2-piperazin-1-ylethanol

PBT assessment

PBT assessment: overall result

Reference

Name:

N-Hydroxyethylpiperazine

Type of composition:

boundary composition of the substance

State / form:

liquid

Reference substance:

N-Hydroxyethylpiperazine

PBT status:

the substance is not PBT / vPvB

Justification:

PBT / vPvB - Assessment for the parent compound 2-piperazine-1-ylethanol (CAS 103-76-4):

Following a weight-of-evidence approach, 2-piperazine-1-ylethanol (CAS 103-76-4) is not readily biodegradable (according to OECD criteria). In a marine ready biodegradability test the substance was degraded to < 10% after 28 d (based on O2 consumption, Eide-Haugmo et al., 2009). In addition, the substance is calculated to be poorly degraded by three estimation models (degradation ranges from 9 to 28% within 28 days; BASF SE, 2020). Therefore, 2-piperazine-1-ylethanol should be assessed P from a precautionary point of view.

The log Kow (-1.47 at 25 °C, pH 10.5-10.9, BASF AG, 1989, report no.: 105629) as well as several QSAR calculations (calculated BCF values range between 0.9 L/kg and 9.23 L/kg, BASF SE 2015, 2016, 2020) indicate no potential for bioaccumulation (not B/vB).

The substance is not toxic (not T) since the lowest NOEC is > 0.01 mg/L (daphnids, 21-d NOEC reproduction >= 12 mg/L, BASF SE 2019, report no.: 51E0573/15E065) and it holds no relevant classification.

In conclusion, the substance is considered to be not PBT / not vPvB.

 

PBT / vPvB - Assessment for modelled metabolites of 2-piperazine-1-ylethanol (CAS 103-76-4):

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 2-piperazine-1-ylethanol 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 CATALOGIC 301C v11.15 calculated 20 metabolites (Table 1) identifying 7 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: 0.001-2 [mol/mol parent]).

 

Table 1: QSAR prediction for CAS 103-76-4 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 v5.13.156))

#	Metabolite No	Smiles	Substance name (CAS)	Quantity (mol/mol parent)	LogKow	BOD prediction (% after 28 d)	PBT-Assessment (ECHA (disseminated substances)
parent	1	OCCN1CCNCC1	2-piperazin-1-ylethanol (CAS 103-76-4)	0.000010	-1.47	28	not checked
1	2	O=CCN1CCNCC1	not identified	0.000010	-1.586	28	not checked
2	3	OC(=O)CN1CCNCC1	2-piperazin-1-ylacetic acid	0.006192	-3.357	22	not (pre-)registered
3	4	OC(=O)C=O	Glyoxylic acid (CAS 298-12-4)	0.007177	-1.403	100	not PBT / vPvB
4	8	C1CNCCN1	Piperazine (CAS 110-85-0)	0.975300	-0.799	1	not PBT / vPvB
5	15	OC1CNCCN1CC(O)=O	not identified	0.000000	-3.897	81	not checked
6	18	OC(C(O)=O)N1CCNCC1	not identified	0.000030	-3.585	15	not checked
7	19	OC1CN(CC(O)=O)CCN1	not identified	0.000002	-3.897	58	not checked
8	5	OC(=O)C(O)=O	not identified	0.000010	-1.736	100	not checked
9	9	OC1CNCCN1	not identified	0.000052	-2.337	75	not checked
10	16	OC(=O)CNCCNCC=O	not identified	0.000000	-4.454	81	not checked
11	20	NCCN(CC=O)CC(O)=O	not identified	0.000000	-4.709	22	not checked
12	10	NCCNCC=O	not identified	0.000000	-2.151	76	not checked
13	17	OC(=O)CNCCNCC(O)=O	not identified	0.000046	-4.788	80	not checked
14	21	NCCN(CC(O)=O)CC(O)=O	not identified	0.000898	-4.043	14	not checked
15	11	NCCNCC(O)=O	2-(2-aminoethylamino)acetic acid	0.007845	-3.922	73	not (pre-)registered
16	22	OC(=O)CN(CC=O)CC(O)=O		0.000000	-4.061	11	not checked
17	12	NCCN	1,2-Ethanediamine (CAS 107-15-3)	0.001139	-1.618	67	not PBT / vPvB
18	23	OC(=O)CN(CC(O)=O)CC(O)=O	2-[bis(carboxymethyl)amino]acetic acid	0.001473	-3.809	2	not (pre-)registered
19	13	NCC=O	2-aminoacetaldehyde	0.006952	-1.637	72	not (pre-)registered
20	24	OC(=O)CNCC(O)=O	not identified	0.000023	-3.274	81	not checked

 

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) 2-piperazine-1-ylethanol is in the parametric, the structural and the metabolic domain (100%).

- The model was used to predict potential metabolites.

- 3 of the 7 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 1% to 22% after 28 days (based on BOD).

- The remaining 4 relevant metabolites were estimated to be readily biodegradable (threshold value: ≥60%), with individually calculated biodegradation values between 67% and 100% after 28 days (based on BOD).

In conclusion, 43% of the predicted metabolites present in concentration of ≥0.1% (equivalent to quantity setting in OASIS CATALOGIC: 0.001-2 [mol/mol parent]) are estimated to be not readily biodegradable while 57% of the relevant metabolites are predicted to be readily biodegradable.

The 3 degradation products of 2-piperazine-1-ylethanol (CAS 103-76-4) which are predicted as not readily biodegradable metabolites should be considered as potentially P/vP from a precautionary point of view, until further data become available.

 

Bioaccumulation (“B/vB”):

In a test according to OECD 107 a log Kow of -1.47 at 25 °C and pH 10.5-10.9 was measured for 2-piperazine-1-ylethanol (BASF AG, 1989, report no.: 105629, see IUCLID Ch. 4.7). This indicates a low potential for bioaccumulation.

Without exception, all the 20 modelled degradation products of 2-piperazine-1-ylethanol 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 2-piperazine-1-ylethanol are concluded to be “not B” and “not vB”.

 

Toxicity (“T”):

Considering potential “T” properties, limited data are available for the relevant metabolites of the parent compound 2-piperazine-1-ylethanol. Only few of the relevant metabolites of the CATALOGIC model are registered under REACH. None of these substances were assessed to fulfill the criteria for “T”. Based on the available data on the persistence and bioaccumulation potential of all of the relevant metabolites, it can be concluded that all relevant degradation products do neither fulfill the PBT criteria (not PBT) nor the vPvB criteria (not vPvB).

 

Overall conclusion:

1.  Sufficient test data are available to assess the PBT/vPvB properties of 2-piperazine-1-ylethanol.

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

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

2b. However, 3 predicted relevant metabolites present in concentration of ≥0.1% (equivalent to quantity setting in OASIS Catalogic: 0.001-2 [mol/mol parent]; CATALOGIC 301C v11.15) should be considered as potentially P/vP from a precautionary point of view.