Reaction products of acrylic acid with 2,2'-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol]

Biodegradation in water and sediment: simulation tests

Administrative data

Endpoint:

biodegradation in water: simulation testing on ultimate degradation in surface water

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From16 July , 2014 to 15 September, 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method C.4-E (Determination of the "Ready" Biodegradability - Closed Bottle Test)

Deviations:

yes

Remarks:

minor: Ammonium chloride was omitted from the medium to prevent oxygen consumption due to nitrification (omission does not result in nitrogen limitation as shown by the biodegradation of the reference compound).

Qualifier:

according to guideline

Guideline:

ISO DIS 9408 (Ultimate Aerobic Biodegradability - Method by Determining the Oxygen Demand in a Closed Respirometer)

Deviations:

yes

Remarks:

minor: Ammonium chloride was omitted from the medium to prevent oxygen consumption due to nitrification (omission does not result in nitrogen limitation as shown by the biodegradation of the reference compound).

Qualifier:

according to guideline

Guideline:

OECD Guideline 301 D (Ready Biodegradability: Closed Bottle Test)

Deviations:

yes

Remarks:

minor: Ammonium chloride was omitted from the medium to prevent oxygen consumption due to nitrification (omission does not result in nitrogen limitation as shown by the biodegradation of the reference compound).

GLP compliance:

yes (incl. QA statement)

Oxygen conditions:

aerobic

Inoculum or test system:

activated sludge, domestic, non-adapted

Details on inoculum:

River water was sampled from the Rhine near Heveadorp, The Netherlands (10-07-2014). The nearest plant (Arnhem-Zuid) treating domestic waste water biologically was 3 km upstream. The river water was aerated for 7 d before use to reduce the endogenous respiration. River water without particles was used as inoculum. The particles were removed by sedimentation after 1 d while moderately aerating. The inoculum was not pre-adapted to the test substance.

Duration of test (contact time):

ca. 60 d

Initial conc.:

4 mg/L

Based on:

test mat.

Parameter followed for biodegradation estimation:

O2 consumption

Details on study design:

Test bottles
The test was performed in 0.30 L BOD (biological oxygen demand) bottles with glass stoppers.

Nutrients, stocks and administration
The river water used in the Closed Bottle test was spiked per liter of water with 8.5 mg KH2PO4, 21.75 mg K2HPO4, 33.3 mg Na2HPO4.2H2O, 22.5 mgMgSO4.7H2O, 27.5 mg CaCl2, 0.25 mg FeCl3.6H2O. Ammonium chloride was not added to the river water to prevent nitrification. Test substance was administered using a stock emulsion prepared in deionized water with polyalkoxylate alkylphenol both at a concentration of 1.0 g/L. Additional control bottles contained polyalkoxylate alkylphenol. Sodium acetate was added to the bottles using a stock solution of 1.0 g/L.

Test procedures
Use was made of 10 bottles containing only river water, 6 bottles containing river water and sodium acetate, 10 bottles containing river water with test substance and surfactant, and 10 bottles containing river water with surfactant. The concentrations of the test substance, surfactant and sodium acetate in the bottles were 4.0, 4.0 and 6.7 mg/L, respectively. The zero time bottles were immediately analyzed for dissolved oxygen using an oxygen electrode. The remaining bottles were closed and incubated in the dark. Two duplicate bottles of all series were withdrawn for analyses of the dissolved oxygen concentration at Day 7, 14, 21, and 28. The Closed bottle test was prolonged by measuring the course of the oxygen decrease in the bottles of Day 28 using a special funnel and oxygen electrode.

Reference substance:

acetic acid, sodium salt

Key result

Parameter:

% degradation (O2 consumption)

Value:

ca. 25

Sampling time:

28 d

Key result

Parameter:

% degradation (O2 consumption)

Value:

ca. 46

Sampling time:

60 d

Details on results:

Theoretical oxygen demand (ThOD)
The calculated theoretical oxygen demand (ThOD) of the main component was 1.9 mg/mg. All other components present in the test substance (information of the sponsor) do have comparable ThODs. The ThOD of sodium acetate was 0.8 mg/mg.

Toxicity
Inhibition of the degradation of a well-degradable compound, sodium acetate by the test substance in the closed bottle test was not determined because possible toxicity of test substance to microorganisms degrading acetate is not relevant. Inhibition of the endogenous respiration of the inoculum by the test substance was not detected. Therefore, no inhibition of the biodegradation due to the "high" initial concentration of the test substance is expected.

Test conditions
The pH of the media was 8.0 at the start of the test. The pH of the medium at Day 28 was 7.9 (controls) and 7.8 (test). Temperatures were within the prescribed temperature range of 22 to 24°C.

Validity of the test
The validity of the test is demonstrated by an endogenous respiration of 1.5 mg/L at Day 28. Furthermore, the differences of the replicate values at Day 28 were less than 20%. The biodegradation percentage of the reference substance, sodium acetate, at Day 14 was 83. Finally, the validity of the test was shown by oxygen concentrations >0.5 mg/L in all bottles during the test period.

Biodegradability
The test substance was biodegraded by 25% at Day 28 in the Closed Bottle test. In the prolonged Closed Bottle test this substance was biodegraded by 46% at Day 60. These results demonstrate that the test substance is inherently biodegradable.

Results with reference substance:

The biodegradation percentage of the reference substance, sodium acetate, at Day 14 was 83.

Table 1: Oxygen consumption (mg/L) and the percentages biodegradation of the test Substance (BOD/ThOD) and reference substance (BOD/ThOD) in the Closed Bottle test

Time (d)	Oxygen consumption (mg/L)		Biodegradation (%)
	Test substance	Reference substance	Test substance	Reference substance
0	0.0	0.0	0	0
7	0.3	4.2	4	78
14	0.4	4.5	5	83
21	0.8		11
28	1.8		25
42	1.8		25
60	3.5		46

Validity criteria fulfilled:

yes

Interpretation of results:

other: Not readily biodegradable, but results on Day 60 indicate inherent biodegradation potential

Conclusions:

Under the conditions of the study, the test substance is not readily biodegradable, but can be considered to be inherently biodegradable.

Executive summary:

A study was conducted to determine the inherent biodegradability of the test substance according to an extended version of OECD Guideline 301D (prolonged closed bottle test) , in compliance with GLP. The test was performed in 0.30 L BOD (biological oxygen demand) bottles with glass stoppers. There were 10 bottles containing only river water, 6 bottles containing river water and sodium acetate, 10 bottles containing river water with test substance and surfactant, and 10 bottles containing river water with surfactant. The concentrations of test substance, surfactant and sodium acetate in the bottles were 4.0, 4.0 and 6.7 mg/L, respectively. No reduction in the endogenous respiration was observed at Day 7. The test substance was therefore considered to be non-inhibitory to the inoculum. The test was valid, as shown by an endogenous respiration of 1.5 mg/L and by the total mineralization of the reference compound, sodium acetate. Sodium acetate was degraded by 83% of its theoretical oxygen demand after 14 d. Oxygen concentrations remained >0.5 mg/L in all bottles during the test period. The test substance was biodegraded by 25% at Day 28 and by 46% at Day 60. Under the conditions of the study, the test substance can therefore be considered inherently biodegradable (Ginkel, 2014).

Cross-reference 2

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Water solubility was determined according to OECD Guideline 105 (Jeuniaux, 2012) as well as using QSAR models from EPISuite v.4.11 (US EPA, 2018).

Water solubility:

2 655 mg/L

at the temperature of:

25 °C

Experimental value for di-TMPTTA (major constituent):15 mg/L at 25°C 

Predicted values (EPI Suite v.4.11):

WSKOWWIN v.1.43: Water solubility (WS) range: 1.52E-12 to 3142 mg/L at 25°C; weighted average: 63 mg/L at 25°C.

WATERNT v.1.02: WS range:1.29E-06 to 2.82E+05 mg/L at25°C; weighted average: 5246 mg/Lat 25°C

The test substance is overall considered to be of low water solubility as evidenced from the experimentally determined water solubility value for the major constituent as well as the ecotox studies (leading to handling the test concentrations as WAFs).

However, in the absence of experimental WS data for all constituents, predicted values were generated to get an idea about the potential WS differences across the different constituents. Based on the predictions, the range of WS values were too wide and the highest values corresponded to two constituents: di-TMPMA and di-TMPDA, both of which are present at very low concentrations (i.e., <5% typical concentrations); therefore these values, even though represent worst case have not been taken forward for risk assessment. Instead the weighted average values, has been considered further for hazard as well as risk assessment.

The respective weighted average water solubility values for the test substance using WSKOWWIN and WATERNT was calculated as 63 mg/L and 5246 mg/L (US EPA, 2018). A mean weighted average value based on both the QSAR models was calculated as 2655 mg/L 25°C.

Cross-reference 3

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Based on the available weight of evidence i.e., experimental log Kow values of the major constituents, predicted BCF values of the constituents (combined with high MW and Dmax values for the out of domain constituents), together with the absence of systemic effects in repeated dose study in mammals, overall indicate a low bioaccumulation potential for the test substance. As a conservative approach, the higher weighted average BCF value from EPISuite has been considered further for risk assessment.

BCF (aquatic species):

9.38 L/kg ww

The test substance is an UVCB with severalconstituents, varying mainly in the number of acrylates attached totrimethylolpropane(TMP) backbone as well as adducts formation.The experimental log Kow values for the major constituents of the test substance were determined to be 4.14 and 3.05 (respectively representing 81% and 10% of total base peak area) and were between -0.10 and 3.8 for the minor constituents (representing together <10% peak area). Based on this information, the test substance cannot be considered B or vB as it is below the log Kow ≤ 4.5 threshold, according to the REACH criteria.

This is further supported by the QSAR based BCF predictions for individual constituents using BCF base-line (LMC) and Arnot Gobas model of BCFBAF (EPISuite):

The bioaccumulation factor (BCF) of the test substance was predicted using the BCF base line model v.05.12 program of LMC. Since the test substance is a UVCB with similar constituents (varying mainly in the number of acrylates TMP backbone as well as adduct formation) log BCF values were predicted for the individual constituents followed by the determination of an overall weighted-average value using mole fractions. SMILES codes were used as the input parameter. The predicted log BCF of the individual constituents ranged from 0.61 to 0.88, leading to a weighted average log BCF value of 0.78 (i.e., BCF = 6.03 L/Kg wet-wt for the test substance (LMC, 2018). Based on the BCF predictions, the test substance can be considered to have a low bioaccumulation potential.

The bioaccumulation factor (BCF) of the test substance was predicted using the BCFBAF v.3.01 program (EPISuite v4.11). Since the test substance is a UVCB with similar constituents (varying mainly in the number of acrylates TMP backbone as well as adduct formation) BCF values were predicted for the individual constituents followed by the determination of an overall weighted-average value based on mole fractions. SMILES codes were used as the input parameter. Using the Arnot Gobas method,which uses mitigating factors (e.g., growth dilution and metabolic biotransformations), the upper trophic BCF value for the constituents was predicted to range from 0.9 to 12.59 L/kg, leading to a weighted average BCF value of 9.38 L/kg (log BCF: 0.97) for the test substance (US EPA, 2018). With regard to the domain evaluations for both the QSAR models, most of the constituents meet the respective domain criteria, i.e., log Kow and molecular weight (MW) cut offs as defined in the BCFBAF user guide of EPISuite and general properties (log Kow, WS and MW), structural and mechanistic criteria as defined in the BCF base-line QSAR model. Only, the trimers (present at <15% of composition) due to their higher MW exceed the maximum MW of the training set (1100 g/mol). However, these constituents in general can be expected to have low permeability across membranes, considering their big size, high MW and predicted log Kow >10 (refer to Annex 5), all of which support a low bioaccumulation potential in accordance with the ECHA Guidance Chapter R.11. Therefore, the QSAR predictions from the two models can be considered to be reliable with low degree of uncertainty.

Overall, based on the available weight of evidence i.e., experimental log Kow values of the major constituents, predicted BCF values of the constituents (combined with high MW and Dmax values for the out of domain constituents), together with the absence of systemic effects in repeated dose study in mammals, overall indicate a low bioaccumulation potential for the test substance. As a conservative approach, the higher weighted average BCF value from EPISuite has been considered further for risk assessment.

Cross-reference 4

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Assessed substance:

substance itself

Composition of assessed substance:

Reaction products of acrylic acid with 2,2’-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol] (legal entity composition)

Reaction products of acrylic acid with 2,2’-[oxybis(methylene)]bis[2-ethylpropane-1,3-diol] (boundary composition)

PBT status of the assessed substance:

the substance is not PBT / vPvB

Remark:

The test substance was found to be not readily biodegradable in the modified Sturm test as well as closed bottle tests. However, extension of the close bottle test up to Day 60 resulted in 46% degradation, indicating an inherent biodegradation potential of the test substance. Therefore, the test substance can be considered to be potentially persistent (P) but not very persistent (vP) according to the REACH criteria.

This is further supported by the primary half-life QSAR predictions for the different constituents ranging from <1 day to 6.51 days using CATALOGIC 301C and CATALOGIC Kinetic 301F models, which are well below the P or vP criteria of 40 and 60 days according to Section 1 of Annex XIII to the REACH Regulation.
Further, the primary half-life values of 12 degradation products of the test substance identified and predicted using CATALOGIC 301C v.12.17 model, indicated that except for two products, the half-life values of the majority of the degradation products were less than 40 days (see Annex 7 for further details).
Therefore, the test substance can be overall considered to be not persistent in the environment, except for the two degradation products.

Conclusion on P / vP properties:

No conclusion can be reached based on available information

Remark:

Potentially P

Not B and not vB based on: Log Kow ≤ 4.5

Remark:

The test substance is a multi-constituent product. For the major constituents, log Kow values were 4.14 and 3.05 (respectively 81% and 10% of total base peak area). For the minor constituents, log Kow values were between -0.10 and 3.8. Based on this information, it does not qualify as bioaccumulative according to the REACH criteria.
Further, the predicted log kow values of 12 degradation products of the test substance identified using CATALOGIC 301C v.12.17 model, indicated that none of the degradation products exceeded the cut-off of 4.5, suggesting they are not bioaccumulative according to the REACH criteria (see Annex 7 for further details).

Remark:

The range of predicted BCF values for the different constituents of the test substance using the Arnot Gobas model in BCFBAF v3.02 program of EPI SuiteTM v 4.11 (0.9 to 12.59 L/kg ww) and the BCF baseline model v.05.12 program of LMC (4.07 to 7.59 L/kg ww) suggests that the test substance is not considered to bioaccumulative.
This is because the BCF values are well below the cut-off value of 5,000 L/kg for “very bioaccumulative” (vB) and 2,000 L/kg for “bioaccumulative” (B) as per PBT and vPvB criteria as set out in the REACH Technical Guidance Document Chapter R.11 (Table R.11—1) as well as in Section 1 of Annex XIII to the REACH Regulation.

Remark:

The absence of toxicologically significant systemic toxicity up to highest tested dose in the mammalian repeated dose toxicity studies (OECD 422 and OECD 408) with the test substance, supports a low bioaccumulation potential.

Terrestrial bioaccumulation: The low vapour pressure value of the test substance suggests a low exposure potential of the terrestrial organisms via air. In an unlikely case of exposure, the experimental log Kow or the predicted BCF values for the test substance suggests a low bioaccumulation potential. This is supported by the absence of toxicologically significant toxicity up to highest tested dose in a mammalian repeated dose toxicity studies (OECD 422 and OECD 408) with the test substance. Based on all the above weight of evidence information, the terrestrial bioaccumulation potential of the test substance is also expected to be low.

Conclusion on B / vB properties:

not B/vB

Not T based on:

EC10 or NOEC ≥ 0.01 mg/L for marine / freshwater organisms (long-term toxicity):

The long-term equivalent 72h ErC10 value from the algae study was determined to be 0.51 mg/L (measured; TWA). This value is higher than the 0.01 mg/L limit specified as per the PBT and vPvB criteria, as set out in the REACH technical guidance document Chapter R.11 (Table R.11—1) as well as in Section 1 of Annex XIII to the REACH Regulation. This indicates the test substance is not toxic (not T).

and substance is not classified as carcinogenic (category 1 or 2), mutagenic (category 1 or 2), or toxic for reproduction (category 1, 2 or 3) according to Directive 67/548/EEC or carcinogenic (category 1A or 1B), germ cell mutagenic (category 1A or 1B), or toxic for reproduction (category 1A, 1B or 2) according to Regulation EC No 1272/2008:

The test substance is not classified for the above endpoints.

and no other evidence of chronic toxicity, as identified by the classifications T, R48 or Xn, R48 according to Directive 67/548/EEC or specific target organ toxicity after repeated exposure (STOT RE category 1 or 2) according to Regulation EC No 1272/2008:

The test substance did not exhibit critical a systemic toxic effects in the screening study, hence is not classified as STOT RE.

Remark:

Short-term fish, aquatic invertebrates and algae toxicity studies are available on the test substance. Based on these studies, fish has been identified to be the most sensitive species with the lowest 96 h LC50 value determined to be at 1.2 mg/L (measured; TWA) which is above the limit of 0.01 mg/L specified as per the PBT and vPvB screening criteria as set out in the REACH technical guidance document Chapter R.11 (Table R.11—2) as well as in Section 3.1 of Annex XIII to the REACH Regulation. This indicates the test substance is not toxic (not T).

Further, the predicted L(E)C50 values of 12 degradation products of the test substance identified using ECOSAR v.2.2, indicated that none of the degradation products exceeded the limit of 0.01 mg/L, suggesting they are not toxic according to the REACH criteria (see Annex 7 for further details).

Conclusion on T properties:

not T

Results and discussion

Transformation products:

not specified