Amides, C18-unsatd., N-[2-(1-piperazinyl)ethyl]

Endpoint summary

Description of key information

See additional information.

Additional information

N-[2-(piperazin-1-yl)ethyl]C18-unsaturated-alkylamide (AA-AEP) is quickly but not completely degraded in a ready biodegradability test (Ginkel 1990) and N-(2-aminoethyl)piperazine (AEP; CAS no 140 -31 -8) is observed to be formed as metabolite (Geerts 2014). The available biodegradability data show that AA-AEP is not persistent but only its expected degradation product AEP is considered to be persistent (Dow, 2010).

 

In a sediment water biodegradation simulation study according to OECD TG 309 using the C18-unsaturated, diamide with [14C]1-piperazineethanamine as realistic worst-case representative for AA-AEP a mean half-life of 4.5 days at 12 °C was observed and Piperazin-1-yl-acetic acid (CAS no 37478-58-3) was identified as persistent metabolite. The results are in line with what was observed in the study from Geerts and van Ginkel but only Piperazin-1-yl-acetic acid instead of AEP was found as metabolite. Under the OECD 309 test conditions AEP is apparently a step further degraded to Piperazin-1-yl-acetic acid.

 

In addition, an STP simulation study according to OECD 303A was performed and this test showed >99.99% removal of AA-AEP in an STP from which 0.042% via adsorption to sludge using specific chemical analyses based on high recoveries of spiked sludge and effluent samples (Ginkel, 2010).

In this STP simulation study also a high DOC removal of 89 ± 1% (95% confidence interval) was observed indicating that also the metabolite AEP is removed. Considering the low Henry's law constant of 9.3 * 10^-9 Atm/m3/mol. and high Koc of 37000 L/kg of AEP most of this substance is likely removed via sorption.

 

Based on the uses claimed for AA-AEP soil exposure is likely. Based on the biodegradability data from AEP and the formation of Piperazin-1-yl-acetic acid in the water-sediment biodegradation simulation study it is not expected that there will be significant further degradation in soil. Further testing in soil is therefore not expected to deliver more information. Piperazin-1-yl-acetic acid with a log Kow of -3.27 will sorb less to soil and sediment when compared to AEP which has a measured log Kow of -1.48. Piperazin-1-yl-acetic acid also has no primary amine which will certainly reduce the ionic interaction with negatively charged surfaces. 

For soil therefore a worst-case half-life value of 3000 days (Kd = 2000 L/kg) can be used for AEP and Piperazin-1-yl-acetic acid. In accordance with column 2 of REACH annex IX, further degradation testing does not need to be conducted as the chemical safety assessment does not indicate a need for further investigation.

 

The primary hydrolysis tests performed with AA-AEP indicates that the substance is hydrolyzed less than 10% within 5 days at 50°C in the pH buffers 4 and 7 but at pH9, about 23% and 13% hydrolysis was observed for the components C18:1 and C18:2, respectively. In the advanced test at pH9 at temperatures of 20, 50 and 70°C, half-lives for the C18:1 were observed of 6211, 549 and 1149 hours, respectively. For the component C18:2, half-lives were observed of 9316, 589 and 2455 hours at 20, 50 and 70°C, respectively.

Using the Arrhenius relationship, a half-life at 25°C was calculated for the two components of 3616 hours (151 days) for C18:1 component and a half-life of 4893 hours (204 days) for C18:2 component. No degradation metabolites could be identified.

 

The bioaccumulation potential of AA-AEP was not evaluated using the log Kow as the substance is a polar narcotic and there is only limited information on the relationship between log Kow and BCF for this type of substances. Performance of a standard OECD 305 test is however scientifically and ethically not considered appropriate for AA-AEP because there will be no long-term exposure and the substance will therefore not accumulate in the food-chain. The substance is either sorbed or degraded. Further bioaccumulation testing of N-[2-(piperazin-1-yl) ethyl]C18-insaturated-alkylamide (CAS no 1228186-18-2) can therefore be waived according to column 2 of REACH Annex IX.

The OECD 309 study in addition showed however, that the mineralisation of AA-AEP is not complete as a significant fraction of (Piperazin-1-yl)acetic acid (CAS no.: 37478-58-3) was observed to be remaining after 90 days of testing at 12°C.

This metabolite (Piperazin-1-yl)acetic acid is based on the available data considered persistent but has a low bioaccumulation potential based on the low calculated log Kow of -3.36 and a very high water solubility of 1000 g/L and the available bioaccumulation data on the structural analogue piperazine (CAS 110-85-0): The BCF of piperazine was determined in the carp (Cyprinus carpio), where the measured BCF was < 3.9 L/kg at 0.1 mg/L exposure (CERI, 2004).

Reference: CERI(2004). Database of Biodegradation and Bio-Accumulation Data of existing chemicals. Chemicals Evaluation and Research Institute, Japan. Available at http://www.nite.go.jp/en/chem/qsar/cscl_data.html

 

AA-AEP sorbs strongly to soils. Equilibrium adsorption coefficients (Kd's) were found to be in the range of 2300 to 4600 (cm3/g) for the C18:1 component, 1600 to 3300 for the C18:2 component and 1000 to 1900 for the C18:3 component in the different soils tested. AA-AEP is based on these sorption results considered to be immobile in soil and will not leach to ground water.

For risk assessment the average Kd of 2000 L/kg will be used and not the organic matter normalized value (Koc) because the relation between the organic matter concentration and the sorption observed alone is not sufficient (Droge & Goss, 2013).

Despite of its low log Kow and high water solubility, it is expected that similar to AEP, Piperazine acetic acid will sorb still significantly based on it ionic interaction with negatively charges surfaces. As indicated however sorption to soil will be lower.  Where AEP is not considered to be mobile in soil based on the high Koc of 37000 L/kg of AEP, Piperazin-1-yl-acetic acid may be slightly mobile in soil.

AEP has dissociation constants (pKa) of 9.6, 8.5 and 4.3 (Disseminated dossier) and is fully protonated at neutral pH. Sorption is expected to occur only based on a cation exchange mechanism and is not highly correlated with the organic carbon content in sorbents with a significant content of Cation Exchange sites not originating from organic carbon.

 

Because there is no principal difference between soil and sediments considering the sorption properties (EU-RAR Primary alkyl amines, 2008) and because the degree of sorption is not related to the organic carbon content for cationic surfactants, the value for AA-AEP for soil will also be used for sediment and suspended particles. Because suspended matter consists of smaller particles the Kd for suspended matter is as a worst-case doubled.

For sludge which consists mainly of organic matter the sorption data as observed for soil is not considered to be representative. The removal in an STP via sorption to sludge has been quantified in the STP simulation test (OECD 303A).

In the table below the distribution constants used in this assessment are summarized:  

Distribution constants 

Kpsoil	2000 L^.kg^-1	Ksoil-water	3000 m^3.m^-3
Kpsusp	4000 L^.kg^-1	Ksusp-water	1000 m^3.m^-3
Kpsed	2000 L^.kg^-1	Ksed-water	1000 m^3.m^-3