max

No. of compounds in training set containing the fragment

Ester [-C(=O)-O-C]

0.17418

4.0795

-

3

23

4

Amide [-C(=O)-N or -C(=S)-N]

0.21015

2.6913

-

1

12

2

Ketone [-C-C(=O)-C-]

0.00683

-0.453

-

2

12

2

Azo group [-N=N-]

-0.24183

-8.2194

-

1

2

2

Molecular Weight

---

---

31.06

697.7

 

out of range

 

BIOWIN3 and BIOWIN4: Ultimate / Primary biodegradability

Fragment description

Coefficient

 

Training set fragment count

No. of instances
of each bond
found for the
current substance

 

Ultimate

Primary

Min

Max

No. of compounds in training set containing the fragment

Ester [-C(=O)-O-C]

0.14021

0.22896

-

4

25

4

Amide [-C(=O)-N or -C(=S)-N]

-0.05421

0.20543

-

1

13

2

Ketone [-C-C(=O)-C-]

-0.02248

-0.02222

-

4

10

2

Azo group [-N=N-]

-0.30036

-0.05279

-

1

3

2

Molecular Weight

---

---

53.06

697.65

-

out of range

 

BIOWIN5 and BIOWIN6: MITI Biodegradability Coefficients (Linear / Non-Linear)

Fragment description

Coefficient

 

Training set fragment count

No. of instances
of each bond
found for the
current substance

 

Linear

Non-Linear

Min

Max

No. of compounds in training set containing the fragment

Ester [-C(=O)-O-C]

0.343735

2.44616254

 -

3

46

4

Amide [-C(=O)-N or -C(=S)-N]

0.126629

0.88586757

 -

2

24

2

Ketone [-C-C(=O)-C-]

0.117739

0.83343688

 -

2

25

2

Azo group [-N=N-]

-0.045873

-10.6129184

 -

1

2

2

Aromatic-H

0.008218

0.12014128

 -

15

302

10

Methyl [-CH3]

0.000411

0.01942827

 -

9

295

6

-CH- [linear]

-0.050672

-0.09977022

 -

4

63

2

Molecular Weight

 ---

---

30.02

959.2

-

in range

 

Fragment description

Coefficient

 

Min

Max

No. of compounds in training set containing the fragment

No. of instances
of each bond
found for the
current substance

Molecular Weight

---

---

46.07

885.46

 

in range

 

Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
additional information on environmental fate and behaviour
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2021
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
other: OECD 318

At any of the time points mentioned in the TG-318, the influence of Ca is critical. Regardless of pH, the pigment is unstable in 10 mM Ca, representing high water hardness.


After 6h, the samples showed high dispersion stability in 0 mM Ca and on a lower level intermediate stability in 1 mM and 10 mM Ca.


After 24 hours the stability in 0 mM Ca became intermediate. For the samples in 1 and 10 mM Ca the stability was low.




















































































































































Full results of the dispersion stability in the presence of NOM
 Ca(NO3)2Stability after 6hStandard deviationStability after 15hStandard deviationStability after 24hStandard deviation
 [mM][%][%][%][%][%][%]
        
pH 4091.22.778.44.564.74.5
pH 4116.21.55.80.32.90.4
pH 41011.50.74.10.62.90.8
.       
pH 7089.40.973.51.260.11.3
pH 7113.60.54.60.42.80.4
pH 71012.71.34.90.42.90.4
.       
pH 90940.284.50.771.51
pH 9113.90.95.30.53.80.4
pH 91011.50.85.70.24.60.1

 


 


To rationalize the observed dispersion stability, we finally checked the particle size distribution directly in the environmental medium. We applied the NanoDefine method of Analytical Ultracentrifugation. The centrifugation parameters are given in the methods section.


As required by TG318, paragraph 31, the tested nanomaterial was pre-wetted in ultrapure water and left in the form of wet-paste for 24 h. The TG318 requires this step “to insure the proper interaction of nanomaterial surface with ultrapure water.” We visually observed incomplete wetting, and so any ensuing measurement would have been incorrect. In accord with the NanoGenoTox dispersion protocol, a drop of ethanol was added, successfully transferred the powder into a paste, which was then further diluted as specified in the TG318


The observed size distributions confirm the moderate agglomeration at 1 mM Ca, pH7, with NOM. If the particles would have been significantly dissolved, no size distribution would be observable at all by this method, which relies on the detection of the movement of particles during centrifugal separation.


Additionally, the centrifugation methods include a determination of the remaining absorption after centrifugation, fully consistent with the conventional determination of the dissolved fraction after centrifugation as recommended by the TG-318. The remaining absorption was measured at ca. 0.02. This is a fraction of 1% of the initial absorption, but actually is close to the LOD of the built-in UV/Vis detector. Considering the LOD, between 0% and 2% of the sample may have been dissolved.


All evidence combined, the results after centrifugation confirm that at least 98% of the observed dispersion stability has to be attributed to the particles, not to dissolution.

Executive summary:

At any of the time points mentioned in the TG-318, the influence of Ca is critical. Regardless of pH, the pigment is unstable in 10 mM Ca, representing high water hardness.


After 6h, the samples showed high dispersion stability in 0 mM Ca and on a lower level intermediate stability in 1 mM an 10 mM Ca.


After 24 hours the stability in 0 mM Ca became intermediate. For the samples in 1 and 10 mM Ca the stability was low.

Reason / purpose for cross-reference:
data waiving: supporting information
Reference

At any of the time points mentioned in the TG-318, the influence of Ca is critical. Regardless of pH, the pigment is unstable in 10 mM Ca, representing high water hardness.


After 6h, the samples showed high dispersion stability in 0 mM Ca and on a lower level intermediate stability in 1 mM an 10 mM Ca.


After 24 hours the stability in 0 mM Ca became intermediate. For the samples in 1 and 10 mM Ca the stability was low.

Data source

Materials and methods

Results and discussion

Transformation products:
no
Remarks:
Since the substance is highly insoluble in water, simulation biodegradation tests in water and sediment are not proposed, since no relevant new findings are expected from such investigations.

Applicant's summary and conclusion