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Bioaccumulation: aquatic / sediment

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Endpoint:
bioaccumulation in aquatic species: fish
Data waiving:
other justification
Justification for data waiving:
the study does not need to be conducted because the substance has a low potential to cross biological membranes
the study does not need to be conducted because direct and indirect exposure of the aquatic compartment to the substance is unlikely
other:
Endpoint:
bioaccumulation in sediment species, other
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 and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Reference:
Composition 1
Composition 2
Composition 3
Qualifier:
according to
Guideline:
other: REACH Guidance on QSAR R.6
Principles of method if other than guideline:
Estimation of BCF, BAF and biotransformation rate using BCFBAF v3.01
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: Nc(c(cc(c(ccc(N)c1C)c1)c2)C)c2
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on calculated log Pow of: 2.34 (Exper. database match, Ref: HANSCH,C ET AL. (1995))
Key result
Type:
BCF
Value:
16.25 L/kg
Basis:
whole body w.w.
Remarks on result:
other: QSAR predicted value. The substance is within the applicability domain of the model.
Key result
Type:
BCF
Value:
47 L/kg
Remarks on result:
other: Experimental Database Structure Match value.
Details on kinetic parameters:
Biotransformation half-life (days): 0.203 (normalized to 10 g fish at 15°C)
Biotransformation rate (kM, normalized to 10 g fish): 3.411/day

BCFBAF Program (v3.01) Results:

 

SMILES : Nc(c(cc(c(ccc(N)c1C)c1)c2)C)c2

CHEM  :

MOL FOR: C14 H16 N2

MOL WT : 212.30

 

Summary Results:

 Log BCF (regression-based estimate): 1.21 (BCF = 16.3 L/kg wet-wt)

 Biotransformation Half-Life (days) : 0.203 (normalized to 10 g fish)

 Log BAF (Arnot-Gobas upper trophic): 1.25 (BAF = 17.7 L/kg wet-wt)

 

Experimental BCF-kM Database Structure Match:

 

 Name     : [1,1-Biphenyl]-4,4-diamine, 3,3-dimethyl-

 CAS Num  : 000119-93-7

 Log BCF  : 1.6721 (BCF = 47 L/kg wet-wt)

 BCF Data : BCF NonIonic Training Set

 Log Bio HL: ---

 Bio Data : ---

 

Log Kow (experimental): 2.34

Log Kow used by BCF estimates: 2.34

 

Equation Used to Make BCF estimate:

  Log BCF = 0.6598 log Kow - 0.333 + Correction

 

     Correction(s):                   Value

      No Applicable Correction Factors

 

  Estimated Log BCF = 1.211 (BCF = 16.25 L/kg wet-wt)

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

Type

NUM

LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION

COEFF

VALUE

FRAG

2

Aromatic amine  [-NH2 or -NH-]

-0.2890

-0.5779

FRAG

2

Alkyl substituent on aromatic ring

0.1781

0.3561

FRAG

2

                             Aromatic-CH3

-0.0872

-0.1743

FRAG

6

Aromatic-H

0.2664

1.5983

FRAG

1

Biphenyl

-0.5319

-0.5319

L KOW

*

Log Kow =  2.34 (experimental  )

0.3073

0.7192

MOLWt

*

Molecular Weight Parameter   

 

-0.5444

CONST

*

Equation Constant

 

-1.5371

RESULT

 

LOG Bio Half-Life (days)

 

-0.6921

RESULT

 

Bio Half-Life (days)

 

0.2032

NOTE

 

Bio Half-Life Normalized to 10 g fish at 15 deg C

 

 

 

Biotransformation Rate Constant:

 kM (Rate Constant): 3.411 /day (10 gram fish)

 kM (Rate Constant): 1.918 /day (100 gram fish)

 kM (Rate Constant): 1.079 /day (1 kg fish)

 kM (Rate Constant): 0.6066 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

  Estimated Log BCF (upper trophic) = 1.248 (BCF = 17.69 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 1.248 (BAF = 17.69 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 1.133 (BCF = 13.6 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 1.133 (BAF = 13.6 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 1.092 (BCF = 12.37 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 1.092 (BAF = 12.37 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

  Estimated Log BCF (upper trophic) = 1.385 (BCF = 24.28 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 1.402 (BAF = 25.22 L/kg wet-wt)

 

 

 

 

Validity criteria fulfilled:
yes
Conclusions:
Using BCFBAF v3.01 the BCF value of the test item was calculated to be 16.25 L/kg. The substance is within the applicability domain of the model.
Executive summary:

The BCF value was calculated using BCFBAF v3.01 as part of EPISuite v4.11 from US Environmental Protection Agency. The BCF value of the test item was calculated to be 16.25 L/kg at 25 °C (EPI Suite, 2014). Additionally, the experimental BCF value is 47 L/kg wet/wet (Database Struture Match).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model isapplicable to thequery chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model isrelevant for theregulatory purpose.

 

For assessment and jsutification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Endpoint:
bioaccumulation in aquatic species, other
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 and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
Please refer to the QMRF and QPRF files provided under the section attached justification.
Reference:
Composition 1
Composition 2
Composition 3
Qualifier:
according to
Guideline:
other: REACH Guidance on QSAR R.6
Principles of method if other than guideline:
Estimation of BCF, BAF and biotransformation rate using BCFBAF v3.01
GLP compliance:
no
Test material information:
Composition 1
Specific details on test material used for the study:
SMILES: O=C=N/c1ccc(cc1C)c2ccc(\N=C=O)c(C)c2
Test organisms (species):
other: fish
Details on estimation of bioconcentration:
BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01
- Result based on calculated log Pow of: 6.05
Key result
Temp.:
15 °C
Type:
BCF
Value:
4 569 L/kg
Basis:
not specified
Remarks on result:
other: QSAR predicted value. The substance is within the applicability domain of the model.
Details on kinetic parameters:
Biotransformation half-life (days): 7.82 (normalized to 10 g fish at 15°C)
Biotransformation rate (kM, normalized to 10 g fish): 0.08863/day

BCFBAF Program (v3.01) Results:

 

SMILES : O=C=Nc1ccc(cc1C)c2ccc(N=C(=O))c(C)c2

MOL FOR: C16 H12 N2 O2

MOL WT : 264.29

 

Log BCF (regression-based estimate): 3.66 (BCF = 4.57e+003 L/kg wet-wt)

Biotransformation Half-Life (days) : 7.82 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 3.95 (BAF = 8.99e+003 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 6.05

 

Equation Used to Make BCF estimate:

Log BCF = 0.6598 log Kow - 0.333 + Correction

 

Correction(s): No Applicable Correction Factors

 

Estimated Log BCF = 3.660 (BCF = 4569 L/kg wet-wt)

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

Type

NUM

LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION

COEFF

VALUE

FRAG

2

Alkyl substituent on aromatic ring

0.1781

0.3561

FRAG

2

 Aromatic-CH3

-0.0872

-0.1743

FRAG

6

Aromatic-H

0.2664

1.5983

FRAG

1

Biphenyl

-0.5319

-0.5319

L KOW

*

Log Kow = 6.05 (KowWin estimate)

0.3073

1.8599

MOLWt

*

Molecular Weight Parameter

 

-0.6777

CONST

*

Equation Constant

 

-1.5371

RESULT

 

LOG Bio Half-Life (days)

 

0.8933

RESULT

 

Bio Half-Life (days)

 

7.821

NOTE

 

Bio Half-Life Normalized to 10 g fish at 15 deg C

 

 

 

Biotransformation Rate Constant:

 kM (Rate Constant): 0.08863 /day (10 gram fish)

 kM (Rate Constant): 0.04984 /day (100 gram fish)

 kM (Rate Constant): 0.02803 /day (1 kg fish)

 kM (Rate Constant): 0.01576 /day (10 kg fish)

 

Arnot-Gobas BCF & BAF Methods (including biotransformation rate estimates):

  Estimated Log BCF (upper trophic) = 3.378 (BCF = 2389 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 3.954 (BAF = 8986 L/kg wet-wt)

  Estimated Log BCF (mid trophic)  = 3.511 (BCF = 3241 L/kg wet-wt)

  Estimated Log BAF (mid trophic)  = 4.295 (BAF = 1.972e+004 L/kg wet-wt)

  Estimated Log BCF (lower trophic) = 3.549 (BCF = 3539 L/kg wet-wt)

  Estimated Log BAF (lower trophic) = 4.505 (BAF = 3.201e+004 L/kg wet-wt)

 

Arnot-Gobas BCF & BAF Methods (assuming a biotransformation rate of zero):

  Estimated Log BCF (upper trophic) = 4.321 (BCF = 2.096e+004 L/kg wet-wt)

  Estimated Log BAF (upper trophic) = 6.468 (BAF = 2.939e+006 L/kg wet-wt)

 

Validity criteria fulfilled:
yes
Conclusions:
Using BCFBAF v3.01 the BCF value of the test item was calculated to be 4569 L/kg at 25 °C. The substance is within the applicability domain of the model.
Executive summary:

The BCF value was calculated using BCFBAF v3.01 as part of EPISuite v4.11 from US Environmental Protection Agency. The BCF value of the test item was calculated to be 4569 L/kg at 25°C (EPI Suite, 2014).

The adequacy of a prediction depends on the following conditions:

a) the (Q)SAR model is scientifically valid: the scientific validity is established according to the OECD principles for (Q)SAR validation;

b) the (Q)SAR model isapplicable to thequery chemical: a (Q)SAR is applicable if the query chemical falls within the defined applicability domain of the model;

c) the (Q)SAR result is reliable: a valid (Q)SAR that is applied to a chemical falling within its applicability domain provides a reliable result;

d) the (Q)SAR model isrelevant for theregulatory purpose.

 

For assessment and jsutification of these 4 requirements the QMRF and QPRF files were developed and attached to this study record.

 

Description of the prediction Model

The prediction model was descripted using the harmonised template for summarising and reporting key information on (Q)SAR models. For more details please refer to the attached QSAR Model Reporting Format (QMRF) file. 

 

Assessment of estimation domain

The assessment of the estimation domain was documented in the QSAR Prediction Reporting Format file (QPRF). Please refer to the attached document for the details of the prediction and the assessment of the estimation domain.

Endpoint:
bioaccumulation in aquatic species: fish
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1983-05-14 to 1984-01-9
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods
Reference:
Composition 1
Qualifier:
according to
Guideline:
other: Japan: Guidelines for Bioaccumulation Testing of Chemicals in fish
Deviations:
no
GLP compliance:
no
Test material information:
Composition 1
Radiolabelling:
no
Vehicle:
yes
Test organisms (species):
Cyprinus carpio
Route of exposure:
aqueous
Test type:
flow-through
Water / sediment media type:
natural water: freshwater
Total exposure / uptake duration:
> 0 - < 8 wk
Nominal and measured concentrations:
Nominal: 200 µg/L; 20 µg/L
Measured (average value): 186 µg/L (after 8 weeks); 16.8 µg/L (after 8 weeks)
Details on estimation of bioconcentration:
Each of fish and test water was sampled and analyzed at five points (2, 3, 4, 6 and 8 weeks). Fish body was pretreated and the concentration of TODA in the fish was analyzed by HPLC. Test water was pretreated and the concentration of TODA in the water was analyzed by HPLC. BCF was calculated from the ratio of the concentration of TODA in the fish to the concentration of TODA in the water.
Key result
Conc. / dose:
0.2 mg/L
Type:
BCF
Value:
> 4.8 - < 34 dimensionless
Basis:
whole body w.w.
Calculation basis:
steady state
Key result
Conc. / dose:
0.02 mg/L
Type:
BCF
Value:
> 10 - < 83 dimensionless
Basis:
whole body w.w.
Calculation basis:
steady state

BCF for TODA

   2 weeks  3 weeks 4 weeks  6 weeks  8 weeks 
 1stconcentration area  19; 4.8 27; 26   17; 34  30; 14  20; 18
 2ndconcentration area  43; (36)  62;54  67; 83  (32); (29)  (21); (10)
           
Validity criteria fulfilled:
yes
Conclusions:
For either nominal concentration (0.2 mg/L and 0.02 mg/L) the BCF was determined to be below 100 and thus TODA is not considered to have a bioaccumulation potential.
Executive summary:

In a flow-through bioaccumulation study in freshwater with carp (species: Cyprinus carpio) carried out according to the Japanese Guideline for Bioaccumulation Testing of Chemicals in Fish, no bioaccumulation potential of the degradation product of TODI, TODA, was observed. The BCF values were determined to be below 100. For the concentration of 0.2 mg TODA / L a BCF of > 4.8 to <34 was determined. For the concentration of 0.02 mg TODA / L a BCF > 10 to < 83 was determined.

Description of key information

In accordance with column 2 of REACH 1907/2006/EC Annex IX, section 9.3.2, a bioaccumulation test in aquatic species does not need to be conducted as
- the direct and indirect exposure of aquatic compartment is unlikely
- TODI was found insoluble in water (thus uptake into biological cells is very unlikely)
- TODI did not reveal aquatic toxicity at concentrations below water solubility
- TODI’s hydrolysis was found to be very fast
- TODI’s degradation product was found to be insoluble in organic and aqueous solvents (See IUCLID sections 6.1.1, short-term toxicity to fish and 6.1.3, short-term toxicity to aquatic invertebrate)
- For TODI’s degradation product TODA the measured BCF was below 100 (0.2 mg/L: 4.8 - 34; 0.02 mg/L: 10-83) and the estimated BCF was 16.25 L/kg wet-wt.
Thus, based on the fast hydrolysis of TODI (The t1/2 at pH 4 and 9, at 25 and 50 °C was lower than or equal as 2 minutes; at pH7 the t1/2 was 16 hours and 1.2 hours at 25 and 50 °C respectively.)  and the low BCF value of the degradation product TODA, bioaccumulation of the environmentally relevant degradation product TODA is considered negligible and no further information concerning bioconcentration or bioaccumulation for TODI is required.

 

Key value for chemical safety assessment

Additional information