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Environmental fate & pathways

Bioaccumulation: aquatic / sediment

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Description of key information

Significant accumulation in organisms is not to be expected.

Key value for chemical safety assessment

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 labeling and/or risk assessment and (4) adequate and reliable documentation of the applied method is provided.

For the assessment of modified Isophoronediamine (CAS 93940 -97 -7) (Q)SAR results were used for aquatic 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 aquatic bioaccumulation are not provided.

 

Assessment:

In accordance with column 2 of REACH Annex IX, the study need not be conducted since the substance has a log Kow ≤ 3. The substance modified Isophoronediamine (MIPDA, CAS 93940 -97 -7) has a measured log Kow of 2.0 (@ pH 6, 23°C, BASF SE 2017, report no. 17L00094).  

 

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 (AD = Applicability Domain)

Model

BCF [L/kg]

In AD

Restraints

CAESAR v2.1.14 (VEGA v1.1.3)

3

no

- no similar compounds with known experimental value have been found

- accuracy of prediction for similar molecules is not optimal

- similar molecules have experimental values that disagree with predicted value

- the maximum error in prediction of similar molecules has a moderate value considering experimental variability

BCF baseline model v.02.09 (OASIS Catalogic v5.11.19): incl. mitigating factors

3

no

With regard to the structural domain, the test substance is not within the applicability domain of the model (20% of fragments not present in training set chemicals).

Meylan v1.0.3 (VEGA v1.1.3)

8

no

- only moderately similar compounds with known experimental value have been found

- similar molecules have experimental values that disagree with the predicted value

-the maximum error in prediction of similar molecules has a moderate value, considering the experimental variability

- reliability of logP value is not optimal

BCF KNN/Read-Across v1.1.0 (VEGA v1.1.3)

9.33

no

- only moderately similar compounds with known experimental value have been found

- accuracy of prediction for similar molecules is not optimal

- some similar molecules have experimental

values that disagree with the predicted value 

- the maximum error in prediction of similar molecules has a high value, considering the experimental variability

BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)

9.70

yes

-

BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation

11.1

no

- the substance ionizes at physiologically relevant pH

- the number of occurrences of one fragment exceeded those of the training set data

BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero

11.6

no

- the substance ionizes at physiologically relevant pH

- the number of occurrences of one fragment exceeded those of the training set data

US EPA T.E.S.T. v4.2.1: Bioaccumulation: Consensus method

35.5

yes

Based on the mean absolute errors of the models the confidence in the predicted results is low

BCF baseline model v.02.09 (OASIS Catalogic v5.11.19): not considering mitigating factors

40.2

no

With regard to the structural domain, the test substance is not within the applicability domain of the model (20% of fragments not present in training set chemicals).

Assessment of relevant metabolites:

CATALOGIC 301C v11.15 (OASIS Catalogic v5.13.1) was used to predicted the ready biodegradability of the substance as well as to predict potential metabolites. The substance was not completely within the applicability domain (100% parametric domain, 95% structural domain; 100% metabolic domain). The model predicted 129 metabolites, identifying 50 metabolites as relevant degradation products in terms of PBT/vPvB assessment, with an estimated quantity of ≥ 0.1% (equivalent to ≥ 0.001 mol/mol parent; for details see ‘Attached background material’ of the respective Endpoint Study Record). All metabolites have a log Kow ≤ 3. The log Kow of the relevant metabolites ranges from -4.19 to 2.86. In conclusion, all (relevant) predicted metabolites are not expected to significantly accumulate.

#

Meta-

bolite

(no)

Smiles

Quantity

(mol/mol

parent)

Log Kow

BOD

prediction

(% after

28 d)

parent

1

CC1(C)CC(NCCC#N)CC(C)(CNCCC#N)C1

1.16E-01

1.86

23

1

23

N#CCC=O

1.31E-02

-1.01

70

2

26

NCCC#N

2.45E-01

-1.13

47

3

3

CC1(C)CC(=O)CC(C)(CNCCC#N)C1

6.91E-04

1.38

24

4

2

CC1(C)CC(N)CC(C)(CNCCC#N)C1

1.46E-01

1.88

16

5

37

CC1(CO)CC(NCCC#N)CC(C)(CNCCC#N)C1

4.52E-07

0.40

30

6

55

CC1(C)CC(NCCC#N)CC(CNCCC#N)(CO)C1

2.26E-07

0.40

30

7

76

CC1(C)CC(NCCC#N)CC(C)(CNCCC(O)=O)C1

3.08E-03

-1.11

23

8

82

CC1(C)CC(NCCC(O)=O)CC(C)(CNCCC#N)C1

3.08E-03

-1.11

25

9

87

CC1(C)CC(NCCC#N)CC(C)(CNCCC(N)=O)C1

2.02E-03

0.84

22

10

88

CC1(C)CC(NCCC(N)=O)CC(C)(CNCCC#N)C1

2.02E-03

0.84

23

11

89

CC1(C)CC(NCCC#N)CC(C)(C(O)NCCC#N)C1

3.89E-04

0.32

23

12

94

CC1(C)CC(NCCC#N)CC(C)(CNC(O)CC#N)C1

2.76E-06

0.32

32

13

100

CC1(C)CC(C)(CNCCC#N)CC(O)(NCCC#N)C1

1.04E-03

1.06

20

14

102

CC1(C)CC(NC(O)CC#N)CC(C)(CNCCC#N)C1

2.76E-06

0.32

26

15

103

CC1(C)CC(NCCC#N)OC(=O)C(C)(CNCCC#N)C1

3.06E-04

1.11

29

16

106

CC1(C)CC(C)(CNCCC#N)CC(NCCC#N)OC1=O

3.06E-04

1.11

28

17

109

CC1(C)CC(NCCC#N)CC(C)(CNCCC#N)C(=O)O1

3.06E-04

-0.64

47

18

115

CC1(C)CC(C)(CNCCC#N)CC(NCCC#N)C(=O)O1

3.89E-04

-0.64

26

19

122

CC1(C)CC(NCCC#N)C(=O)OC(C)(CNCCC#N)C1

3.89E-04

-0.64

26

20

128

CC1(C)CC(NCCC#N)CC(C)(CNCCC#N)OC1=O

3.06E-04

-0.64

35

21

24

N#CCC(O)=O

3.60E-01

-0.76

65

22

4

CC1(C)CC(=O)OCC(C)(CNCCC#N)C1

3.82E-02

0.93

23

23

27

CC1(C)CC(C)(CNCCC#N)CC(=O)OC1

3.82E-02

0.93

20

24

38

CC1(C=O)CC(NCCC#N)CC(C)(CNCCC#N)C1

4.52E-07

0.37

30

25

56

CC1(C)CC(NCCC#N)CC(CNCCC#N)(C=O)C1

2.26E-07

0.37

30

26

77

CCNCC1(C)CC(NCCC#N)CC(C)(C)C1

9.19E-04

2.84

25

27

83

CCNC1CC(C)(C)CC(C)(CNCCC#N)C1

9.19E-04

2.84

25

28

91

CC1(C)CC(=O)CC(C)(C(O)NCCC#N)C1

7.41E-04

-0.16

22

29

90

CC1(C)CC(N)CC(C)(C(O)NCCC#N)C1

4.45E-04

0.34

15

30

95

CC1(C)CC(NCCC#N)CC(C)(CN)C1

3.88E-04

1.88

24

31

101

CC1(C)CC(C)(CNCCC#N)CC(N)(O)C1

1.72E-08

1.08

24

32

104

CC(C)(CC(O)NCCC#N)CC(C)(CNCCC#N)C(O)=O

2.45E-06

-3.93

31

33

107

CC(C)(CC(C)(CC(O)NCCC#N)CNCCC#N)C(O)=O

2.45E-06

-3.93

27

34

110

CC(C)(O)CC(CC(C)(CNCCC#N)C(O)=O)NCCC#N

4.86E-05

-3.93

43

35

117

CC1(C)CC(C)(CNCCC#N)CC(=O)C(=O)O1

8.72E-04

0.91

24

36

116

CC1(C)CC(C)(CNCCC#N)CC(N)C(=O)O1

4.45E-04

-0.62

20

37

124

CC1(C)CC(=O)C(=O)OC(C)(CNCCC#N)C1

8.72E-04

0.91

22

38

123

CC1(C)CC(N)C(=O)OC(C)(CNCCC#N)C1

4.45E-04

-0.62

21

39

129

CC(C)(CC(CC(C)(O)CNCCC#N)NCCC#N)C(O)=O

4.86E-05

-3.93

33

40

25

OC(=O)CC(O)=O

1.56E-02

-1.25

100

41

5

CC(C)(CC(O)=O)CC(C)(CNCCC#N)CO

2.77E-06

-2.36

31

42

28

CC(C)(CC(C)(CC(O)=O)CNCCC#N)CO

2.77E-06

-2.36

20

43

39

CC1(C(O)=O)CC(NCCC#N)CC(C)(CNCCC#N)C1

6.37E-03

-2.58

28

44

57

CC1(C)CC(NCCC#N)CC(CNCCC#N)(C(O)=O)C1

3.18E-03

-2.58

28

45

79

CCNCC1(C)CC(=O)CC(C)(C)C1

6.91E-04

2.35

25

46

78

CCNCC1(C)CC(N)CC(C)(C)C1

1.05E-03

2.86

17

47

85

CC=O

6.91E-04

-0.17

100

48

84

CCN

1.05E-03

-0.15

63

49

92

CC1(C)CC(=O)OCC(C)(C(O)NCCC#N)C1

5.93E-04

-0.61

24

50

93

CC1(C)CC(C)(C(O)NCCC#N)CC(=O)OC1

5.93E-04

-0.61

16

51

97

CC1(C)CC(=O)CC(C)(CN)C1

7.40E-04

1.40

18

52

96

CC1(C)CC(N)CC(C)(CN)C1

4.44E-04

1.90

15

53

105

CC(C)(CC=O)CC(C)(CNCCC#N)C(O)=O

2.45E-08

-2.39

31

54

108

CC(C)(CC(C)(CC=O)CNCCC#N)C(O)=O

2.45E-08

-2.39

20

55

111

CC(C)(O)CC(N)CC(C)(CNCCC#N)C(O)=O

6.01E-04

-3.91

42

56

112

CC(C)(O)CC(=O)CC(C)(CNCCC#N)C(O)=O

6.01E-04

-4.41

49

57

113

CC(C)(O)CC(CC(C)(CN)C(O)=O)NCCC#N

6.01E-04

-3.91

40

58

114

CC(C)(O)CC(CC(C)(C=O)C(O)=O)NCCC#N

6.01E-04

-3.93

48

59

118

CC(C)(O)CC(C)(CC(=O)C(O)=O)CNCCC#N

1.05E-08

-0.98

25

60

125

CC(C)(CC(=O)C(O)=O)CC(C)(O)CNCCC#N

1.05E-08

-0.98

31

61

130

CC(C)(CC(N)CC(C)(O)CNCCC#N)C(O)=O

6.01E-04

-3.91

30

62

131

CC(C)(CC(=O)CC(C)(O)CNCCC#N)C(O)=O

6.01E-04

-4.41

32

63

132

CC(C)(CC(CC(C)(O)CN)NCCC#N)C(O)=O

6.01E-04

-3.91

28

64

133

CC(C)(CC(CC(C)(O)C=O)NCCC#N)C(O)=O

6.01E-04

-3.93

37

65

7

CC(C)(CC(O)=O)CC(C)(CNCCC#N)C(O)=O

8.95E-02

-2.72

29

66

6

CC(C)(CC(O)=O)CC(C)(CNCCC#N)C=O

2.77E-06

-2.39

31

67

30

CC(C)(CC(C)(CC(O)=O)CNCCC#N)C(O)=O

3.93E-02

-2.72

18

68

29

CC(C)(CC(C)(CC(O)=O)CNCCC#N)C=O

2.77E-06

-2.39

20

69

41

CC1(C(O)=O)CC(=O)CC(C)(CNCCC#N)C1

3.16E-12

-3.06

31

70

40

CC1(C(O)=O)CC(N)CC(C)(CNCCC#N)C1

7.29E-03

-2.56

21

71

59

CC1(C)CC(=O)CC(CNCCC#N)(C(O)=O)C1

1.58E-12

-3.06

31

72

58

CC1(C)CC(N)CC(CNCCC#N)(C(O)=O)C1

3.65E-03

-2.56

21

73

80

CCNCC1(C)CC(=O)OCC(C)(C)C1

1.93E-03

1.90

22

74

81

CCNCC1(C)CC(C)(C)CC(=O)OC1

1.93E-03

1.90

25

75

86

CC(O)=O

3.86E-08

0.09

100

76

98

CC1(C)CC(=O)OCC(C)(CN)C1

5.92E-04

0.95

17

77

99

CC1(C)CC(C)(CN)CC(=O)OC1

5.92E-04

0.95

13

78

119

CC(C)(O)CC(C)(CC(O)=O)CNCCC#N

1.48E-04

-2.85

22

79

126

CC(C)(CC(O)=O)CC(C)(O)CNCCC#N

3.38E-04

-2.85

28

80

8

CC(C)(C)CC(C)(CNCCC#N)C(O)=O

2.67E-02

-1.39

30

81

32

CC(C)(CC(C)(CC(O)=O)C=O)C(O)=O

6.60E-04

0.48

5

82

31

CC(C)(CC(C)(CC(O)=O)CN)C(O)=O

4.50E-02

-2.70

6

83

42

CC1(C(O)=O)CC(=O)OCC(C)(CNCCC#N)C1

1.75E-03

-3.51

40

84

51

CC1(CNCCC#N)CC(=O)OCC(C)(C(O)=O)C1

1.75E-03

-3.51

20

85

60

CC1(C)CC(=O)OCC(CNCCC#N)(C(O)=O)C1

8.76E-04

-3.51

25

86

65

CC1(C)CC(CNCCC#N)(C(O)=O)CC(=O)OC1

8.76E-04

-3.51

34

87

120

CC(C)(O)CC(C)(CC(O)=O)CN

4.53E-04

-2.83

12

88

121

CC(C)(O)CC(C)(CC(O)=O)C=O

4.53E-04

0.35

8

89

127

CC(C)(C)CC(C)(O)CNCCC#N

7.16E-04

1.09

29

90

10

CC(C)(C)CC(C)(C=O)C(O)=O

7.16E-04

1.81

30

91

9

CC(C)(C)CC(C)(CN)C(O)=O

3.10E-02

-1.37

22

92

33

CC(C)(CC(C)(CC(O)=O)C(O)=O)C(O)=O

1.87E-01

0.73

0

93

43

CC(CC(O)=O)(CC(C)(CNCCC#N)CO)C(O)=O

1.40E-07

-4.19

44

94

52

CC(CC(O)=O)(CC(C)(CO)C(O)=O)CNCCC#N

1.98E-03

-4.19

19

95

61

CC(C)(CC(O)=O)CC(CNCCC#N)(CO)C(O)=O

2.25E-03

-4.19

35

96

66

CC(C)(CC(CC(O)=O)(CNCCC#N)C(O)=O)CO

7.02E-08

-4.19

37

97

34

CC(CC(O)=O)(CC(C)(CO)C(O)=O)C(O)=O

1.44E-02

-0.73

0

98

44

CC(CC(O)=O)(CC(C)(CNCCC#N)C=O)C(O)=O

1.40E-07

-4.21

44

99

54

CC(CC(O)=O)(CC(C)(CO)C(O)=O)C=O

1.45E-03

-0.98

5

100

53

CC(CC(O)=O)(CC(C)(CO)C(O)=O)CN

2.26E-03

-4.17

8

101

62

CC(C)(C)CC(CNCCC#N)(CO)C(O)=O

6.71E-04

-2.85

36

102

67

CC(C)(CC(CC(O)=O)(CNCCC#N)C(O)=O)C=O

7.02E-08

-4.21

37

103

11

CC(C)(C)CC(C)(C(O)=O)C(O)=O

1.31E-07

1.48

27

104

45

CC(CC(O)=O)(CC(C)(CNCCC#N)C(O)=O)C(O)=O

1.98E-03

-3.96

42

105

63

CC(C)(C)CC(CN)(CO)C(O)=O

1.26E-03

-2.83

32

106

64

CC(C)(C)CC(CO)(C=O)C(O)=O

1.58E-03

0.35

44

107

68

CC(C)(CC(CC(O)=O)(CNCCC#N)C(O)=O)C(O)=O

9.88E-04

-3.96

34

108

12

CC(CC(C)(C)C)C(O)=O

1.71E-02

2.85

20

109

35

CC(CC(O)=O)(CC(CO)(CO)C(O)=O)C(O)=O

5.61E-04

-1.79

0

110

36

CC(CC(CC(O)=O)(CO)C(O)=O)(CO)C(O)=O

5.61E-04

-1.49

0

111

47

CC(CC(O)=O)(CC(C)(C=O)C(O)=O)C(O)=O

1.45E-03

-0.76

54

112

46

CC(CC(O)=O)(CC(C)(CN)C(O)=O)C(O)=O

2.26E-03

-3.94

36

113

70

CC(C)(CC(CC(O)=O)(C=O)C(O)=O)C(O)=O

7.24E-04

-0.76

37

114

69

CC(C)(CC(CC(O)=O)(CN)C(O)=O)C(O)=O

1.13E-03

-3.94

25

115

74

CC(C)(C)CC(CO)(C(O)=O)C(O)=O

1.26E-09

0.01

42

116

13

CC(=CC(C)(C)C)C(O)=O

1.49E-02

2.76

29

117

48

CC(CC(O)=O)(CC(C)(C(O)=O)C(O)=O)C(O)=O

8.35E-12

-0.50

51

118

71

CC(C)(CC(CC(O)=O)(C(O)=O)C(O)=O)C(O)=O

4.17E-12

-0.50

34

119

75

CC(C)(C)CC(CO)C(O)=O

1.26E-03

1.38

40

120

14

CC(C(O)C(C)(C)C)C(O)=O

1.30E-02

1.31

27

121

49

CC(CC(C)(CC(O)=O)C(O)=O)C(O)=O

5.57E-03

0.28

34

122

50

CC(CC(O)=O)CC(C)(C(O)=O)C(O)=O

2.78E-03

0.28

62

123

72

CC(C)(CC(CC(O)=O)C(O)=O)C(O)=O

2.78E-03

0.28

29

124

73

CC(C)CC(CC(O)=O)(C(O)=O)C(O)=O

1.39E-03

0.28

56

125

15

CC(=C(O)C(C)(C)C)C(O)=O

8.61E-07

1.88

41

126

16

CC(C(=O)C(C)(C)C)C(O)=O

1.13E-02

0.80

41

127

17

CC(C)(C)C(O)=O

7.21E-02

1.45

0

128

19

CCC(O)=O

7.48E-07

0.58

100

129

18

CC(C)(CO)C(O)=O

2.76E-03

-0.02

0

 

Conclusion:

The applied estimation models predicted for MIPDA (CAS 93940 -97 -7) BCF values in a range between 3 L/kg (CAESAR v2.1.14 Bioaccumulation model (VEGA v1.1.3); substance not within AD; BCF-baseline model v02.09 (OASIS Catalogic v5.11.19), considering mitigating factors, substance not within AD) and 40.2 L/kg (BCF-baseline model v02.09 (OASIS Catalogic v5.11.19), without considering mitigating factors, substance not within AD).

Based on the available estimated data on the log Kow (log Kow = 2.0; @ pH 6, 23°C, BASF SE 2017, report no. 17L00094) and supported by a weight-of-evidence approach from calculated data, it can be concluded that significant accumulation of the parent and its predicted metabolites in organisms is not to be expected.