4,4'-methylenebis(cyclohexylamine)

PBT assessment

PBT assessment: overall result

PBT status:

the substance is not PBT / vPvB

Justification:

 

PBT / vPvB - Assessment for the parent compound

Based on the results and evidence set up in the PBT endpoint study record, it can be concluded that the substance is considered to be potentially P/vP, from a precautionary point of view.

The substance is not B/vB based on logKow 2,03 for the substance. QSAR models indicate that significant bioaccumulation is not to be expected: BCF values calculated are 10.1 using BCFBAF v3.01 and 21.7 using Catalogic v5.11.6TB - BCF baseline model v02.05 considering effective mitigating factors like molecular size and water solubility.

The substance is neither chronically nor acutely toxic to aquatic organisms. The lowest chronic value is clearly greater than 0.01 mg/L. However, the substance is classified as STOT-RE, target organs: skeletal muscle and liver, for vacuolar degeneration identified by histopathology (STOT Rep. Exp. 2; H373); therefore, the substance is assessed to be T.

 

 

Overall, the substance is P from a precautionary point of view but unlikely vP, and T, but not B/vB, therefore it can be concluded that the substance is not PBT or vPvB.

 

PBT / vPvB – Assessment for modelled metabolites of 4,4'-methylene-dicyclohexanamine (CAS 1761-71-3):

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 4,4'-methylene-dicyclohexanamine (CAS 1761-71-3) 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 v11.16 (OASIS CATALOGIC v5.14.1.5).

Overall, the CATALOGIC 301C v11.16 calculated 77 metabolites (Table 1) identifying 15 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: QSAR prediction for CAS 1761-71-3 using CATALOGIC 301C v11.16 (OASIS CATALOGIC v5.14.1.5; 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 v11.16)

 

#	Metabolite (no)	Smiles	Quantity (mol/mol parent)	LogKow	BOD prediction (% after 28 d)
1	11	NC1CCC(CC(O)(CC(O)=O)C(O)=O)CC1	0,2413	-3	53
2	23	C=C	0,1722	1	10
3	14	NC1CCC(O)(CC(O)=O)CC1	0,1639	-3	55
4	parent	NC1CCC(CC2CCC(N)CC2)CC1	0,1358	2	42
5	15	NC1CCC(=O)CC1	0,1302	-0,419	38
6	3	NC1CCC(CC2CCC(=O)OCC2)CC1	0,09323	2	61
7	17	O=C1CCC(=O)CCO1	0,02389	0,434	53
8	19	OC(=O)CCC(O)=O	0,01969	-0,754	90
9	42	NC1CCC(CCC(O)=O)CC1	0,002273	-1	67
10	56	NC1CCC(CC(CCC(N)CO)C(O)=O)CC1	0,001727	-3	60
11	68	NC1CCC(CC=O)CC1	0,001571	1	60
12	54	NC1CCC(CC(=O)CC(O)=O)COC1=O	0,001571	-5	73
13	58	NC(CCCCC1CCC(=O)CC1)CO	0,001571	0,99	74
14	59	NC1CCC(CCCCC(=O)CO)CC1	0,001571	2	76
15	16	O=C1CCC(=O)CC1	0,001552	-0,924	56
16	79	NC(CCC(O)CC(=O)CC(O)=O)CC(O)=O	0,001396	-6	82
17	32	NC1CCC(CC2CCC(N)C(=O)OC2)CC1	0,0008525	0,766	52
18	61	NC1CCC(CC(O)CCC(N)CC(O)=O)CC1	0,0007579	-3	47
19	67	NC1CCC(CC(O)C(O)=O)CC1	0,0007417	-3	51
20	53	NC1CCC(CC(O)(CC(O)=O)C(O)=O)COC1=O	0,0007417	-6	59
21	80	NC1CCC(CC2CCC(N)OC(=O)C2)CC1	0,000672	3	59
22	60	NC1CCC(CC2CCC(N)CC(=O)O2)CC1	0,000672	0,766	51
23	55	NC1CCC(CC2CCC(N)COC2=O)CC1	0,000672	0,766	53
24	78	NC(CCC(O)CC(O)(CC(O)=O)C(O)=O)CC(O)=O	0,0006594	-5	63
25	57	NC(CCCCC1CCC(N)CC1)CO	0,0005148	1	58
26	33	NC1CCC(CC2CCC(=O)C(=O)OC2)CC1	0,0002887	2	78
27	45	NC1CCC(CC2CCC(=O)OCC2)COC1=O	0,0002887	-0,1892	68
28	70	NC(CCC(O)CC1CCC(=O)OCC1)CC(O)=O	0,0002567	-3	67
29	41	NC1CCC(CC(C(O)=O)C(O)=O)CC1	3,95E-05	-3	71
30	49	NC1CCC(CC(CC(O)=O)C=CC(O)=O)COC1=O	0	-4	69
31	62	NC1CCC(CC(O)CCC(=O)CC(O)=O)CC1	0	-3	68
32	34	NC1CCC(CC(CCC(=O)C(O)=O)CO)CC1	0	0,399	78
33	38	NC1CCC(CC(C=CC(O)=O)C(O)=O)CC1	0	-2	77
34	9	NC1CCC(CC(CC(O)=O)C(=O)CC(O)=O)CC1	0	-3	62
35	66	NC1CCC(CC(O)C(=O)CC(O)=O)CC1	0	-3	60
36	2	NC1CCC(CC2CCC(=O)CC2)CC1	0	3	62
37	4	NC1CCC(CC(CCC(O)=O)CCO)CC1	0	-0,98	65
38	81	NC1CCC(CC(CCC(N)O)CC(O)=O)CC1	0	-3	65
39	82	NC1CCC(CC(CCC=O)CC(O)=O)CC1	0	-1	65
40	69	NC(CCC(O)CC1CCC(=O)CC1)CC(O)=O	0	-3	68
41	44	NC1CCC(CC2CCC(=O)CC2)COC1=O	0	0,2604	69
42	65	NC1CCC(CC(O)C(O)CC(O)=O)CC1	0	-3	60
43	64	NC1CCC(CC(O)C=CC(O)=O)CC1	0	-0,677	62
44	47	NC1CCC(CC(CCC(O)=O)CC=O)COC1=O	0	-4	70
45	48	NC1CCC(CC(CCC(O)=O)CC(O)=O)COC1=O	0	-4	69
46	37	NC1CCC(CC(CCC(O)=O)C(O)=O)CC1	0	-2	77
47	72	NC(CCC(O)CC(CCC(O)=O)CC=O)CC(O)=O	0	-4	73
48	73	NC(CCC(O)CC(CCC(O)=O)CC(O)=O)CC(O)=O	0	-4	72
49	50	NC1CCC(CC(CC(O)=O)C(O)CC(O)=O)COC1=O	0	-5	68
50	39	NC1CCC(CC(C(O)CC(O)=O)C(O)=O)CC1	0	-3	76
51	8	NC1CCC(CC(CC(O)=O)C(O)CC(O)=O)CC1	0	-3	62
52	71	NC(CCC(O)CC(CCC(O)=O)CCO)CC(O)=O	0	-4	73
53	10	NC1CCC(CC(CC(O)=O)C(O)=O)CC1	0	-2	55
54	63	NC1CCC(CC(O)CCC(O)=O)CC1	0	-2	62
55	28	OC(=O)C=O	0	-1	100
56	52	NC1CCC(CC(CC(O)=O)C(O)=O)COC1=O	0	-5	61
57	40	NC1CCC(CC(C(=O)CC(O)=O)C(O)=O)CC1	0	-4	76
58	26	OCC=O	0	-2	100
59	27	OCC(O)=O	0	-1	100
60	18	C=CC(=O)CCC(O)=O	0	0,1537	60
61	24	C1CO1	0	-0,0454	100
62	12	NC1CCC(CC(=O)CC(O)=O)CC1	0	-3	66
63	75	NC(CCC(O)CC(CC(O)=O)C(O)CC(O)=O)CC(O)=O	0	-5	71
64	51	NC1CCC(CC(CC(O)=O)C(=O)CC(O)=O)COC1=O	0	-6	68
65	74	NC(CCC(O)CC(CC(O)=O)C=CC(O)=O)CC(O)=O	0	-4	72
66	29	OC(=O)C(O)=O	0	-2	100
67	6	NC1CCC(CC(CCC(O)=O)CC(O)=O)CC1	0	-1	64
68	31	CC(O)=O	0	0,0868	100
69	35	NC1CCC(CC(CCC(=O)C(O)=O)C=O)CC1	0	0,3744	78
70	46	NC1CCC(CC(CCC(O)=O)CCO)COC1=O	0	-3	70
71	36	NC1CCC(CC(CCC(=O)C(O)=O)C(O)=O)CC1	0	-3	78
72	7	NC1CCC(CC(CC(O)=O)C=CC(O)=O)CC1	0	-2	64
73	76	NC(CCC(O)CC(CC(O)=O)C(=O)CC(O)=O)CC(O)=O	0	-6	71
74	13	NC1CCC(CC(O)=O)CC1	0	-2	58
75	25	OCCO	0	-1	100
76	5	NC1CCC(CC(CCC(O)=O)CC=O)CC1	0	-1	65
77	20	CCC(O)=O	0	0,578	100
78	77	NC(CCC(O)CC(CC(O)=O)C(O)=O)CC(O)=O	0	-5	64

 

Metabolites with a quantity < 0.001 mol/mol parent after 28 d are not considered being relevant for the PBT/vPvB assessment and, therefore their PBT/vPvB status and BCF value were not assessed.

 

 

Persistence (“P/vP”):

In order to assess the biodegradation potential of the relevant degradation products, the (Q)SAR models CATALOGIC 301C v11.16 was applied.    

- CATALOGIC 301C v11.16 (OASIS Catalogic v5.14.1.5) predicted for the substance 77 metabolites, identifying 15 metabolites as relevant degradation products in terms of PBT/vPvB assessment, with an estimated quantity of ≥ 0.1% (for details see ‘Attached background material’ of the respective Endpoint Study Record). Nine of the relevant metabolites were calculated to be readily biodegradable (≥ 60% after 28 days, based on BOD). The other five relevant metabolites were estimated to be not readily biodegradable (10 to 56% after 28 days, based on BOD). However, metabolite 23 (ethylene) is assessed as notP/vP (for details see ‘Any other information on results incl. tables’ of the respective Endpoint Study Record)

In conclusion, the majority of the predicted metabolites present in a concentration of ≥ 0.1% (equivalent to >=0.001 mol/mol parent) are estimated to be readily biodegradable.

The degradation products of 4,4'-methylene-dicyclohexanamine (CAS 1761-71-3) which are predicted to be not readily biodegradable (except for metabolite 23, not P/vP) should be considered as potentially P/vP from a precautionary point of view.

 

Bioaccumulation (“B/vB”):

None of the relevant modelled degradation products of the substance were estimated to exhibit log Kow values of ≥ 4.5 (see Table 1), thus they do not fulfil 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 the substance are concluded to be “not B” and “not vB”.

 

Toxicity (“T”):

As the predicted degradation products are not likely to fulfil 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 the substance.

2.  Potentially relevant degradation products were modelled using (Q)SAR model CATALOGIC 301C v11.16 (OASIS CATALOGIC v5.14.1.5):

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

2b. However, 5 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.

 

In conclusion, the substance and its relevant metabolites are not PBT/vPvB.

Likely routes of exposure:

Dermal, inhalation