N,N,N',N'-tetramethylhexamethylenediamine

Bioaccumulation: aquatic / sediment

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

 

For the assessment of N,N,N',N'-Tetramethylhexamethylenediamine (TMHDA, CAS 111 -18 -2) (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.

Parent compound:

No studies are available for the bioaccumulation assessment of the substance. According to Regulation (EC) 1907 (2006) Annex IX, Section 9.3.2, Column 2, a study on bioaccumulation does not need to be conducted as the substance has a low potential for bioaccumulation. The substance has an experimentally determined log Kow of 1.99 (23 °C, pH 12; BASF SE, 2013, report no.: 11L00324, see IUCLID Ch. 4.7). Regarding this value, accumulation of the test substance in organisms is not to be expected. Therefore, and for reasons of animal welfare, a study on bioaccumulation is not provided.

 

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)

Model	BCF [L/kg]	In AD	Remarks
BCF base-line model v.03.10 (OASIS Catalogic v5.13.1.156): incl. mitigating factors	2.45	yes	-
BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation	3.4	no	The substance ionizes at physiologically relevant pH.
BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)	9.55	yes	-
US EPA T.E.S.T. v4.2.1: Bioaccumulation: Consensus method	9.92	yes	Based on the mean absolute errors of the models the confidence in the predicted results is high.
BCFBAF v3.01 (EPI Suite v4.11): Arnot-Gobas BCF, upper trophic, incl. biotransformation of zero	11.3	no	The substance ionizes at physiologically relevant pH.
BCF baseline model v.03.10 (OASIS Catalogic v5.13.1.156): not considering mitigating factors	39.6	yes	-

 

Considering all models applied the estimated BCF values range from 2.45 to 39.6 L/kg.

According to the BCF base-line v03.10 model, metabolism is the major mitigating factor for reducing the bioaccumulation potential of N,N,N',N'-tetramethylhexamethylenediamine (CAS 111 -18 -2). The relevant phase I reactions identified by the model are the following biotransformations: aliphatic N-oxidation, aliphatic C-hydroxylation and to a minor extent N-dealkylation.

Predicted metabolites from Catalogic 301C v11.15 (OASIS Catalogic v5.13.1.156):

Metabolites (n = 29) from the degradation of N,N,N',N'-tetramethylhexane-1,6-diamine (CAS 111-18-2) were predicted using the QSAR model Catalogic 301C v11.15. The metabolites are identified by their SMILES code. The table below also lists the estimated quantity of appearance from the degradation as well as the log Kow and the biodegradability (BOD prediction). The metabolites with a quantity of > 0.001 mol/mol parent (approx. 0.1%) are regarded to be relevant for the environmental assessment. It was attempted to identify the relevant metabolites either via the QSAR Toolbox and/or the advanced search option for substances on the ECHA website. In case a name and/or CAS number was assigned, the PBT/vPvB status according to the ECHA website was checked.

Based on the available information, it can be concluded that all metabolites have a log Kow < 3. 16 of the 29 metabolites have a predicted quantity of > 0.001 mol/mol parent and are regarded as relevant for further assessment. The majority of these metabolites (11/16) are not readily biodegradable (< 60% after 28 days, based on BOD), but all of these 16 metabolites have a log Kow < 3; therefore, a significant bioaccumulation potential is not expected. It can be concluded that these substances are not PBT/vPvB substances.

Their toxicity (T) was not further assessed as no critical combination of potential P/vP (= not readily biodegradable) and potential B/vB (log Kow > 3) properties was observed.

 

Table 3: QSAR prediction for CAS-#111-18-2 using CATALOGIC 301C v11.15 – July 2018 (OASIS CATALOGIC v5.13.1.156; metabolites with a quantity > 0.001 mol/mol parent (approx. 0.1%) 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 v5.13.1.156))

#	Metabolite (no)	SMILES	Substance name (CAS)	Quantity (mol/mol parent)	Log Kow	BOD prediction (% after 28 d)	PBT-Assessment: ECHA (disseminated substances)
parent	1	CN(C)CCCCCCN(C)C	N,N,N',N'-tetramethylhexane-1,6-diamine (CAS 111-18-2)	0.683	1.70	8	not PBT/vPvB
1	15	C=O	Formaldehyde (CAS 50-00-0)	0.0063	0.35	100	not PBT/vPvB
2	2	CNCCCCCCN(C)C	1,6-Hexanediamine, N,N,N'-trimethyl- (CAS 1862-11-9)	0.0266	1.49	36	not registered under REACH
3	22	CN(C)CCCCCCN(C)CO	not identified	0.1016	0.24	8	not identified
4	16	OC=O	Formic acid (CAS 64-18-6)	3.87E-06	-0.46	100	not checked
5	14	CN	Methanamine (CAS 74-89-5)	0.0349	-0.64	64	not PBT/vPvB
6	3	CN(C)CCCCCC=O	Hexanal, 6-(dimethylamino)- (CAS 2554-94-1)	0.0035	1.00	37	not registered under REACH
7	21	CN(C)CCCCCCN	1,6-Hexanediamine, N,N'-dimethyl- (CAS 13093-04-4)	0.0326	1.02	29	not registered under REACH
8	23	CN(C)CCCCCCNCO	not identified	0.0019	0.02	36	not identified
9	25	CNCCCCCCN(C)CO	not identified	0.0019	0.02	37	not identified
10	4	CN(C)CCCCCC(O)=O	Hexanoic acid, 6-(dimethylamino)- (CAS 1072-09-9)	1.38E-06	-1.94	34	not checked
11	24	NCO	Cyanooxy (CAS 22400-26-6)	5.668E-08	-2.10	100	not checked
12	26	CN(CCCCCC=O)CO	not identified	0.0035	-0.46	39	not identified
13	33	CN(CCCCCCN)CO	not identified	0.0021	-0.44	30	not identified
14	5	CN(C)CCCC=CC(O)=O	not identified	1.38E-06	-0.66	34	not checked
15	27	CN(CCCCCC(O)=O)CO	not identified	5.667E-08	-3.41	36	not checked
16	6	CN(C)CCCC(O)CC(O)=O	not identified	1.38E-06	-3.48	31	not checked
17	28	CN(CCCC=CC(O)=O)CO	not identified	5.667E-08	-2.12	36	not checked
18	7	CN(C)CCCC(=O)CC(O)=O	not identified	1.38E-06	-3.99	31	not checked
19	29	CN(CCCC(O)CC(O)=O)CO	not identified	5.667E-08	-4.54	33	not checked
20	8	CN(C)CCCC(O)=O	Butanoic acid, 4-(dimethylamino)- (CAS 693-11-8)	0.1226	-2.92	8	not registered under REACH
21	20	CC(O)=O	Acetic acid (CAS 64-19-7)	1.43E-06	0.09	100	not checked
22	30	CN(CCCC(=O)CC(O)=O)CO	not identified	5.667E-08	-5.46	33	not checked
23	9	CNCCCC(O)=O	Butanoic acid, 4-(methylamino)- (CAS 1119-48-8)	0.0026	-3.14	66	not registered under REACH
24	31	CN(CCCC(O)=O)CO	not identified	0.0051	-4.39	9	not identified
25	10	OC(=O)CCC=O	Butanoic acid, 4-oxo- (CAS 692-29-5)	0.0015	-0.42	91	not registered under REACH
26	19	NCCCC(O)=O	2-Butynoic acid, 4-amino- (CAS 56-12-2)	0.0023	-3.60	57	not PBT/vPvB
27	32	OCNCCCC(O)=O	not identified	6.18E-04	-4.60	68	not checked
28	11	OC(=O)CCC(O)=O	Butanedioic acid (CAS 110-15-6)	8.80E-04	-0.75	90	not checked
29	12	CCC(O)=O	Propanoic acid (CAS 79-09-4)	0.0077	0.58	100	not PBT/vPvB

Based on the available information on the log Kow (log Kow = 1.99; measured; BASF SE 2013, report no. 11LL00324, see IUCLID Ch. 4.7) and supported by a weight-of-evidence approach from calculated data, it can be concluded that N,N,N',N'-tetramethylhexane-1,6-diamine and its metabolites are not expected to exhibit a significant bioaccumulation potential.