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PBT assessment

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PBT assessment: overall result

Reference
Name:
3-[[3-[[(2-cyanoethyl)amino]methyl]-3,5,5-trimethylcyclohexyl]amino]propiononitrile
Type of composition:
legal entity composition of the substance
State / form:
liquid
>= 95 - <= 100 % (w/w)
Reference substance:
Composition 1
Reference substance:
Composition 1
This impurity is considered relevant for the classification and labelling of the substance
PBT status:
the substance is not PBT / vPvB
Justification:

Parent compound:

The available evidence on degradation is not sufficient for an assessment based on the Annex XIII criteria for persistence (P and vP). As the substance is concluded to be not readily biodegradable (according to OECD criteria), it should be considered as potentially P/vP from a precautionary point of view until further data become available.

However, the substance is not B/vB based on a measured log Kow of 2.0 (BASF SE 2017, report no. 17L00094). In addition, several QSAR calculations (calculated BCF values range between 3.0 L/kg and 40.2 L/kg, BASF SE 2016, 2017) indicate no potential for bioaccumulation.

The substance is also not T since the lowest available chronic value is >> 0.01 mg/L and the substance holds no relevant classification.

 

PBT / vPvB – Assessment for modelled metabolites of MIPDA (CAS 93940-97-7):

ECHA Guidance on information requirements and chemical safety assessment (v3.0, June 2017), Chapter R.11.4.1 specifies that “Constituents, impurities and additives should normally be considered relevant for the PBT/vPvB assessment when they are present in concentration of ≥ 0.1% (w/w)” […] “Similar arguments apply to relevant transformation/degradation products”.

In order to identify the relevant degradation products of MIPDA as a standard information requirement according to Column 1, Section 9.2.3. of Annex IX to REACH and for purposes of an assessment of potential PBT/vPvB properties, the metabolites were modelled using CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156).

Overall, the model calculated 129 metabolites (Table 1) identifying 50 metabolites as relevant degradation products in terms of PBT/vPvB assessment, with an estimated quantity of ≥0.1% (equivalent to quantity setting in OASIS CATALOGIC: ≥ 0.001 [mol/mol parent]).

 

Table 1: QSAR prediction for CAS-#93940-97-7 (MIPDA) using CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156;metabolites with a quantity > 0.001 mol/mol parent after 28 d are highlighted by grey background and bold type; metabolite no: according to (Q)SAR model Catalogic v11.15 – July 2018 (OASIS CATALOGIC v5.13.156))

#

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

 

Persistence (“P/vP”):

In order to assess the biodegradation potential of the relevant degradation products, the (Q)SAR model CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156) was applied.    

Concerning the applicability domain (OECD Principle 3) MIPDA is completely in the parametric and the metabolic domain (100%), but only partly in the structural domain (95%; 5% fragments were not in the training set). However, the model was used to predict potential metabolites.

- The model predicts a BOD value of 23% for MIPDA, supporting the result of the experimental data that the substance is not readily biodegradable. 

- 45 of the 50 metabolites identified as relevant degradation products were calculated to be not readily biodegradable (threshold value: <60% BOD). Individual biodegradation of these metabolites was estimated to be in a range of 0% to 56% after 28 days (based on BOD).

- Five of the relevant metabolites were estimated to be readily biodegradable (threshold value: ≥60%), with individually calculated biodegradation values between 65% and 100% after 28 days (based on BOD).

In conclusion, 90% of the predicted metabolites present in concentration of ≥0.1% (equivalent to quantity setting in OASIS CATALOGIC: 0.001 [mol/mol parent]) are estimated to be not readily biodegradable while 10% of the relevant metabolites are predicted to be readily biodegradable.

The degradation products of MIPDA (CAS-# 93940-97-7) which are predicted to be not readily biodegradable should be considered as potentially P/vP from a precautionary point of view, until further data become available.

 

Bioaccumulation (“B/vB”):

Referring to uncharged molecules, the estimation model CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156) calculated for the parent compound MIPDA (CAS-# 93940-97-7) a log Kow of 1.86, which is in good agreement with the experimentally determined log Kow of 2.0. Both values indicate a low potential for bioaccumulation.

Without exception, all of the 129 modelled degradation products of MIPDA were estimated to exhibit log Kow values of clearly ≤4.5 (see Table 1), thereby not fulfilling the screening criteria for bioaccumulation (B/vB) as laid down in Section 3.1 of REACH Annex XIII.

Based on the estimation data available for the modelled metabolites, all (relevant) metabolites of MIPDA are concluded to be “not B” and “not vB”.

 

Toxicity (“T”):

As the predicted degradation products are not likely to fulfill both the P/vP and B/vB criteria, no information was collected on their toxicity properties.

 

Overall conclusion:

1.  Sufficient test data are available to assess the PBT/vPvB properties of MIPDA.

2.  Potentially relevant degradation products were modeled using (Q)SARmodel CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156):

2a. Based on modeled data relevant degradation products present in concentration of ≥ 0.1% (equivalent to quantity setting in OASIS CATALOGIC: ≥0.001 [mol/mol parent]) do neither fulfill the PBT criteria (not PBT) nor the vPvB criteria (not vPvB).

2b. However, 45 predicted relevant metabolites present in concentration of ≥0.1% (equivalent to quantity setting in OASIS CATALOGIC: ≥0.001 [mol/mol parent]) should be considered as potentially P/vP from a precautionary point of view.