Reaction product of 2,4-Dinitrotoluene and 2,6-Dinitrotoluene and hydrogen

Bioaccumulation: aquatic / sediment

Description of key information

Significant accumulation of the substance (EC 939-489 -9) 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 the reaction product of 2,4-Dinitrotoluene and 2,6-Dinitrotoluene and hydrogen (EC 939-489-9; MCDA) (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:

The substance is a reaction product of 2,4-Dinitrotoluene and 2,6-Dinitrotoluene and hydrogen and contains 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7; ca. 70-90%) and 2-methylcyclohexane-1,3-diamine (CAS 13897-56-8; ca. 10-30%). 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 0.12 (@ 23 °C, pH 12; BASF SE; 2011; report no. 11L00071, see IUCLID Ch. 4.7).

Regarding these values, accumulation of the 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 substance, the BCF was calculated for the two representative constituents of the reaction product (2-methylcyclohexane-1,3-diamine CAS 13897-56-8 and 4-methylcyclohexane-1,3-diamine, CAS 13897-55-7) 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) for both constituents. 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.

 

Table 1: Summary of relevant information on aquatic bioaccumulation: Predicted BCF values for applied QSAR models sorted by BCF:

(AD = Applicability Domain)

Model	Conditions	BCF [L/kg]	In AD	Restraints
CAS 13897-55-7
BCFBAF v3.01 (EPI Suite v4.11):Arnot-GobasBCF	Uncharged molecule; upper trophic, incl. biotransformation	1.025	no	The substance appreciably ionizes at physiologically relevant pH
BCFBAF v3.01 (EPI Suite v4.11):Arnot-GobasBCF	Uncharged molecule; upper trophic, incl. biotransformation of zero	1.034	no	The substance appreciably ionizes at physiologically relevant pH
US EPA T.E.S.T. v4.2.1: Bioaccumulation: Consensus method		2.87	yes	Based on the mean absolute errors of the models the confidence in the predicted results is low.
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; at pH 7	2.29	yes	-
BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)	Uncharged molecule	3.16	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; log Kow experimental	3.47	yes	-
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; at pH 12	3.72	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; log Kow calculated	4.17	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; log Kow experimental	10.4	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; log Kow calculated	11.5	yes	-
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; at pH 7	11.5	yes	-
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; at pH 12	11.5	yes	-
CAS 13897-56-8
BCFBAF v3.01 (EPI Suite v4.11): Arnot-GobasBCF	Uncharged molecule; upper trophic, incl. biotransformation	1.025	no	The substance appreciably ionizes at physiologically relevant pH
BCFBAF v3.01 (EPI Suite v4.11):Arnot-GobasBCF	Uncharged molecule; upper trophic, incl. biotransformation of zero	1.034	No	The substance appreciably ionizes at physiologically relevant pH
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; at pH 7	2.34	yes	-
BCFBAF v3.01 (EPI Suite v4.11): Meylan et al. (1997/1999)	Uncharged molecule	3.16	yes	-
US EPA T.E.S.T. v4.2.1: Bioaccumulation: Consensus method		3.61	yes	Based on the mean absolute errors of the models the confidence in the predicted results is low.
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; log Kow experimental	3.8	yes	-
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; at pH 12	4.47	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	incl. mitigating factors; log Kow calculated	4.79	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; log Kow experimental	10.4	yes	-
BCF base-line model v04.11 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; log Kow calculated	11.5	yes	-
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; at pH 7	11.5	yes	-
BCF base-line model DP v01.06 (OASIS Catalogic v5.14.1.2)	not considering mitigating factors; at pH 12	11.5	yes	-

 

Considering all models applied for both constituents, the estimated BCF values range from 1.03 to 11.5 L/kg.

According to the BCF base-line model v04.11 (Catalogic v5.14.1.2), metabolism is a minor mitigating factor for reducing the bioaccumulation potential of the representative constituents of the reaction product (CAS 13897-55-7 and CAS 13897-56-8). The BCF base-line model identified aliphatic C-Oxidation as the relevant phase I reaction for 4 -methylcyclohexane-1,3 -diamine (CAS 13897 -55 -7), but none for 2 -methylcyclohexane-1,3 -diamine (CAS 13897 -56 -8).

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

Metabolites (n = 86) from the degradation of 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7) and 47 metabolites from the degradation of 2-methylcyclohexane-1,3-diamine (CAS 13897-56-8) 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). In the table below only those metabolites with a quantity of > 0.001 mol/mol parent (approx. 0.1%) are listed, as they are regarded to be relevant for the environmental assessment (for further details see corresponding study entries, IUCLID Ch. 5.2.1). 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. 9 of the 86 metabolites of 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7) and 10 of the 47 metabolites of 2-methylcyclohexane-1,3-diamine (CAS 13897-56-8) have a predicted quantity of > 0.001 mol/mol parent and are regarded as relevant for further assessment. Half of these metabolites (9/19) are not readily biodegradable (< 60% after 28 days, based on BOD), but all of these 19 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 2: QSAR prediction for CAS-#13897-55-7 and CAS-#13897-56-8 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)	LogKow	BOD prediction (% after 28 d)	PBT-Assessment (ECHA (disseminated substances)
parent	1	CC1CCC(N)CC1N	4-methylcyclohexane-1,3-diamine (CAS 13897-55-7)	0.132	0.12	55	Not PBT/vPvB
1	2	CC1CCC(N)CC1=O	3-amino-6-methylcyclohexanone	0.155	-0.001	63	No results were found.
2	15	CC1CCC(=O)CC1N	3-amino-4-methylcyclohexanon (CAS 2138125-40-1)	0.155	-0.001	62	No results were found.
7	63	CC1CCC(N)C(=O)OC1N	3,7-diamino-6-methyl-oxepan-2-one	0.0011	-0.2457	63	No results were found.
8	75	CC1CCC(N)OC(=O)C1N	3,7-diamino-4-methyl-oxepan-2-one	0.0011	-0.2457	58	No results were found.
20	18	NC1CCC(C(O)=O)C(N)C1	2,4-diaminocyclohexancarboxylic acid	0.0034	-3.933	55	No results were found.
29	19	NC1CCC(C(O)=O)C(=O)C1	4-amino-2-oxocyclohexane-1-carboxylic acid	0.0014	-4.438	72	No results were found.
30	27	NC1CC(=O)CCC1C(O)=O	6-amino-4-oxocyclohexane-1-carboxylic acid	0.0039	-4.438	56	No results were found.
71	24	NC(CC(O)=O)CC(O)=O	3-aminopentanedioic acid (CAS 1948-48-7)	0.003418	-5.008	62	No results were found.
80	73	CCC(O)=O	propionic acid (CAS 79-09-4)	0.001625	0.578	100	Not PBT/vPvB
parent	1	CC1C(N)CCCC1N	2-methylcyclohexane-1,3-diamine (CAS 13897-56-8)	0.13	0.12	50	Not PBT/vPvB
1	2	CC1C(N)CCCC1=O	5-amino-6-methylcyclohexanone	0.31	0.00	57	No results were found.
13	16	NC1CCCC(N)C1C(O)=O	2,6-diaminociclohexane-1-carboxylic acid	0.0035	-3.93	36	No results were found.
20	17	NC1CCCC(=O)C1C(O)=O	6-amino-2-oxocyclohexane-1-carboxylic acid	0.0079	-4.44	39	No results were found.
27	50	C=C	Ethylene (CAS 74-85-1)	0.0010	1.27	10	Not PBT/vPvB
29	18	OC(=O)C1C(=O)CCCC1=O	2,6-dioxocyclohexane-1-carboxylic acid	0.0042	-0.39	60	No results were found.
37	29	CC(C=O)C(N)CC(O)=O	3-amino-4-formyl-pentanoic acid	0.0016	-4.26	47	No results were found.
40	8	CCC(=O)OCCC(O)=O	3-(propionyloxy)propane acid (CAS 1085694-20-7)	0.058	0.61	92	No results were found.
43	40	CCC(N)=CC	pent-1-en-3-amine (CAS 70267-50-4)	0.0014	1.17	17	No results were found.
46	21	OCC(=O)CCCC(O)=O	6-hydroxy-5-oxohexanoic acid (CAS 497844-76-5)	0.0040	-0.55	100	No results were found.
47	23	OCCCC(=O)CC(O)=O	3-oxo-6-hydroxyhexanoic acid	0.0040	-1.46	94	No results were found.

 

Based on the available information on the log Kow (log Kow= 0.12; measured for MCDA; BASF SE, 2011, report no.: 11L00071) and supported by a weight-of-evidence approach from calculated data, it can be concluded that significant accumulation of MCDA (EC 939-489 -9) in organisms is not to be expected.