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PBT assessment

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PBT assessment: overall result

Reference
Name:
4,4'-methylenebis(2-methylcyclohexanamine)
Type of composition:
legal entity composition of the substance
State / form:
liquid
Reference substance:
Composition 1
PBT status:
the substance is not PBT / vPvB
Justification:

Parent compound:

An evaluation of the inherent properties of 2,2’-dimethyl-4,4’-methylenebis(cyclohexylamine) (DMDC; CAS no. 6864-37-5) is performed against Annex XIII criteria. If insufficient data were available, the screening criteria as laid down in ECHA Guidance on information requirements and chemical safety assessment R.11: PBT Assessment (v3.0, 2017) were applied.

 

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 as well as to be hydrolytically stable, it should be considered potentially P/vP from a precautionary point of view until further data become available.

 

A measured log Kow of 2.3 and results from a bioaccumulation study according to OECD TG 305 C (BCF < 60 L/kg) indicate that the substance is neither B nor vB.

 

Regarding aquatic toxicity the substance is not T since the lowest available chronic value is > 0.01 mg/L (experimental chronic toxicity data are available for Daphnia and algae. The chronic values are greater than 0.01 mg/L). Furthermore, results of the available short-term studies for fish, Daphnia and algae indicate that the L(E)C50 values are greater than the screening criterion of 0.1 mg/L (the lowest acute value is 4.6 mg/L for Daphnia). However, the substance is self-classified as STOT-RE. Identified target organs are skeletal muscle and liver. Hence, the substance fulfills the T-criterion.

Based on available data, no final conclusion can be drawn on the P/vP properties. The substance fulfills the T-criterion, but since it is not B/vB it can be regarded as not PBT and not vPvB.

PBT / vPvB - Assessment for modelled metabolites of DMDC (CAS 6864 -37 -5):

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 DMDC 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 128 metabolites (Table 1) identifying 37 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-#6864 -37 -5 (DMDC) 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))

#

Metab.
No

Smiles

Name

Quantity
(mol/mol parent)

Log Kow

BOD pred. (% after 28 d)

PBT-Assessment:
ECHA (disseminated substances)

Parent

1

CC1CC(CC2CCC(N)C(C)C2)CCC1N

4,4'-Methylenebis(2-methylcyclohexanamine) (CAS 6864-37-5)

1.24E-01

2.30

39

not PBT/vPvB

1

2

CC1CC(CC2CCC(=O)C(C)C2)CCC1N

not identified

7.95E-06

3.60

56

not checked

2

3

CC1CC(CC2(O)CCC(=O)C(C)C2)CCC1N

not identified

7.95E-06

2.09

55

not checked

3

4

CC1CC(CC2(O)CCC(=O)OC(C)C2)CCC1N

not identified

8.82E-02

1.64

54

not identified

4

5

CC1CC(CC(O)(CCC(O)=O)CC(C)O)CCC1N

not identified

7.07E-06

-1.24

58

not checked

5

6

CC1CC(CC(O)(CC(C)O)C=CC(O)=O)CCC1N

not identified

7.07E-06

0.04

58

not checked

6

7

CC1CC(CC(O)(CC(C)O)C(O)CC(O)=O)CCC1N

not identified

7.07E-06

-2.78

57

not checked

7

8

CC1CC(CC(O)(CC(C)O)C(=O)CC(O)=O)CCC1N

not identified

7.07E-06

-2.37

57

not checked

8

9

CC1CC(CC(O)(CC(C)O)C(O)=O)CCC1N

not identified

2.17E-01

-1.91

50

not identified

9

10

CC1CC(CC(O)(CC(C)=O)C(O)=O)CCC1N

not identified

4.90E-06

-2.83

58

not checked

10

11

CC1CC(CC(O)(COC(C)=O)C(O)=O)CCC1N

not identified

5.44E-02

-2.22

56

not identified

11

12

CC1CC(CC(O)(CO)C(O)=O)CCC1N

not identified

4.35E-06

-1.62

52

not checked

12

13

CC1CC(CC(O)(C=O)C(O)=O)CCC1N

not identified

4.35E-06

-3.25

52

not checked

13

14

CC1CC(CC(O)(C(O)=O)C(O)=O)CCC1N

not identified

4.48E-02

-3.59

50

not identified

14

15

CC1CC(CC(=O)C(O)=O)CCC1N

not identified

3.91E-06

0.39

58

not checked

15

16

CC1CC(CC(O)=O)CCC1N

not identified

3.91E-06

-1.48

56

not checked

16

17

CC1CC(O)(CC(O)=O)CCC1N

not identified

1.25E-01

-2.98

54

not identified

17

18

CC1CC(=O)CCC1N

not identified

9.95E-02

0.00

49

not identified

18

19

CC1CC(=O)CCC1=O

not identified

1.66E-06

-0.51

77

not checked

19

20

CC1CC(=O)CCC(=O)O1

not identified

1.84E-02

0.85

76

not identified

20

21

CC=CC(=O)CCC(O)=O

not identified

1.47E-06

0.57

85

not checked

21

22

OC(=O)CCC(O)=O

Succinic acid (CAS 110-15-8)

1.52E-02

-0.75

90

not PBT/vPvB

22

23

CCC(O)=O

Propionic acid (CAS 79-09-4)

1.35E-06

0.58

100

not checked

23

26

CC=C

Propene (CAS 115-07-1)

1.47E-06

1.68

80

not checked

24

27

CC1CO1

Methyloxirane (CAS 75-56-9)

1.47E-06

0.37

77

not checked

25

28

CC(O)CO

1,2-Propanediol (CAS 57-55-6)

1.47E-06

-0.78

73

not checked

26

29

CC(O)C=O

not identified

1.47E-06

-1.21

73

not checked

27

30

CC(O)C(O)=O

D-lactic acid (CAS 10326-41-7)

4.73E-02

-0.65

68

not PBT/vPvB

28

31

CC=O

Acetaldehyd (CAS 75-07-0)

1.00E-06

-0.17

100

not checked

29

32

CC(O)=O

Acetic acid (CAS 64-19-7)

1.61E-05

0.09

100

not checked

30

34

CC1CC(CC2CCC(N)C(CO)C2)CCC1N

not identified

4.70E-07

2.64

48

not checked

31

35

CC1CC(CC2CCC(N)C(C=O)C2)CCC1N

not identified

4.70E-07

2.61

48

not checked

32

36

CC1CC(CC2CCC(N)C(C(O)=O)C2)CCC1N

not identified

6.61E-03

-0.34

46

not identified

33

37

CC1CC(CC2CCC(N)C(C(O)=O)C2)CCC1=O

not identified

2.02E-07

-0.84

57

not checked

34

38

CC1CC(O)(CC2CCC(N)C(C(O)=O)C2)CCC1=O

not identified

2.02E-07

-2.34

56

not checked

35

39

CC1CC(O)(CC2CCC(N)C(C(O)=O)C2)CCC(=O)O1

not identified

2.24E-03

-2.79

55

not identified

36

40

CC(O)CC(O)(CCC(O)=O)CC1CCC(N)C(C(O)=O)C1

not identified

1.79E-07

-3.06

62

not checked

37

41

CC(O)CC(O)(CC1CCC(N)C(C(O)=O)C1)C=CC(O)=O

not identified

1.79E-07

-3.28

62

not checked

38

42

CC(O)CC(O)(CC1CCC(N)C(C(O)=O)C1)C(O)CC(O)=O

not identified

1.79E-07

-4.60

61

not checked

39

43

CC(O)CC(O)(CC1CCC(N)C(C(O)=O)C1)C(=O)CC(O)=O

not identified

1.79E-07

-4.20

61

not checked

40

44

CC(O)CC(O)(CC1CCC(N)C(C(O)=O)C1)C(O)=O

not identified

5.51E-03

-3.74

55

not identified

41

45

CC(=O)CC(O)(CC1CCC(N)C(C(O)=O)C1)C(O)=O

not identified

1.24E-07

-4.65

60

not checked

42

46

CC(=O)OCC(O)(CC1CCC(N)C(C(O)=O)C1)C(O)=O

not identified

1.38E-03

-4.04

59

not identified

43

47

NC1CCC(CC(O)(CO)C(O)=O)CC1C(O)=O

not identified

1.11E-07

-3.44

57

not checked

44

48

NC1CCC(CC(O)(C=O)C(O)=O)CC1C(O)=O

not identified

1.11E-07

-5.08

57

not checked

45

49

NC1CCC(CC(O)(C(O)=O)C(O)=O)CC1C(O)=O

not identified

1.14E-03

-4.82

55

not identified

46

50

NC1CCC(CC(=O)C(O)=O)CC1C(O)=O

not identified

9.91E-08

-4.63

65

not checked

47

51

NC1CCC(CC(O)=O)CC1C(O)=O

not identified

9.91E-08

-3.30

64

not checked

48

52

NC1CCC(O)(CC(O)=O)CC1C(O)=O

not identified

3.18E-03

-4.81

62

not identified

49

53

NC1CCC(=O)CC1C(O)=O

not identified

2.53E-03

-4.44

45

not identified

50

54

OC(=O)C1CC(=O)CCC1=O

not identified

4.21E-13

-1.74

74

not checked

51

55

OC(=O)C1CC(=O)OCCC1=O

not identified

2.10E-03

-0.39

67

not identified

52

56

OC(=O)C1COC(=O)CCC1=O

not identified

2.10E-03

-0.39

78

not identified

53

57

CC1CC(CC2CCC(=O)C(C(O)=O)C2)CCC1N

not identified

2.64E-03

-0.84

62

not identified

54

58

CC1CC(CC(CCC(O)=O)CCC(O)=O)CCC1N

not identified

1.75E-12

-0.43

74

not checked

55

59

CC1CC(CC(CCC(O)=O)C=CC(O)=O)CCC1N

not identified

1.75E-07

-0.65

74

not checked

56

60

CC1CC(CC(CCC(O)=O)C(O)CC(O)=O)CCC1N

not identified

1.75E-07

-1.97

73

not checked

57

61

CC1CC(CC(CCC(O)=O)C(=O)CC(O)=O)CCC1N

not identified

1.75E-07

-2.48

73

not checked

58

62

CC1CC(CC(CCC(O)=O)C(O)=O)CCC1N

not identified

1.75E-07

-1.41

69

not checked

59

63

CC1CC(CC(C=CC(O)=O)C(O)=O)CCC1N

not identified

1.75E-07

-1.63

69

not checked

60

64

CC1CC(CC(C(O)CC(O)=O)C(O)=O)CCC1N

not identified

1.75E-07

-2.95

68

not checked

61

65

CC1CC(CC(C(=O)CC(O)=O)C(O)=O)CCC1N

not identified

1.75E-07

-3.46

68

not checked

62

66

CC1CC(CC(C(O)=O)C(O)=O)CCC1N

not identified

3.00E-04

-2.39

62

not checked

63

67

CC1CC(CCC(O)=O)CCC1N

not identified

1.72E-07

-0.99

59

not checked

64

68

CC1CC(C=CC(O)=O)CCC1N

not identified

1.72E-07

0.30

59

not checked

65

69

CC1CC(C(O)CC(O)=O)CCC1N

not identified

1.72E-07

-2.53

57

not checked

66

70

CC1CC(C(=O)CC(O)=O)CCC1N

not identified

1.72E-07

-3.04

57

not checked

67

71

CC1CC(C(O)=O)CCC1N

not identified

6.47E-03

-1.97

46

not identified

68

72

CC1CC(C(O)=O)CCC1=O

not identified

1.08E-07

0.72

77

not checked

69

73

CC1CC(O)(C(O)=O)CCC1=O

not identified

1.08E-07

-0.47

76

not checked

70

74

CC1CC(O)(C(O)=O)CCC(=O)O1

not identified

1.20E-03

-0.92

74

not identified

71

75

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

not identified

9.57E-08

-1.19

96

not checked

72

76

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

not identified

9.57E-08

-1.40

96

not checked

73

77

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

not identified

9.57E-08

-1.53

95

not checked

74

78

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

not identified

9.57E-08

-2.32

95

not checked

75

79

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

not identified

2.94E-03

-2.17

93

not identified

76

80

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

not identified

6.63E-03

-3.09

91

not identified

77

82

CC1CC(CC2CC(C)C(N)CC(=O)O2)CCC1N

not identified

6.36E-04

1.60

42

not checked

78

83

CC1CC(CC(O)CC(C)C(N)CC(O)=O)CCC1N

not identified

7.17E-04

-1.69

39

not checked

79

84

CC1CC(CC(O)CC(C)C(N)CC(O)=O)CCC1=O

not identified

2.19E-08

-2.19

56

not checked

80

85

CC(CC(O)CC1(O)CCC(=O)C(C)C1)C(N)CC(O)=O

not identified

2.19E-08

-3.29

55

not checked

81

86

CC(CC(O)CC1(O)CCC(=O)OC(C)C1)C(N)CC(O)=O

not identified

2.43E-04

-3.74

53

not checked

82

87

CC(CC(O)CC(O)(CCC(O)=O)CC(C)O)C(N)CC(O)=O

not identified

1.95E-03

-4.42

59

not identified

83

88

CC1CC(CC(O)CC(C)C(=O)CC(O)=O)CCC1N

not identified

2.19E-08

-2.19

48

not checked

84

89

CC1CC(CC(O)CC(C)C(O)=O)CCC1N

not identified

2.86E-04

-1.13

40

not checked

85

90

CC1CC(CC(O)C=C(C)C(O)=O)CCC1N

not identified

1.90E-03

0.29

44

not identified

86

91

CC1CC(CC2CCC(N)C(C)C(=O)O2)CCC1N

not identified

6.36E-04

1.60

33

not checked

87

92

CC1CC(CC(O)CCC(N)C(C)C(O)=O)CCC1N

not identified

6.66E-04

-1.69

34

not checked

88

93

CC1CC(CC(O)CCC(N)=C(C)C(O)=O)CCC1N

not identified

1.42E-03

-0.14

31

not identified

89

94

CC=C(N)CCC(O)CC1CCC(N)C(C)C1

not identified

1.13E-03

2.25

30

not identified

90

95

CC=C(N)CCC(O)CC1CCC(=O)C(C)C1

not identified

1.88E-03

1.74

46

not identified

91

96

CC1CC(CC2CCC(N)C(C)OC2=O)CCC1N

not identified

6.36E-04

1.60

29

not checked

92

97

CC1CC(CC(CCC(N)C(C)O)C(O)=O)CCC1N

not identified

1.56E-03

-1.69

30

not identified

93

98

CC1CC(CC(CCC(N)C(C)=O)C(O)=O)CCC1N

not identified

1.13E-03

-1.44

33

not identified

94

99

CC1CC(CCCCC(N)C(C)=O)CCC1N

not identified

3.38E-04

2.58

36

not checked

95

100

CC1CC(CCCCC(N)C(C)=O)CCC1=O

not identified

1.03E-03

2.08

51

not identified

96

101

CC1CC(CCCCC(=O)C(C)=O)CCC1N

not identified

1.03E-03

1.77

52

not identified

97

102

CC1CC(CC2CC(C)C(N)COC2=O)CCC1N

not identified

6.36E-04

1.60

35

not checked

98

103

CC1CC(CC(CC(C)C(N)CO)C(O)=O)CCC1N

not identified

1.63E-03

-1.69

38

not identified

99

104

CC(CCCC1CCC(N)C(C)C1)C(N)CO

not identified

4.87E-04

2.33

37

not checked

100

105

CC(CCCC1CCC(N)C(C)C1)C(=O)CO

not identified

1.49E-03

2.74

44

not identified

101

106

CC(CCCC1CCC(=O)C(C)C1)C(N)CO

not identified

1.49E-03

1.83

56

not identified

102

107

CC1CC(CC2CC(C)C(N)C(=O)OC2)CCC1N

not identified

8.07E-04

1.60

34

not checked

103

108

CC1CC(CC2CC(C)C(N)C(=O)OC2)CCC1=O

not identified

2.46E-08

1.10

50

not checked

104

109

CC1CC(CC2(O)CCC(=O)C(C)C2)COC(=O)C1N

not identified

2.46E-08

-0.41

48

not checked

105

110

CC1CC(CC2(O)CCC(=O)OC(C)C2)COC(=O)C1N

not identified

2.73E-04

-0.86

47

not checked

106

111

CC1CC(CC(O)(CCC(O)=O)CC(C)O)COC(=O)C1N

not identified

2.19E-08

-3.74

54

not checked

107

112

CC1CC(CC(O)(CC(C)O)C=CC(O)=O)COC(=O)C1N

not identified

2.19E-08

-2.46

54

not checked

108

113

CC1CC(CC(O)(CC(C)O)C(O)CC(O)=O)COC(=O)C1N

not identified

2.19E-08

-5.28

53

not checked

109

114

CC1CC(CC(O)(CC(C)O)C(=O)CC(O)=O)COC(=O)C1N

not identified

2.19E-08

-4.87

53

not checked

110

115

CC1CC(CC(O)(CC(C)O)C(O)=O)COC(=O)C1N

not identified

6.72E-04

-4.41

45

not checked

111

116

CC1CC(CC(O)(CC(C)=O)C(O)=O)COC(=O)C1N

not identified

1.52E-03

-5.33

55

not identified

112

117

CC1CC(CC2CC(C)C(=O)C(=O)OC2)CCC1N

not identified

2.73E-04

3.13

42

not checked

113

118

CC1CC(CC(CC(C)C(=O)C(O)=O)CO)CCC1N

not identified

2.19E-08

1.23

42

not checked

114

119

CC1CC(CC(CC(C)C(=O)C(O)=O)C=O)CCC1N

not identified

2.19E-08

1.21

42

not checked

115

120

CC1CC(CC(CC(C)C(=O)C(O)=O)C(O)=O)CCC1N

not identified

2.25E-04

-2.32

40

not checked

116

121

CC(CCCC1CCC(N)C(C)C1)C(=O)C(O)=O

not identified

9.82E-04

2.28

43

not checked

117

122

CC1CC(CC(CC(C)C=O)C(O)=O)CCC1N

not identified

9.82E-04

-0.66

55

not checked

118

123

CC1CC(CC2CC(C)C(N)OC(=O)C2)CCC1N

not identified

6.36E-04

3.35

40

not checked

119

124

CC1CC(CC(CC(C)C(N)O)CC(O)=O)CCC1N

not identified

5.09E-08

-1.69

43

not checked

120

125

CC1CC(CC(CC(C)C=O)CC(O)=O)CCC1N

not identified

5.09E-08

-0.17

43

not checked

121

126

CC1CC(CC(CC(C)C(O)=O)CC(O)=O)CCC1N

not identified

5.09E-08

-0.50

41

not checked

122

127

CC1CC(CC(O)(CC(C)C(O)=O)CC(O)=O)CCC1N

not identified

6.66E-04

-2.01

39

not checked

123

128

CC1CC(CC(O)(CC(O)=O)C=C(C)C(O)=O)CCC1N

not identified

5.79E-04

-2.09

47

not checked

124

129

CC1CC(CC(O)(CC(O)=O)C(O)C(C)C(O)=O)CCC1N

not identified

5.03E-04

-3.14

44

not checked

125

130

CC1CC(CC(O)(CC(O)=O)C(O)=C(C)C(O)=O)CCC1N

not identified

3.35E-08

-2.57

55

not checked

126

131

CC1CC(CC(O)(CC(O)=O)C(=O)C(C)C(O)=O)CCC1N

not identified

4.38E-04

-3.14

55

not checked

127

132

CC1CC(CC(O)(CC(O)=O)C(O)=O)CCC1N

not identified

9.33E-04

-2.79

50

not checked

128

133

CC1CC(CC(=O)CC(O)=O)CCC1N

not identified

1.98E-03

-2.55

64

not identified

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) DMDC is completely in the parametric, the metabolic and the structural domain (100%). The model was used to predict potential metabolites.

- The model predicts a BOD value of 39% for DMDC, supporting the result of the experimental data that the substance is not readily biodegradable. 

- 26 of the 37 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 30% to 59% after 28 days (based on BOD).

- Eleven of the relevant metabolites were estimated to be readily biodegradable (threshold value: ≥60%), with individually calculated biodegradation values between 62% and 93% after 28 days (based on BOD).

In conclusion, 70% 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 30% of the relevant metabolites are predicted to be readily biodegradable.

The degradation products of DMDC (CAS-# 6864 -37 -5) 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 DMDC (CAS-# 6864 -37 -5) a log Kow of 4.1, which exceeds the experimentally determined log Kow of 2.3. Both values do not fulfill the screening criterion for B/vB substances.

Without exception, all of the 128 modelled degradation products of DMDC were estimated to exhibit log Kow values of ≤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 DMDC are concluded to be “not B” and “not vB”.

 

Toxicity (“T”):

As the predicted degradation products do not 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 DMDC.

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, 26 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.
Likely routes of exposure:

Dermal, inhalation