3,3'-dimethylbiphenyl-4,4'-diyl diisocyanate

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

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

Justification for type of information:

The test substance TODI was found insoluble in water and its hydrolysis was found to be very fast and the 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).

Reference 2

Endpoint:

bioaccumulation in sediment species, other

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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.

Qualifier:

according to guideline

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

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.

Reference 3

Endpoint:

bioaccumulation in aquatic species, other

Type of information:

(Q)SAR

Adequacy of study:

supporting study

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.

Qualifier:

according to guideline

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

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.

Reference 4

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

experimental study

Adequacy of study:

supporting study

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

Qualifier:

according to guideline

Guideline:

other: Japan: Guidelines for Bioaccumulation Testing of Chemicals in fish

Deviations:

no

GLP compliance:

no

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
1^stconcentration area	19; 4.8	27; 26	17; 34	30; 14	20; 18
2^ndconcentration 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.