Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate

Endpoint summary

Description of key information

The registered substance “Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate” (EC No 905-983-8) is a multi-constituent substance consisting of three closely related substances. All three constituents are diesters of adipic acid contained with varying percentages. Constituent A is the dialiphatic adipate (bis(2-ethylhexyl adipate, 25 % – 35%). Constituent B is the dibenzyl adipate (dibenzyl adipate, 15 % – 25 %) and Constituent C is the mixed diester (benzyl 2-ethylhexyl adipate, 45 % – 55 %).

 

Constituents of the registered substance
bis(2-ethylhexyl) adipate Constituent A 25 % – 35 % CAS 103-23-1	dibenzyl adipate Constituent B 15 %– 25 % CAS 2451-84-5	benzyl 2-ethylhexyl adipate Constituent C 45 % – 55 % CAS 58394-64-2

 

The ready biodegradability of the test item 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' was assessed in two experimental studies (Currenta 2020 and Kanne 1989). In addition, supporting information was derived from the disseminated data of one constituent of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' (Constituent A, CAS 103-23-1) and two closely related substances (benzylbutyrat, CAS 103-37-7 and ‘Reaction mass of benzyl 2-(2-methoxyethoxy)ethyl adipate and bis[2-(2-methoxyethoxy)ethyl] adipate and dibenzyl adipate’ hereafter referred to as DAIFATTY-121, CAS 1175612-76-6). The Lead Registrant will aim to purchase study access for the supporting substances to include the respective RSS to this dossier.

The considerations based on the experimental data of the aforementioned substances was supported by calculations on biodegradation conducted with BioWin v.4.11 included in EPI Suite 4.11.

Experimental data on 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate':

Currenta, 2020:

In a ready biodegradability study in accordance with the Council Regulation (EC) 440/2008 Method C.4 -E “Closed Bottle Test” (2008) the biodegradability of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' was assessed. This test method is in all essential parts identical with OECD Guideline 301 D (adopted July 1992).

Within 28 days, a degradation of 62 % of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' was determined. The pass level for ready biodegradation for OECD TG 301D is 60% and was therefore met by the assessed substance within the given timeframe. However, the 10-day window criterium was not met. 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' is a mixture of three adipates (bis-benzyl, bis-alkyl and benzyl-alkyl adipate) and therefore the biodegradation of this mixture might be stepwise, resulting in the failure of the 10-day window. According to the ECHA Guidance R.7b (2017, p. 210) “the 10 day window need not be applied to a mixture of structurally similar constituents and if it is anticipated that a sequential biodegradation of the individual constituents is taking place”. Therefore, the results of this study strongly indicate a ready biodegradation of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'.

 

Kanne, 1989:

A test on ready biodegradability was conducted according to OECD Guideline 301 C (Ready Biodegradability: Modified MITI Test (I)). After 28 days, 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' showed 79 % degradation. The criterion of the 10-day window was met. 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' is considered to be "Readily Biodegradable".

Based on previously missing information (e.g. temperature and pH, missing degradation curve) ECHA did not consider this study as reliable. However, the biodegradation curve could be included in the dossier and the registrant considers this study to support the conclusion on ready biodegradability of the substance.

 

Experimental data on supporting substances:

bis(2-ethylhexyl) adipate, CAS 103-23-1 (Constituent A):

The substance bis(2-ethylhexyl) adipate is contained in the registered substance as Constituent A with up to 35 %. From the ECHA disseminated registration dossier it is evident, that the substance reached a biodegradation of 90 – 100 % in 28 days and passed the 10-day-window. Therefore, according to the OECD criteria, this Constituent A of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' is determined to be readily biodegradable.

DAIFATTY-121, CAS 1175612-76-6:

The substance DAIFATTY-121 (CAS 1175612-76-6) shows a significant similarity to 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'. Both substances consist of the three iterative constituents of the building blocks dibenzyl, adipate and an alkyl moiety, which in the case of the 2-(2-methoxyethoxy)ethyl substituent of DAIFATTY-121 includes an ether functionality. As a consequence, the constituent dibenzyl adipate (Constituent B of the registered substance) is present in both substances and the biodegradation of DAIFATTY-121 might give valuable information on the biodegradability of Constituent B of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'.

From the ECHA disseminated registration dossier of DAIFATTY-121 it can be found that the biodegradability has been assessed in an OECD TG 301C MITI biodegradation test which was assigned a reliability of 1. The multi constituent substance reached a biodegradation of 86% to 99% after 28 days and was therefore determined to be readily biodegradable.

Therefore, it can be concluded that Constituent B also present in 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate', as well as mixed adipates containing alkyl and benzyl moieties should be considered readily biodegradable.

benzylbutyrat, CAS 103-37-7:

The substance benzylbutyrat (CAS 103-37-7) might be considered in the assessment of the biodegradation of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' as an example of the structural motif of benzyl esters. This structural element is present in two of three constituents (Constituents B and C) of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'.

From the ECHA disseminated registration dossier of benzylbutyrat it can be found that the ready biodegradation was determined according the OECD TG 301F. The substance reached a biodegradation of 88% after 28 days and fulfilled the 10-day-window criterion. Therefore, it was determined to be readily biodegradable.

 

Supporting QSAR calculations:

To support the experimental data above, biodegradability of the constituents of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' and the supporting substances were calculated with BioWin v.4.11 included in EPI Suite 4.11. BioWin calculates different parameters of which the MITI probability of biodegradation (linear) and the Survey Model for ultimate biodegradation are the criteria to decide whether a substance is predicted to be readily biodegradable or not. If the ultimate survey model result is "weeks" or faster (i.e. "days", "days to weeks", or "weeks") AND MITI probability of biodegradation (linear) is >= 0.5, then the prediction is YES (readily biodegradable). If this condition is not satisfied, the prediction is NO (not readily biodegradable). This method is based on application of Bayesian analysis to ready biodegradation data.

For the Survey Model the rating was determined by biodegradation experts based on a total of 200 compounds (Boethling et al. 1994, Boethling and Sabljic 1989) by assigning a score between 1 and 5 to each substance’s biodegradability. This is a semi-quantitative prediction of the biodegradability. The rating does not correspond to half-lifes:

 

Calculated rating:	Predicted degradation time:
>4.75 - 5	Hours
<4.25 - 4.75	Hours to days
>3.75 - 4.25	Days
>3.25 - 3.75	Days to weeks
>2.75 - 3.25	Weeks
>2.25 - 2.75	Weeks to months
>1.75 - 2.25	Months
<1.75	recalcitrant

 

The results of the calculated biodegradabilities for the evaluated substances are summarized in the table below.

 

	Constituents of the registered substance
	bis(2-ethylhexyl) adipate Constituent A CAS 103-23-1	dibenzyl adipate Constituent B CAS 2451-84-5	benzyl 2-ethylhexyl adipate Constituent C CAS 58394-64-2	benzyl 2-(2-methoxyethoxy)ethyl adipate CAS 549533-43-9	bis[2-(2-methoxyethoxy)ethyl] adipate CAS 141-17-3	benzylbutyrat CAS 103-37-7
MITI probability of biodegradation (linear)	0.8212	0.6631	0.7421	0.7363	0.8300	0.625
Survey Model – ultimate biodegradation	3.26 (days – weeks)	2.80 (weeks)	3.03 (weeks)	2.74 (weeks – months)	3.08 (weeks)	2.97 (weeks)
Conclusion on biodegradation	yes	yes	yes	no	yes	yes

 

From the results of the calculations each constituent of the registered is predicted to be readily biodegradable. For Constituent A this is in conjunction with the experimental result. For Constituent B this is also in conjunction with the experimental result of the supporting substance DAIFATTY-121. The only constituent for which no experimental result is available (Constituent C) is predicted to be readily biodegradable with a MITI probability and survey model value on ultimate biodegradation between the other two constituents. The only predicted substance with ‘no’ as a final conclusion on biodegradation is one constituent of DAIFATTY-121. However, with a MITI probability of biodegradation well above 0.5 and a survey model value only slightly below an acceptable value of 2.75 (corresponding to weeks) this result does not invalidate the prediction.

 

Conclusion:

For the registered substance 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' two experimental studies on ready biodegradability are available. Both studies show, that the multi constituent substance is biodegraded under the given conditions to a degree that is above the pass level for ready biodegradability. In the more recent study (Currenta, 2020) however the 10-day-window criterium is not fulfilled. Based on the structural similarity of the constituents of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' and according to ECHA Guidance R.7b (2017, p. 210) the 10-day-window might not be applicable for 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate'. Furthermore, the registrant examined experimental biodegradation data for one constituent of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' (Constituent A) as well as closely related supporting substances that serve as representatives for alkyl and benzyl adipates. The experimental data was additionally compared with calculated biodegradation predictions (BioWin v. 4.11) for those substances.

From the discussed information it is concluded that each constituent of 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' should be regarded as readily biodegradable and therefore despite not fulfilling the 10-day-window in the most recent study (Currenta, 2020) 'Reaction mass of benzyl 2-ethylhexyl adipate and bis(2-ethylhexyl) adipate and dibenzyl adipate' should be considered readily biodegradable.