3-aminomethyl-3,5,5-trimethylcyclohexylamine

Bioaccumulation: aquatic / sediment

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

according to the model's AD index, the substance could be out of the applicability domain of the model.

Justification for type of information:

1. SOFTWARE
VEGA platform v1.1.3

2. MODEL (incl. version number)
BCF (KNN/Read Across) v1.1.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

The model performs a read-across and provides a quantitative prediction of bioconcentration factor (BCF) in fish, given in log(L/kg). The read-across is based on the similarity index developed inside the VEGA platform; the index takes into account several structural aspects of the compounds, such as their fingerprint, the number of atoms, of cycles, of heteroatoms, of halogen atoms, and of particular fragments (such as nitro groups). On the basis of this structural similarity index, the three compounds from the dataset resulting most similar to the chemical to be predicted are taken into account: the estimated BCF value is calculated as the weighted average value of the experimental values of the three selected compounds, using their similarity values as weight.

GLP compliance:

no

Specific details on test material used for the study:

- SMILES code: NCC(CC(N)CC1(C)C)(C1)C

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: BCF model (Read-Across/KNN) v1.1.0 implemented in VEGA v1.1.3

Key result

Type:

BCF

Value:

2.63 L/kg

Remarks on result:

other: according to the model's AD index, the substance could be out of the applicability domain of the model. An expert analysis can be found in chapter "Administrative Data, Attached justification".

Type:

other: log BCF

Value:

0.42 other: log (L/kg)

Remarks on result:

other: according to the model's AD index, the substance could be out of the applicability domain of the model. An expert analysis can be found in chapter "Administrative Data, Attached justification".

Reference 2

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2016

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

Remarks:

According to the model’s global AD index, the predicted substance is not within the applicability domain of the model.

Justification for type of information:

1. SOFTWARE
VEGA platform v1.1.3

2. MODEL (incl. version number)
BCF model (CAESAR) v2.1.14

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

The BCF is estimated based on several molecular descriptors.
The applicability domain of predictions is assessed using an Applicability Domain Index (ADI) calculated by grouping several other indices, e.g. by a similarity index that consider molecule's fingerprint and structural aspects (count of atoms, rings and relevant fragments).

GLP compliance:

no

Specific details on test material used for the study:

- SMILES code: NCC(CC(N)CC1(C)C)(C1)C

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: VEGA CAESAR v2.1.14 implemented in the VEGA tool v.1.1.3 (calculation core: v1.2.2)
- Result based on calculated log Pow of 1.62 (calculated by VEGA: MLogP)

Key result

Type:

BCF

Value:

3 L/kg

Remarks on result:

other: According to the model’s global AD index, the predicted substance is not within the applicability domain of the model. An expert analysis can be found in chapter "Administrative Data, Attached justification" (see attached QPRF documents).

Type:

other: log BCF

Value:

0.49 other: log(L/kg)

Remarks on result:

other: According to the model’s global AD index, the predicted substance is not within the applicability domain of the model. An expert analysis can be found in chapter "Administrative Data, Attached justification" (see attached QPRF documents).

Reference 3

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

Scientifically accepted calculation method. The substance is entirely within the applicability domain (AD) of the submodel according to Meylan et al. (1997/1999), but the calculation methods according to Arnot & Gobas (2003) and Arnot et al. (2008) may be less accurate, due to the substance's property to appreciably ionize at physiological pH. According to the submodel Arnot et al. (2008), the substance is not within the applicability domain of the submodel, as the maximum number of instances of biotransformation fragments is exceeded.

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) for the uncharged molecule at 25 °C as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

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 code: NCC(CC(N)CC1(C)C)(C1)C

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: measured

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01 (EPI Suite v4.11)
- Result based on measured log Pow of: 0.99 (Hüls Infracor GmbH 1998, report no. AN_ASB 0093)

Key result

Type:

BCF

Value:

3.16 L/kg

Basis:

not specified

Remarks on result:

other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).

Key result

Type:

BCF

Value:

1.872 L/kg

Basis:

not specified

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Key result

Type:

BCF

Value:

1.938 L/kg

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

1.872 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

1.953 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Details on kinetic parameters:

Biotransformation half-life (days): 0.405
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): 1.709 / day
The substance is not within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b), as the substance appreciably ionizes at physiologically relevant pH. In addition, the maximum number of instances of biotransformation fragments is exceeded.

Summary Results:

Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)

Biotransformation Half-Life (days) : 0.405 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 0.27 (BAF = 1.87 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 0.99 (user entered)

 

Equation Used to Make BCF estimate:

Log BCF = 0.50

 

Correction(s):                   Value

Correction Factors Not Used for Log Kow < 1

 

Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)

 

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

TYPE	NUM	LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	2	Carbon with 4 single bonds & no hydrogens	-0.2984	-0.5969
Frag	2	Aliphatic amine  [-NH2 or -NH-]	0.4067	0.8135
Frag	3	Methyl [-CH3]	0.2451	0.7353
Frag	1	-CH2- [linear]	0.0242	0.0242
Frag	3	-CH2- [cyclic]	0.0963	0.2888
Frag	1	-CH - [cyclic]	0.0126	0.0126
L Kow	*	Log Kow =  0.99 (user-entered  )	0.3073	0.3043
MolWt	*	Molecular Weight Parameter		-0.4367
Const	*	Equation Constant		-1.5371
RESULT	LOG Bio Half-Life (days)			-0.3920
RESULT	Bio Half-Life (days)			0.4055
NOTE	Bio Half-Life Normalized to 10 g fish at 15 deg C

 

Biotransformation Rate Constant:

kM (Rate Constant): 1.709 /day (10 gram fish)

kM (Rate Constant): 0.9613 /day (100 gram fish)

kM (Rate Constant): 0.5406 /day (1 kg fish)

kM (Rate Constant): 0.304 /day (10 kg fish)

 

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

Estimated Log BCF (upper trophic) = 0.272 (BCF = 1.872 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 0.272 (BAF = 1.872 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 0.199 (BCF = 1.58 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 0.199 (BAF = 1.58 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 0.179 (BCF = 1.51 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 0.179 (BAF = 1.51 L/kg wet-wt)

 

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

Estimated Log BCF (upper trophic) = 0.287 (BCF = 1.938 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 0.291 (BAF = 1.953 L/kg wet-wt)

Reference 4

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

Based on the mean absolute errors of the models the confidence in the predicted results is high (except for the model Group contribution, where the confidence in the predicted results is low).

Justification for type of information:

1. SOFTWARE
T.E.S.T. (version 4.2.1) (Toxicity Estimation Software Tool). US EPA, 2012.

2. MODEL (incl. version number)
T.E.S.T. (version 4.2.1); BCF model

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QPRF).
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

T.E.S.T. is a toxicity estimation software tool. The program requires only the molecular structure of the test item, all other molecular descriptors which are required to estimate the toxicity are calculated within the tool itself. The molecular descriptors describe physical characteristics of the molecule (e.g. E-state values and E-state counts, constitutional descriptors, topological descriptors, walk and path counts, connectivity, information content, 2d autocorrelation, Burden eigenvalue, molecular property (such as the octanol-water partition coefficient), Kappa, hydrogen bond acceptor/donor counts, molecular distance edge, and molecular fragment counts). Each of the available methods uses a different set of these descriptors to estimate the toxicity.
The bioaccumulation factor (BCF) was estimated using several available methods: hierarchical clustering method; FDA method, single model method; group contribution method; nearest neighbour method; consensus method. The methods were validated using statistical external validation using separate training and test data sets.
The experimental data set was obtained from several different databases (Dimitrov et al., 2005; Arnot and Gobas, 2006; EURAS; Zhao, 2008). From the available data set salts, mixtures and ambiguous compounds were removed. The final data set contained 676 chemicals.

References:
- Dimitrov, S., N. Dimitrova, T. Parkerton, M. Combers, M. Bonnell, and O. Mekenyan. 2005. Base-line model for identifying the bioaccumulation potential of chemicals. SAR and QSAR in Environmental Research 16:531-554.
- Arnot, J.A., and F.A.P.C. Gobas. 2006. A review of bioconcentration factor (BCF) and bioaccumulation factor (BAF) assessments for organic chemicals in aquatic organisms. Environ. Rev. 14:257-297.
- EURAS. Establishing a bioconcentration factor (BCF) Gold Standard Database. EURAS [cited 5/20/09]. Available from http://www.euras.be/eng/project.asp?ProjectId=92.
- Zhao, C.; Boriani, E.; Chana, A.; Roncaglioni, A.; Benfenati, E. 2008. A new hybrid system of QSAR models for predicting bioconcentration factors (BCF). Chemosphere 73:1701-1707.

GLP compliance:

no

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: US EPA T.E.S.T. v4.2.1

Applied estimation methods:
- Hierarchical clustering
- FDA
- Single model
- Group contribution
- Nearest neighbour
- Consensus

Key result

Type:

BCF

Value:

9.3 L/kg

Remarks on result:

other: method: consensus (average of reasonable results from all models); log BCF = 0.97; Based on the mean absolute error, the confidence in the predicted BCF values is high.

Model details:

Method	Predicted value		Model statistics			MAE (in log10)
						External test set		Training set
	log BCF	BCF	r²	q²	No. of chemicals	Entire set	SC >= 0.5	Entire set	SC >= 0.5
Consensus method	0.97	9.28	-	-	-	0.51	0.50	0.42	0.32
Hierarchical clustering	0.83	6.83 (3.07-15.19)	0.748 - 0.894	0.651 - 0.869	34 - 540 (cluster models: 8)	0.54	0.50	0.23	0.03
Single model	1.50	31.29 (2.32-421.30)	0.764	0.733	540	0.54	0.50	0.53	0.48
Group contribution	1.14	13.90 (0.44-443.81)	0.719	0.527	499	0.62	0.50	0.60	0.73
FDA	1.05	11.31 (1.19-107.23)	0.898	0.824	30	0.57	0.50	0.53	0.40
Nearest neighbour	0.31	2.05	-	-	3	0.60	0.50	0.55	0.26

 

Legend:

MAE = mean absolute error

SC = similarity coefficient

r² = correlation coefficient

q² = leave one out correlation coefficient

Reference 5

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

Scientifically accepted calculation method. The substance is entirely within the applicability domain (AD) of the submodel according to Meylan et al. (1997/1999), but the calculation methods according to Arnot & Gobas (2003) and Arnot et al. (2008) may be less accurate, due to the substance's property to appreciably ionize at physiological pH.

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) for the uncharged molecule at 25 °C as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

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:

Metabolite # 85 of the parent compound IPDA (CAS 2855-13-2)
- CAS Numbers: 99799-03-8, 60065-24-9, 60065-21-6 (no single CAS# identified, due to stereochemistry)
- SMILES: CC(=CC(C)(C)C)C(O)=O
- determined with the estimation model CATALOGIC 301C v09.13 (OASIS Catalogic v5.11.19)

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01 (EPI Suite v4.11)
- Result based on calculated log Pow of: 2.76 (KOWWIN v1.68, EPI Suite v4.11)

Type:

BCF

Value:

3.16 L/kg

Basis:

not specified

Remarks on result:

other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).

Type:

BCF

Value:

55.59 L/kg

Basis:

not specified

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Type:

BCF

Value:

62.82 L/kg

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

55.6 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

68.17 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Details on kinetic parameters:

Biotransformation half-life (days): 1.285
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): 0.540 / day
The substance is not within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b), as the substance appreciably ionizes at physiologically relevant pH.

Summary Results:

Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)

Biotransformation Half-Life (days) : 1.28 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 1.75 (BAF = 55.6 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 2.76

 

Equation Used to Make BCF estimate:

Log BCF = 0.50 (Ionic; Log Kow dependent)

 

Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

TYPE	NUM	LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	1	Aliphatic acid  [-C(=O)-OH]	0.3803	0.3803
Frag	1	Carbon with 4 single bonds & no hydrogens	-0.2984	-0.2984
Frag	4	Methyl [-CH3]	0.2451	0.9804
Frag	1	-C=CH [alkenyl hydrogen]	0.0988	0.0988
Frag	1	-C=CH [alkenyl hydrogen]	0.0000	0.0000
L Kow	*	Log Kow =  2.76 (KowWin estimate)	0.3073	0.8493
MolWt	*	Molecular Weight Parameter		-0.3646
Const	*	Equation Constant		-1.5371
RESULT	LOG Bio Half-Life (days)			0.1088
RESULT	Bio Half-Life (days)			1.285
NOTE	Bio Half-Life Normalized to 10 g fish at 15 deg C

 

Biotransformation Rate Constant:

kM (Rate Constant): 0.5396 /day (10 gram fish)

kM (Rate Constant): 0.3034 /day (100 gram fish)

kM (Rate Constant): 0.1706 /day (1 kg fish)

kM (Rate Constant): 0.09595 /day (10 kg fish)

 

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

Estimated Log BCF (upper trophic) = 1.745 (BCF = 55.59 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 1.745 (BAF = 55.6 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 1.583 (BCF = 38.33 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 1.584 (BAF = 38.35 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 1.531 (BCF = 33.99 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 1.532 (BAF = 34.06 L/kg wet-wt)

 

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

Estimated Log BCF (upper trophic) = 1.798 (BCF = 62.82 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 1.834 (BAF = 68.17 L/kg wet-wt)

Reference 6

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

Scientifically accepted calculation method. The substance is entirely within the applicability domain (AD) of the submodel according to Meylan et al. (1997/1999), but the calculation methods according to Arnot & Gobas (2003) and Arnot et al. (2008) may be less accurate, due to the substance's property to appreciably ionize at physiological pH. According to the submodel Arnot et al. (2008), the substance is not within the applicability domain of the submodel, as the maximum number of instances of biotransformation fragments is exceeded.

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) for the uncharged molecule at 25 °C as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

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:

Metabolite # 73 of the parent compound IPDA (CAS 2855-13-2)
- CAS Number: 3302-09-8
- SMILES: CC(CC(C)(C)C)C(O)=O
- determined with the estimation model CATALOGIC 301C v09.13 (OASIS Catalogic v5.11.19)

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01 (EPI Suite v4.11)
- Result based on calculated log Pow of: 2.85 (KOWWIN v1.68, EPI Suite v4.11)

Type:

BCF

Value:

3.16 L/kg

Basis:

not specified

Remarks on result:

other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).

Type:

BCF

Value:

59.98 L/kg

Basis:

not specified

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Type:

BCF

Value:

76.22 L/kg

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

59.98 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

83.94 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Details on kinetic parameters:

Biotransformation half-life (days): 0.731
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): 0.948 / day
The substance is not within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b), as the substance appreciably ionizes at physiologically relevant pH. In addition, the maximum number of instances of biotransformation fragments is exceeded.

Summary Results:

Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)

Biotransformation Half-Life (days) : 0.731 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 1.78 (BAF = 60 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 2.85

 

Equation Used to Make BCF estimate:

Log BCF = 0.50 (Ionic; Log Kow dependent)

 

 

Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

TYPE	NUM	LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	1	Aliphatic acid  [-C(=O)-OH]	0.3803	0.3803
Frag	1	Carbon with 4 single bonds & no hydrogens	-0.2984	-0.2984
Frag	4	Methyl [-CH3]	0.2451	0.9804
Frag	1	-CH2- [linear]	0.0242	0.0242
Frag	1	-CH-  [linear]	-0.1912	-0.1912
L Kow	*	Log Kow =  2.85 (KowWin estimate)	0.3073	0.8756
MolWt	*	Molecular Weight Parameter		-0.3698
Const	*	Equation Constant		-1.5371
RESULT	LOG Bio Half-Life (days)			-0.1361
RESULT	Bio Half-Life (days)			0.731
NOTE	Bio Half-Life Normalized to 10 g fish at 15 deg C

 

Biotransformation Rate Constant:

kM (Rate Constant): 0.9482 /day (10 gram fish)

kM (Rate Constant): 0.5332 /day (100 gram fish)

kM (Rate Constant): 0.2999 /day (1 kg fish)

kM (Rate Constant): 0.1686 /day (10 kg fish)

 

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

Estimated Log BCF (upper trophic) = 1.778 (BCF = 59.98 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 1.778 (BAF = 59.98 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 1.641 (BCF = 43.74 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 1.641 (BAF = 43.76 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 1.594 (BCF = 39.23 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 1.594 (BAF = 39.31 L/kg wet-wt)

 

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

Estimated Log BCF (upper trophic) = 1.882 (BCF = 76.22 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 1.924 (BAF = 83.94 L/kg wet-wt)

Reference 7

Endpoint:

bioaccumulation in aquatic species: fish

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

2016

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

Remarks:

According to the model’s global AD index, the predicted substance is not within the applicability domain of the model.

Justification for type of information:

1. SOFTWARE
VEGA platform v1.1.3

2. MODEL (incl. version number)
BCF model (Meylan) v1.0.3

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

The BCF is estimated based on log Kow. The applicability domain of predictions is assessed using an Applicability Domain Index (ADI) calculated by grouping several other indices, e.g. by a similarity index that consider molecule's fingerprint and structural aspects (count of atoms, rings and relevant fragments).

GLP compliance:

no

Specific details on test material used for the study:

- SMILES code: NCC(CC(N)CC1(C)C)(C1)C

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: VEGA Meylan v1.0.3 implemented in the VEGA tool v.1.1.3 (calculation core v1.2.2)
- Result based on calculated log Pow of: 1.9 (calculated by VEGA: Meylan/KOWWIN)

Key result

Type:

BCF

Value:

8 L/kg

Remarks on result:

other: According to the model’s global AD index, the predicted substance is not within the applicability domain of the model. An expert analysis can be found in chapter "Administrative Data, Attached justification".

Type:

other: log BCF

Value:

0.92 other: log(L/kg)

Remarks on result:

other: According to the model’s global AD index, the predicted substance is not within the applicability domain of the model. An expert analysis can be found in chapter "Administrative Data, Attached justification".

Reference 8

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

Scientifically accepted calculation method. The substance is entirely within the applicability domain (AD) of the submodel according to Meylan et al. (1997/1999), but the calculation methods according to Arnot & Gobas (2003) and Arnot et al. (2008) may be less accurate, due to the substance's property to appreciably ionize at physiological pH.

Justification for type of information:

1. SOFTWARE
Estimation Programs Interface (EPI) Suite for Microsoft Windows, v4.11 (US EPA, 2012)

2. MODEL (incl. version number)
BCFBAF v3.01

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the bioconcentration factor (BCF) for the uncharged molecule at 25 °C as required information point under Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species, preferably fish (see also attached QMRF).
- See attached QPRF for reliability assessment.

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:

Metabolite # 105 of the parent compound IPDA (CAS 2855-13-2)
- CAS Numbers: 1118-47-4
- SMILES: CC(C)(C)CCC(O)=O
- determined with the estimation model CATALOGIC 301C v09.13 (OASIS Catalogic v5.11.19)

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS INFORMATION
- Measured/calculated logPow: calculated

BASIS FOR CALCULATION OF BCF
- Estimation software: BCFBAF v3.01 (EPI Suite v4.11)
- Result based on calculated log Pow of: 2.43 (KOWWIN v1.68, EPI Suite v4.11)

Type:

BCF

Value:

3.16 L/kg

Basis:

not specified

Remarks on result:

other: The substance is within the applicability domain of the BCFBAF submodel: Bioconcentration factor (BCF; Meylan et al., 1997/1999).

Type:

BCF

Value:

25.6 L/kg

Basis:

not specified

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF Arnot & Gobas, 2003).

Type:

BCF

Value:

29.74 L/kg

Calculation basis:

steady state

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

25.6 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation estimates; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Type:

BAF

Value:

31.09 L/kg

Basis:

not specified

Remarks on result:

other: Upper trophic, incl. biotransformation rate of zero; The substance is not within the applicability domain of the BCFBAF submodel: Arnot & Gobas BAF and steady-state BCF (Arnot & Gobas, 2003).

Details on kinetic parameters:

Biotransformation half-life (days): 0.552
Biotransformation rate (kM, normalised to 10 g fish at 15 °C): 1.256 / day
The substance is not within the applicability domain of the BCFBAF submodel: Biotransformation rate in fish (kM; Arnot et al., 2008a/b), as the substance appreciably ionizes at physiologically relevant pH.

Summary Results:

Log BCF (regression-based estimate): 0.50 (BCF = 3.16 L/kg wet-wt)

Biotransformation Half-Life (days) : 0.552 (normalized to 10 g fish)

Log BAF (Arnot-Gobas upper trophic): 1.41 (BAF = 25.6 L/kg wet-wt)

 

Log Kow (experimental): not available from database

Log Kow used by BCF estimates: 2.43

 

Equation Used to Make BCF estimate:

Log BCF = 0.50 (Ionic; Log Kow dependent)

 

Estimated Log BCF = 0.500 (BCF = 3.162 L/kg wet-wt)

 

Whole Body Primary Biotransformation Rate Estimate for Fish:

TYPE	NUM	LOG BIOTRANSFORMATION FRAGMENT DESCRIPTION	COEFF	VALUE
Frag	1	Aliphatic acid  [-C(=O)-OH]	0.3803	0.3803
Frag	1	Carbon with 4 single bonds & no hydrogens	-0.2984	-0.2984
Frag	3	Methyl [-CH3]	0.2451	0.7353
Frag	2	-CH2- [linear]	0.0242	0.0484
L Kow	*	Log Kow =  2.43 (KowWin estimate)	0.3073	0.7472
MolWt	*	Molecular Weight Parameter		-0.3338
Const	*	Equation Constant		-1.5371
RESULT	LOG Bio Half-Life (days)			-0.2581
RESULT	Bio Half-Life (days)			0.5519
NOTE	Bio Half-Life Normalized to 10 g fish at 15 deg C

 

Biotransformation Rate Constant:

kM (Rate Constant): 1.256 /day (10 gram fish)

kM (Rate Constant): 0.7063 /day (100 gram fish)

kM (Rate Constant): 0.3972 /day (1 kg fish)

kM (Rate Constant): 0.2233 /day (10 kg fish)

 

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

Estimated Log BCF (upper trophic) = 1.408 (BCF = 25.6 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 1.408 (BAF = 25.6 L/kg wet-wt)

Estimated Log BCF (mid trophic)  = 1.257 (BCF = 18.07 L/kg wet-wt)

Estimated Log BAF (mid trophic)  = 1.257 (BAF = 18.07 L/kg wet-wt)

Estimated Log BCF (lower trophic) = 1.208 (BCF = 16.13 L/kg wet-wt)

Estimated Log BAF (lower trophic) = 1.208 (BAF = 16.15 L/kg wet-wt)

 

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

Estimated Log BCF (upper trophic) = 1.473 (BCF = 29.74 L/kg wet-wt)

Estimated Log BAF (upper trophic) = 1.493 (BAF = 31.09 L/kg wet-wt)

Reference 9

Endpoint:

bioaccumulation: aquatic / sediment

Type of information:

(Q)SAR

Adequacy of study:

other information

Study period:

2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Accepted calculation method

Justification for type of information:

QSAR prediction: migrated from IUCLID 5.6

Principles of method if other than guideline:

calculation with BCFWin v2.14 as integrated in EPIWIN v3.10, Syracuse Research Center / U.S. EPA

Test organisms (species):

other: QSAR estimate

Details on estimation of bioconcentration:

log Kow used: 0.99

Type:

BCF

Value:

3.16

Validity criteria fulfilled:

not applicable

Conclusions:

The bioconcentration factor of isophorone diamine was calculated to be 3.16 with the BCFWin v2.14 software. This corresponds to a low bioaccumulation potential.

Executive summary:

The bioconcentration factor of isophorone diamine was calculated to be 3.16 with the BCFWin v2.14 software. This corresponds to a low bioaccumulation potential.

Reference 10

Endpoint:

bioaccumulation in aquatic species: fish

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

Remarks:

The substance is not within the applicability domain of the model due to 25% of fragments not present in the training set

Justification for type of information:

1. SOFTWARE
OASIS Catalogic v5.11.19

2. MODEL (incl. version number)
BCF base-line model v02.09 - July 2015

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See section 'Test Material'.

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See attached QMRF.

5. APPLICABILITY DOMAIN
See attached QPRF.

6. ADEQUACY OF THE RESULT
- The model is scientifically valid (see attached QMRF).
- The model estimates the Bioconcentration factor (BCF) as required information point according to Regulation (EC) No 1907/2006 [REACH], Annex IX, 9.3.2 Bioaccumulation in aquatic species (preferably fish);
further related predictions: Apparent effect of mitigating factors / Maximum bioconcentration factor (BCFmax) / Maximum diameter of energetically stable conformers / Whole body primary biotransformation half-life / Metabolic biotransformation rate constant Km / Metabolites and their quantitative distribution
- See attached QPRF for reliability assessment.

Principles of method if other than guideline:

Calculation using Catalogic v.5.11.19, BCF base-line model v.02.09

GLP compliance:

no

Test organisms (species):

other: fish

Details on estimation of bioconcentration:

BASIS FOR CALCULATION OF BCF
- Estimation software: OASIS Catalogic v5.11.19 [BCF base line model - v.02.09]

Key result

Type:

BCF

Value:

6.92 L/kg

Remarks on result:

other: considering all mitigating factors; the substance is not within the applicability domain of the model.

Key result

Type:

BCF

Value:

14.6 L/kg

Remarks on result:

other: without considering any mitigating factors; the substance is not within the applicability domain of the model.

Metabolites:

The model Catalogic 301 C v09.13 (OASIS Catalogic v5.11.19) calculated 112 metabolites (see document "2855-13-2_Metabolite prediction_Catalogic 301C v09.13_2017-01-25" attached under "attached background material") identifying 40 metabolites as relevant degradation products, with an estimated quantity of ≥ 0.1%.
Three relevant metabolites were predicted by the model to exhibit a higher log Kow than the parent compound Isophorone diamine itself (Table 2, see "Any other information on results incl. tables").

DOMAIN APPLICABILITY

With regard to the parametric and the mechanistic domain, the test substance is 100% within the applicability domain of the model, whereas it is out of the applicability domain of the structural domain (25% unknown fragments).

MOLECULE SIZE (Maximum diameter)

Minimum: 9.095 Å

Maximum: 10.321 Å

Mean: 9.669 Å

Table 1: EFFECTS OF MITIGATING FACTORS

Mitigation factor	Predicted value		Magnitude of effect*
	BCF	log BCF	(as log BCF)
Without mitigation	14.6	1.165 ± 0.0	-
Combination of all factors	6.92	0.84 ± 0.0594	0.325
Acids			0.000
Metabolism			0.000
Phenols			0.000
Molecular size			0.0972
Water Solubility			0.815

* The magnitude of the effect on the BCF by the single mitigating factors should be regarded as tentative information as the factors influence each other. The effect of individual mitigating factors (e.g. metabolism) is calculated as:

Mitigating effect of metabolism = log BCF_corrected(all factors except for metabolism) – log BCF_corrected(all factors)

RESULTS AND DISCUSSION

The BCF base-line model estimates the BCF to be 6.92 taking all mitigating factors into consideration. The maximum BCF was calculated to be 14.6. Mitigating factors like molecular size and the water solubility were considered by the model. Water solubility had the highest mitigating effect on the bioaccumulation potential.

According to the OECD 305 technical guidance document, the degree of transformation of the parent is decisive for the effect of metabolism (i.e. the reproduction of subsequent steps is less critical for the prediction of the BCF).

Water solubility and molecular size reduce the log BCF as estimated by the model. Molecular size and water solubility are discussed within the literature whether certain threshold values are suitable as cut-off criteria for indication of limited bioaccumulation. Regarding molecular size, the PBT working group on hazardous substances discussed a maximum diameter of > 17.4 Å (Comber et al., 2006).

However, the average as well as the maximum diameter do not exceed this critical value.

CONCLUSIONS

- water solubility and to a minor extent molecular size reduce the bioaccumulation potential.

- The substance is not expected to exhibit a significant bioaccumulation potential.

- With regard to the structural domain, the test substance is not within the applicability domain of the model (25% unknown fragments).

Table 2: Log Kow values of the modelled relevant metabolites (predicted with Catalogic 301C v09.13 (OASIS Catalogic v5.11.19))

Metabolite	Quantity (%)	Log Kow
#73: SMILES: CC(CC(C)(C)C)C(O)=O 2,4,4-trimethylpentanoic acid: CAS# 3302-09-8	1.1	2.85
#85: SMILES: CC(=CC(C)(C)C)C(O)=O No single CAS-# identified, due to stereochemistry: A) 2-Pentenoic acid, 2,4,4-trimethyl-: CAS# 99799-03-8 B) 2-Pentenoic acid, 2,4,4-trimethyl-, (Z)- (9CI): CAS# 60065-24-9 C) 2-Pentenoic acid, 2,4,4-trimethyl-,(2E)-: CAS# 60065-21-6	0.9	2.76
#105: SMILES: CC(C)(C)CCC(O)=O Carboxylic acid, C6-8-neo: CAS-# 95823-36-2	0.9	2.43

Reference 11

Endpoint:

bioaccumulation in aquatic species: fish

Data waiving:

other justification

Justification for data waiving:

other:

Description of key information

Significant accumulation in organisms is not to be expected.

Additional information

 QSAR-disclaimer In Article 13 of Regulation (EC) No 1907/2006, it is laid down that information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI (of the same Regulation) are met. Furthermore, according to Article 25 of the same Regulation testing on vertebrate animals shall be undertaken only as a last resort. According to Annex XI of Regulation (EC) No 1907/2006 (Q)SAR results can be used if (1) the scientific validity of the (Q)SAR model has been established, (2) the substance falls within the applicability domain of the (Q)SAR model, (3) the results are adequate for the purpose of classification and labelling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided. For the assessment of Isophorone diamine (CAS 2855-13-2)(Q)SAR results were used for bioaccumulation. The criteria listed in Annex XI of Regulation (EC) No 1907/2006 are considered to be adequately fulfilled and therefore the endpoint(s) sufficiently covered and suitable for risk assessment. Therefore, and for reasons of animal welfare, further experimental studies on bioaccumulation are not provided. Assessment of the parent compound: In accordance with column 2 of REACH Annex IX, the study does not need to be conducted since the substance has a log Kow less or equal than 3. Isophorone diamine has a measured log Kow of 0.99 (Hüls Infracor GmbH 1998) However, in order to assess the bioaccumulation potential of the test substance, the BCF was calculated with several estimation models. The table below lists the applied (Q)SAR models, the estimated BCF values and basic information on the applicability domain (AD). Detailed information on the model’s results and the AD are given in the endpoint study records of IUCLID Chapter 5.3.1. The selected models comply with the OECD principles for (Q)SAR models. Summary of relevant information on aquatic bioaccumulation: Predicted BCF values for applied QSAR models sorted by BCF (AD = Applicability Domain) ModelBCFIn ADRemarks / RestraintsBCFBAF v3.01 (EPI Suite v4.11):Arnot-Gobas BCF, upper trophic, incl. biotransformation1.9no- the substance does appreciably ionize at physiological pH.- maximum number of instances of biotransformation fragments in a training set compound was exceeded BCFBAF v3.01 (EPI Suite v4.11):Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero1.9no- the substance does appreciably ionize at physiological pH. KNN/Read Across v1.1.0(VEGA v1.1.3)2.6no- accuracy of prediction for similar molecules not optimal- the maximum error in prediction of similar molecules has a moderate value CAESAR v2.1.14 (VEGA v1.1.3)3no- only moderately similar compounds have been found- accuracy of prediction for similar molecules not optimal- the maximum error in prediction of similar molecules high value BCFBAF v3.01 (EPI Suite v4.11):Meylan et al. 1997/19993.2yes---BCF baseline model v02.09(OASIS Catalogic v5.11.19): incl. mitigating factors6.9no25% of fragments not present in the training set Meylan v1.0.3 (VEGA v1.1.3)8no- only moderately similar compounds have been found- accuracy of prediction for similar molecules not optimal- the maximum error in prediction of similar molecules high value- reliability of logP value used by the model is not adequate T.E.S.T. v4.2.1:Consensus method9.3yes---BCF baseline model v02.09(OASIS Catalogic v5.11.17): not considering mitigating factors14.6no25% of fragments not present in the training set. Considering all of the applied (Q)SAR models, the calculated BCF values range from 1.9 to 14.6 L/kg, indicating a low potential for bioaccumulation. In addition, IPDA has a measured log Kow of 0.99(Hüls Infracor GmbH 1998), which is clearly<= 3.Assessment of relevant metabolites The model Catalogic 301 C v09.13 (OASIS Catalogic v5.11.19) calculated 112 metabolites of IPDA, identifying 40 metabolites as relevant degradation products, with an estimated quantity of >= 0.1%(for details see ‘Attached background material’ of the respective Endpoint Study Record in IUCLID chapter 5.2.1).Overall, the 112 modelled degradation products of IPDA were estimated to exhibit log Kow values in a range of -4.39 to 2.85, which is<=3. However, three relevant metabolites were predicted by the model to exhibit a higher log Kow than the parent compound itself (log Kow of the metabolites between 2.43 and 2.85). Therefore, the BCF of those metabolites was estimated with the model BCFBAF v3.01 (EPI Suite v4.11). The estimated BCF values are summarized in the table below: Summary of relevant information on aquatic bioaccumulation: Predicted BCF values of the metabolites for applied QSAR models (AD = Applicability Domain)ModelBCFIn ADRestraintsMetabolite #73BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)3.16yes-BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation59.98no- the substance ionizes at physiologically relevant pH BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero76.22no- the substance ionizes at physiologically relevant pHMetabolite #85BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)3.16yes-BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation55.59no- the substance ionizes at physiologically relevant pH BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero62.82no- the substance ionizes at physiologically relevant pH Metabolite #105BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)3.16yes-BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation25.6no- the substance ionizes at physiologically relevant pH BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero29.74no- the substance ionizes at physiologically relevant pH Considering all of the applied (Q)SAR models, the calculated BCF values of the relevant metabolites range from 3.2 to 76.2 L/kg, indicating a low potential for bioaccumulation. ConclusionBased on the available information on the log Kow of the parent compound and the relevant metabolites and supported by a weight -of-evidence approach from calculated data, it can be concluded that significant accumulation in organisms is not to be expected.