Reactionmass of octan-2-yl prop-2-enoate and octan-3-yl prop-2-enoate and octan-4-yl prop-2-enoate

Hydrolysis

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

disregarded due to major methodological deficiencies

Study period:

December 09, 2019 to March 20, 2020

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Source and lot/batch No.of test material: 3M FMRD, S352546
- Expiration date of the lot/batch: August 12, 2021
- Purity test date:August 12, 2019
- Storage condisition: 15 -25 °C

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Sampling intervals for the parent/transformation products:
Tier 1 preliminary test: 25.0 mL of buffer solution at pH 4, 7 and 9 spiked with 124 µL of 1008.4 mg/L MTDID 44428 stock solution was vortexed for about 30 seconds to generate a test solution of 5 mg/L in glass vessel (total volume about 45 mL). Then this solution was transferred to another glass vessel (total volume about 23 mL) to the top with aluminum foil lined Teflon caps. The test vessels were uprightly placed in a constant incubator at 50±0.5˚C in dark. The initial concentration of test item was analyzed immediately after preparation in triplicates, the concentration on the 5th day was also analyzed in triplicates. A test vial washing by 5.0mL acetonitrile was also collected separately and analyzed.

Tier 2: tier 2 hydrolysis was conducted at the pH conditions that the test item was unstabl: 25.0 mL buffer solution at pH 4.0, 7.0 and 9.0 spiked with 124µL of 1008.4 mg/L MTDID 44428 stock solution was vortexed for about 30 seconds to generate a test solution of 5 mg/L in glass vessel (total volume about 45 mL). Then this solution was transferred to another glass vessel (total volume about 23 mL) to the top with aluminum foil lined Teflon caps. Total of 29 replicates were prepared for each temperature, but Time 0 was prepared in five replicates. Then the vessels were uprightly placed in a constant incubator at 15±0.5˚C, 25±0.5˚C and 50±0.5˚C in dark. The concentration was measured on the 0, 6h, 1d, 2d, 3d, 4d, and in triplicates on each sampling point at 50±0.5˚C. While only 0, 6h, 2d , 5d was sampled and analyzed at 15±0.5˚C and 25±0.5˚C.

Tier 3: identification of major hydrolysis products: 25.0 mL buffer solution at pH 4.0, 7.0 and 9.0 spiked with 124µL of MTDID 44428 stock solution was vortexed for about 30 seconds to generate an test solution of 5 mg/L in glass vessel (total volume about 45 mL). This solution was transferred to another glass vessel (total volume about 23 mL) to the top with aluminum foil lined Teflon caps. The test vessels were uprightly placed in a constant incubator at 50±0.5˚C in dark. The initial concentration of test item was analyzed immediately after preparation in duplicates. 2-octanol, 3-octanol and 4-octanol were proposed to be the major hydrolysis products. The retention time and qualitative ion between proposed hydrolysis products and commercial standard references was compared.

- Sampling method for parent compound: 10.0 mL solution was transferred into a 40 mL vial to which 0.5 mL EDTA of 0.1 mol/L was added, followed by vortex for about 5 seconds. Then 10.0 mL CH2Cl2 was added to extract test item by vortex for about 1 min. After extracting, the solution stayed overnight at room temperature for equilibrium. The CH2Cl2 layer was filtered by 0.22μm membrane, and then 50μL of which was added into a vial of autosampler followed by adding 950μL CH2Cl2 solvent. After vortex, the diluted solution was analyzed by GC-MS/MS.

- Sampling method for hydrolysis products: 5.0mL of residual solution in one test vessel harvested on each timepoint was transferred into another vial, and then 5.0 mL ethyl acetate (in a 1:1 volume ratio to the buffer solution) was added to extract by vortex for 1 min. After extracting, the solution was stayed overnight for equilibrium. The ethyl acetate layer was filtered by 0.22μm membrane prior to being determined by GC-MS/MS.

- Sampling methods for the volatile compounds, if any: None
- Sampling intervals/times for pH measurements: None
- Sampling intervals/times for sterility check: None.
- Sample storage conditions before analysis: 2-8 °C
- Other observation, if any (e.g.: precipitation, color change etc.): None

Buffers:

- pH: 4, 7, 9
- Type and final molarity of buffer:
pH 4: 500 mL of 0.1 mol/L potassium dihydrogen citrate + 90 mL 0.1 mol/L NaOH, bring to 1000 mL by pure water.
pH 7: 500 mL of 0.1 mol/L KH2PO4 + 296 mL of 0.1 mol/L NaOH, bring to 1000 mL by pure water.
pH 9: 500 mL of 0.1 mol/L boric acid in 0.1 mol/L KCl + 213 mL of 0.1 mol/L NaOH, bring to 1000 mL by pure water.
All the buffer solutions and glass vessels used in this study were sterilized beforehand under 121°C for 30 min.
- Composition of buffer:

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1.293 mg/L

Remarks:

Tier 1 test for 2-octyl acrylate, average initial conc of 1.1962 mg/L at pH 4, and average initial conc of 1.4766 mg/L at pH 9.

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1.066 mg/L

Remarks:

Tier 1 test for 3-octyl acrylate, average initial conc of 1.0019 mg/L at pH 4, and average initial conc of 1.1900 mg/L at pH 9.

Duration:

5 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.815 mg/L

Remarks:

Tier 1 test for 4-octyl acrylate, average initial concentration of 0.7610 mg/L at pH 4, average initial concentration of 0.9014 mg/L at pH 9

Duration:

4 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1.655 mg/L

Remarks:

Tier 2 test for 2-octyl acrylate, average initial conc of 1.6508 mg/L at pH 4, and average initial conc of 1.4514 mg/L at pH 9.

Duration:

4 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1.446 mg/L

Remarks:

Tier 2 test for 3-octyl acrylate, average initial conc of 1.4493 mg/L at pH 4, and average initial conc of 1.1849 mg/L at pH 9.

Duration:

4 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

1.1 mg/L

Remarks:

Tier 2 test for 4-octyl acrylate, average initial conc of 1.2822 mg/L at pH 4, and average initial conc of 1.0122 mg/L at pH 9.

Number of replicates:

Tier 1 study: Triplcate
Tier 2 study: For 15 °C and 25 °C, triplicate samples were analyzed for time 0, duplicate samples were analyzed for 6-hour sampling time. For 50 °C, 5 replicates samples were analyzed for time 0, triplicate samples were analyzed for 4 day sampling time.

Positive controls:

no

Negative controls:

no

Preliminary study:

For tier 1 study, hydrolysis of the MTDID 44428 was evaluated at pH 4, 7 and 9 and incubated in constant temperature of 50±0.5˚C in dark for 5 days, under static conditions. The initial concentration in the buffer solution was prepared at 5 mg/L MTDID 44428. The measured concentration for 2-octyl acrylate isomer at time 0 were 1.1962 mg/L, 1.2932 mg/L and 1.4766 mg/L for pH 4, 7, and 9 respectively. The measured concentration for 3-octyl acrylate isomer at time 0 were 1.0019 mg/L, 1.0661 mg/L and 1.1900 mg/L for pH 4, 7, and 9 respectively. The measured concentration for 4-octyl acrylate isomer at time 0 were 0.7610 mg/L, 0.8151 mg/L and 0.9014 mg/L for pH 4, 7, and 9 respectively.
The measured concentration for 2-octyl acrylate isomer at day 5 were 0.0723 mg/L, 0.0797 mg/L and < LOD (0.001945 mg/L) for pH 4, 7, and 9 respectively. The measured concentration for 3-octyl acrylate isomer at day 5 were 0.0374 mg/L, 0.0856 mg/L and < LOD (0.00171 mg/L) for pH 4, 7, and 9 respectively. The measured concentration for 4-octyl acrylate isomer at day 5 were all < LOD (0.00133 mg/L) for pH 4, 7, and 9.

After 5 days, all isomers had % loss of > 90% (Table 1). A tier 2 study needs to be conducted.

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

Details on hydrolysis and appearance of transformation product(s):

- Formation and decline of each transformation product during test: Hydrolytic degradation of MTDID44428 to the corresponding alcohols.
- Pathways for transformation:
- Other:

Remarks on result:

not determinable because of methodological limitations

Details on results:

Tier 2 hydrolysis study results were reported for a period of 4 days with 6 sampling points for 50 °C. However, results for 25 °C and 15 °C were only reported for time 0 and hour 6 sampling points.

For hydrolysis study at 50 °C: the loss of test item was fast within 6-hour, independent of pH condition. The loss percentage were 85% - 93.5% for all isomers (Table 3). For hydrolysis study at 25 °C (Table 2) : the loss of test item over 6-hour sampling time were 59 % - 71.3% for 2-octyl acrylate isomer, 79.6 % - 88.2% for 3-octyl acrylate isomer, and 80.3 % - 92.2% for 4-octyl acrylate isomer. For hydrolysis study at 15 °C (Table 2): the loss of test item over 6-hour sampling time were 9.6 % - 54.1% for 2-octyl acrylate isomer, 20 % - 54.4% for 3-octyl acrylate isomer, and 17.9 % - 54.1% for 4-octyl acrylate isomer. Because there were not enough sampling points at all conditions, a loss curve cannot be developed. No half-life was calculated.

Hydrolysis samples were analyzed for the predicted hydrolysis products:2-octyl alcohol, 3-octyl alcohol, and 4-octyl alcohol. The predicted hydrolysis products were exacted with ethyl acetate and measured by GC/MS/MS. The calibration curve for the three proposed 2-octyl alcohol, 3-octyl alcohol, and 4-octyl alcohol were not able to be developed, even though valid analysis methods has been established. Therefore, quantitation of the hydrolysis cannot be made. The instrument response signal for the proposed hydrolysis products were present in the time 0 samples, whereas the response signal from 6 hours samples and 1 day samples were close to the response signal of the time 0 samples. It cannot draw conclusion that the proposed hydrolysis products were generated during the study time frame. In other words, the loss of the parent test item due to hydrolysis cannot be confirmed in the present study.

Table 1. Tier 1 study results⁽¹⁾

 

pH	Temp (°C)	Elapsed Time (Days)	Avg. conc. at TP 0 (ng/mL) (RSD%)	Avg. conc. at end time point (ng/mL) (RSD%)	% Loss at end time point
2-octyl acrylate
4	50	0 - 5	1.1962	0.0723	>94.0
7	50	0 - 5	1.2932	0.0797	>93.8
9	50	0 - 5	1.4766	<LOD	>99.9
3-octyl acrylate
4	50	0 - 5	1.0019	0.0374	>96.3
7	50	0 - 5	1.0661	0.0856	>92.0
9	50	0 - 5	1.1900	<LOD	>99.9
4-octyl acrylate
4	50	0 - 5	0.7610	<LOD	>92.2
7	50	0 - 5	0.8151	<LOD	>99.8
9	50	0 - 5	0.9014	<LOD	>99.9

 

(1) LOD values are 0.001945 mg/L for2-octyl acrylate,0.00171 mg/L for3-octyl acrylate, and0.00133 mg/L for4-octyl acrylate.

Table 2. Measured concentration of MTDID 44428 in Tier 2 study over 6 hours

 

pH	Temp (°C)	Elapsed Time	Avg. conc. at TP 0 (mg/L)^(1)	Avg. conc. at end time point (mg/L)^(1)	% loss of parent
2-octyl acrylate
4	15	0 – 6 hours	1.1108	0.6869	38.2
4	25	0 – 6 hours	1.1108	0.4470	59.8
4	50	0 – 6 hours	1.6508	0.1701	89.7
7	15	0 – 6 hours	1.0229	0.9249	9.6
7	25	0 – 6 hours	1.0229	0.4158	59.3
7	50	0 – 6 hours	1.6548	0.1072	93.5
9	15	0 – 6 hours	1.4321	0.6580	54.1
9	25	0 – 6 hours	1.4321	0.4105	71.3
9	50	0 – 6 hours	1.4514	0.1561	89.2
3-octyl acrylate
4	15	0 – 6 hours	1.2440	0.5671	54.4
4	25	0 – 6 hours	1.2440	0.1660	86.7
4	50	0 – 6 hours	1.4493	0.1707	88.2
7	15	0 – 6 hours	1.0673	0.8522	20.0
7	25	0 – 6 hours	1.0673	0.2175	79.6
7	50	0 – 6 hours	1.4456	0.1168	93.5
9	15	0 – 6 hours	1.5115	0.6558	38.6
9	25	0 – 6 hours	1.5115	0.1264	88.2
9	50	0 – 6 hours	1.1849	0.1783	85.0
4-octyl acrylate
4	15	0 – 6 hours	1.0084	0.4830	52.1
4	25	0 – 6 hours	1.0084	0.1560	84.5
4	50	0 – 6 hours	1.2822	0.1338	89.6
7	15	0 – 6 hours	0.8493	0.6977	17.9
7	25	0 – 6 hours	0.8493	0.1673	80.3
7	50	0 – 6 hours	1.1003	0.1042	90.5
9	15	0 – 6 hours	1.1336	0.5206	54.1
9	25	0 – 6 hours	1.1336	0.0887	92.2
9	50	0 – 6 hours	1.0122	0.1486	85.3

(1)     For 15 °C and  25 °C, triplicate samples were analyzed for time 0, duplicate samples were analyzed for 6-hour sampling time.

For 50 °C, 5 replicates samples were analyzed for time 0, triplicate samples were analyzed for rest sampling times

Table 3. Measured concentration of MTDID 44428 in Tier 2 study at 50 °C

 

pH	Sample interval (days)	Avg. conc. (mg/L)^(1)	% loss of parent	Avg. conc. (mg/L)^(1)	% loss of parent	Avg. conc. (mg/L)^(1)	% loss of parent
		2-octyl acrylate	2-octyl acrylate	3-octyl acrylate	3-octyl acrylate	4-octyl acrylate	4-octyl acrylate
4	0	1.6508	--	1.4493	--	1.2822	--
4	0.25	0.1701	89.7	0.1707	88.2	0.1338	89.6
4	1	0.1901	88.4	0.1610	88.9	0.1365	89.4
4	2	0.0802	95.1	0.0800	94.5	0.0621	95.2
4	3	0.1023	93.8	0.0980	93.2	0.0714	94.4
4	4	0.0394	97.6	0.0361	97.5	0.0271	97.9
7	0	1.6548	--	1.4456	--	1.1003	--
7	0.25	0.1072	93.5	0.1168	91.9	0.1042	90.5
7	1	0.1903	88.5	0.1790	87.6	0.1378	87.5
7	2	0.1127	93.2	0.1134	92.2	0.0927	91.6
7	3	0.0940	94.3	0.1054	92.7	0.0798	92.7
7	4	0.0987	94.0	0.0942	93.5	0.0788	92.8
9	0	1.4514	--	1.1849	--	1.0122	--
9	0.25	0.1561	89.2	0.1783	85.0	0.1486	85.3
9	1	0.0724	95.0	0.0917	92.3	0.0650	93.6
9	2	0.0676	95.3	0.0959	91.9	0.0637	93.7
9	3	0.0674	95.4	0.0794	93.3	0.0622	93.9
9	4	0.0825	94.3	0.0839	92.9	0.0710	93.0

 (1)    5 replicates samples were analyzed for time 0, triplicate samples were analyzed for rest of sampling time

Conclusions:

MTDID 44428 lost quickly in water at pH 4, 7, and 9 and temperature 15 °C, 25 °C and 50 °C. However, no half-life was calculated due to not enough sampling points at all conditions.

Executive summary:

Hydrolysis study for MTDID 44428 was performed according to OECD Guidelines No.111: Hydrolysis as a function of pH.

MTDID 44428 is a mixture of isomers. Three main isomers, 2-octyl acrylate isomer, 3-octyl acrylate isomer, and 4-octyl acrylate isomer were analyzed throughout the hydrolysis study. In a tier 1 study, test solutions containing 5 mg/L of MTDID 44428 were prepared in triplicates at each pH 4, 7 and 9 and incubated in constant temperature of 50±0.5˚C in dark for 5 days, under static conditions. After 5 days, all isomers had % loss of > 90%. A tier 2 study needs to be conducted.

Tier 2 hydrolysis study were conducted at pH 4, 7, and 9 and at 15 °C, 25 °C and 50 °C. Results were reported for a period of 4 days with 6 sampling points for 50 °C. However, results for 25 °C and 15 °C were only reported from time 0 and 6-hour sampling points. For hydrolysis study at 50 °C, the percentage loss of MTDID44428 were 85% - 93.5% for all isomers over the period of 6 hours, independent of pH condition. For hydrolysis study at 25 °C, the percentage loss of MTDID44428 were 59% -92.2% for all isomers over the period of 6 hours. For hydrolysis study at 15 °C, the percentage loss of MTDID44428 were 9.6% -54.4% for all isomers over the 6 -hours sampling point.  Because there were not enough sampling points at all conditions, a loss curve cannot be developed. No half-life was calculated.

The predicted hydrolysis products, 2-octyl alcohol, 3-octyl alcohol, and 4-octyl alcohol were exacted and analyzed by GC/MS/MS. However, quantitation of the hydrolysis products cannot be made due to the study was not able to develop calibration curves for the three proposed hydrolysis products, even though valid analysis methods has been established. Consequently, the loss of the parent test item due to hydrolysis cannot be confirmed in the present study.

Although this is a guideline study conducted under GLP compliance, the test had significant methodological deficiencies. This study is considered not reliable and a disregarded study.

Reference 2

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February 17, 2021 - April 22, 2021

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Source and lot/batch No.of test material: 41-4205-7138-6 (R-57318), CPDC Load ID S352546
- Expiration date of the lot/batch: 8/12/2024

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

- Sampling intervals for the parent/transformation products: The test vessels were prepared to perform the Tier II and Tier III determination of the hydrolysis as a function of pH using purchased certified buffers (pH 4, 7, and 9) and three temperatures (15°C, 25°C, and 50°C). A Tier I preliminary test at 50°C for five days was not performed as it was preliminarily determined that at least one isomer will hydrolyze greater than 10% within that time frame.

The tier II test was run at pH 4.0, pH 7.0 and pH 9.0 at 15 °C, 25 °C and 50 °C, respectively. The test was prepared in duplicate for each pH, each temperature and each time points. For pH 4 and pH 7: time elapsed 61.01 days and 8 time points. For pH 9: time elapsed 50 days and 8 time points for 15 °C and 25°C, 10 time points for 50 °C.

- Sampling method: Test system vials were 20-mL amber VOA vial. Buffer solutions at pH 4, 7, and 9 were purchased certified buffers solutions. Prior to dosing with test substance, the purchased buffers were sterilized, and the pH of the buffer system was confirmed using pH test strips. The buffer solutions were transferred to the test vials to zero headspace (24.5 mL). Each vial contains 5 µg/mL of MTDID 44428 by adding 25.0 µL of spiking solution of 4900 µg/mL MTDID 44428 to the open vial. Each vial was then capped and placed in an incubator shaker (temperature setting of 15, 25, or 50°C and shaker setting of 100 rpm). Each designated time point for each temperature/pH conditions was prepared in duplicate. At each sampling time, the test system vials were removed from the incubator/shaker and an aliquot (0.3 mL, 5 mL) was transferred into a 40 mL amber VOA vial containing Milli Q Water treated with a 1:1 concentrated HCl:water solution (final volume 40.5 mL). Day 0 samples were spiked directly with MTDID 44428 and extracted/diluted immediately to demonstrate the reliability of the extraction/dilution process for the test substance. Samples were analyzed by Purge and Trap GC/MS.

- Sampling methods for the volatile compounds, if any: None
- Sampling intervals/times for pH measurements: None
- Sampling intervals/times for sterility check: None. All buffers used were sterilized prior to use and the test system vessels and the pipets used to transfer the buffers were from unopened containers.
- Sample storage conditions before analysis:
- Other observation, if any (e.g.: precipitation, color change etc.):None

Buffers:

- pH: 4, 7, 9
- Type and final molarity of buffer:
pH 4: Potassium Hydrogen Phthalate Buffer (KHP)
pH 7: Potassium Phosphate (Monobasic) Buffer (KH2PO4)
pH 9: Boric Acid Buffer (H3BO3)

Buffers were sterilized via filtration through a pre-sterilized Thermo Scientific™ Nalgene™ Rapid-Flow™ 75mm filter unit. Vacuum was applied to the filtration vessel’s headspace for a minimum of three minutes to help remove any residual dissolved oxygen from the aqueous media. Prior to dosing, the pH of the buffer system was confirmed using pH test strips.

Duration:

61 d

pH:

4

Temp.:

15 °C

Initial conc. measured:

5 mg/L

Duration:

61 d

pH:

4

Temp.:

25 °C

Initial conc. measured:

5 mg/L

Duration:

61 d

pH:

4

Temp.:

50 °C

Initial conc. measured:

5 mg/L

Duration:

61 d

pH:

7

Temp.:

15 °C

Initial conc. measured:

5 mg/L

Duration:

61 d

pH:

7

Temp.:

25 °C

Initial conc. measured:

5 mg/L

Duration:

61 d

pH:

7

Temp.:

50 °C

Initial conc. measured:

5 mg/L

Duration:

50 d

pH:

9

Temp.:

15 °C

Initial conc. measured:

5 mg/L

Duration:

50 d

pH:

9

Temp.:

25 °C

Initial conc. measured:

5 mg/L

Duration:

50 d

pH:

9

Temp.:

50 °C

Initial conc. measured:

5 mg/L

Number of replicates:

2

Transformation products:

yes

No.:

#1

No.:

#2

No.:

#3

Details on hydrolysis and appearance of transformation product(s):

- Formation and decline of each transformation product during test: Hydrolytic degradation of MTDID44428 to the corresponding alcohols.
- Pathways for transformation: see Figure 1
- Other:

Key result

pH:

4

Temp.:

25 °C

Hydrolysis rate constant:

0.005 d-1

DT50:

152 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Extrapolated Half-Life for 2-octyl acrylate, 95% confidence interval: 98.2 - 339 days

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.005 d-1

DT50:

137 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Extrapolated Half-Life for 2-octyl acrylate, 95% confidence interval: 84 - 368 days

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.018 d-1

DT50:

37.7 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Extrapolated Half-Life for 2-octyl acrylate, 95% confidence interval: 32.2 - 45.4 days

Key result

pH:

7

Temp.:

25 °C

Hydrolysis rate constant:

0.003 d-1

DT50:

221 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Extrapolated Half-Life for 3-octyl acrylate, 95% confidence interval: 141- 512 days

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.007 d-1

DT50:

93.4 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Extrapolated Half-Life for 3-octyl acrylate, 95% confidence interval: 68.3 - 147 days

Key result

pH:

9

Temp.:

25 °C

Hydrolysis rate constant:

0.006 d-1

DT50:

116 d

Type:

(pseudo-)first order (= half-life)

Remarks on result:

other: Extrapolated Half-Life for 4-octyl acrylate, 95% confidence interval: 79.2 - 218 days

Other kinetic parameters:

Assuming hydrolysis followed pseudo first-order reaction kinetics.

The Half life (DT50) was calculated as:
Ln Ct = -kt + LnC0
DT50 = ln2/k

Where:
Ct: the concentration at time t (mg/L);
C0:the concentration at time 0 (mg/L);
DT50:hydrolysis half-lives (day);
k:hydrolysis rate coefficient.

Hydrolysis rate constants can then be calculated at other temperatures using the Arrhenius equation:
ln k = -E/RT + ln A
where:
k = observed rate constant (days -1), measured at different temperatures
E = activation energy (kJ/mol -1)
T = absolute temperature (K)
R = gas constant (8.314 x 10 -3 kJ/mol*K)
A = Pre-Exponential Factor (day -1)

Details on results:

Tier 2 and tier 3 studies were conducted over a period of 61 days (8 time points) for pH 4 and pH 7, and 50 days (10 time points) for pH 9 at 15 °C, 25 °C and 50 °C. Concentration of MTDID 44428 isomers and corresponding alcohol were measured for each time points, pH and temperature combination (Table 1). The recovery of each isomer of MTDID 44428 was determined for each timepoint along with the mass balance with the associated alcohol (Table 1). A timepoint was not included in the calculation of the rate constant and half-life if: 1) The test substance isomers which were not consistently less than 90% recovery over the duration of the study for a specific test condition. 2) the upper 95% confidence interval had a positive slope. A positive slope indicates possible evidence of no measurable hydrolytic activity.

For each pH and temperature combination, the hydrolytic rate constant, k, and hydrolytic half-life, DT50, were determined by plotting the natural logarithm of the measured concentrations of the parent isomers as a function of elapsed time, and performing linear regression, assuming that the hydrolysis followed pseudo first-order reaction kinetics (Table 2). The slope of the resulting linear regression provided the rate constant k in units of days-1. The 95% confidence limits of each half-life were determined by multiplying the standard error of the slope by the student’s t-test value corresponding to N-2, where N = the number of measurements used to determine the regression. The slope was then used to calculate the half-life as indicated above to provide the uncertainty. Additionally, the 95% confidence limits were also determined for the intercept to visually plot the associated linear regression.

In general, hydrolytic activity appears to increase with increased temperature, increased pH, and increased linearity of the isomers.

Although mass balance was not within 90% to 110%, overall mass balance were 78.6 -100 % at pH 9 at all temperatures for each isomer, confirming the formation of the corresponding alcohol making up the loss of the test substance. Mass balance for pH 4 and pH 7 dropped as the concentration of the test substance decreased. Formation of the corresponding alcohols was only observed at 50°C for pH 7, with mass balance of 36.1 - 67%, which was not enough to raise the mass balance to levels similar to pH 9. This suggests that there may be another non-hydrolytic process or an unaccounted for intermediate or end point with the proposed hydrolysis pathway as described in Figure 1.

Whenever a hydrolysis half-life was calculated for the parent isomer, a plot of natural logarithm of the measured concentrations for the corresponding alcohols as a function of elapsed time, was also generated in the study report.

Arrhenius constants were calculated when at least two temperatures had hydrolytic half-lives calculated at a specific pH (Table 3). Only one isomer (2-octyl acrylate) at one pH (9) had three different temperatures with hydrolytic half-lives calculated and one of the three half-lives is extrapolated. All other Arrhenius constants, if calculated, only had two different temperatures and at least one of the temperatures was an extrapolated half-life. A two-point linear regression has zero degrees of freedom which prevents the calculation of any confidence intervals. Additionally, extrapolated half-lives add to the uncertainty of the data.

Table 1. Summary of measured concentration of MTDID 44428 and transformation products⁽¹⁾

 

pH	Temp (°C)	Elapsed Time (Days)	Avg. conc. at TP 0 (ng/mL) (RPD%)	Avg. conc. at end time point (ng/mL) (RPD%)	% Avg. Recovery at end time point	Avg. conc. at TP 0 (ng/mL) (RPD%)	Avg. conc. at end time point (ng/mL) (RPD%)	Mass balance at TP 0 (%)	Mass balance at end time point (%)
			2-octyl acrylate	2-octyl acrylate	2-octyl acrylate	2-octanol	2-octanol	2-octanol	2-octanol
4	15	0 - 61	2060 (2.9%)	1490 (11%)	75.8%	45.4 (3.3%)	18.2 (4.4%)	108	77.0
4	25	0 - 61	2060 (2.9%)	1320 (9.1%)	67.3%	45.4 (3.3%)	18.0 (3.3%)	108	68.5
4	50	0 - 61	2060 (2.9%)	823(25%)	42.0%	45.4 (3.3%)	22.8 (8.4%)	108	43.6
7	15	0 - 61	2060 (0.97%)	1550 (10%)	79.1%	34.3 (5.0%)	20.6 (23%)	107	80.4
7	25	0 - 61	2060 (0.97%)	1240 (11%)	63.0%	34.3 (5.0%)	23.7 (8.0%)	107	64.6
7	50	0 - 61	2060 (0.97%)	560 (3.2%)	28.6%	34.3 (5.0%)	105 (0.96%)	107	36.1
9	15	0 - 50	2080 (5.3%)	1300 (4.6%)	66.3%	37.6 (4.5%)	228 (2.2%)	108	82.6
9	25	0 - 50	2080 (5.3%)	729 (2.5%)	37.2%	37.6 (4.5%)	575 (3.5%)	108	78.6
9	50	0 - 50	2080 (5.3%)	11.5 (6.1%)	0.584%	37.6 (4.5%)	1310 (3.1%)	108	95.0
			3-octyl acrylate	3-octyl acrylate	3-octyl acrylate	3-octanol	3-octanol	3-octanol	3-octanol
4	15	0 - 61	1810 (3.3%)	1530 (3.9%)	89.0%	21.9 (0.46%)	11.0 (14%)	107	90.1
4	25	0 - 61	1810 (3.3%)	1430 (6.3%)	82.8%	21.9 (0.46%)	11.0 (1.8%)	107	84.0
4	50	0 - 61	1810 (3.3%)	1080 (9.3%)	62.8%	21.9 (0.46%)	16.4 (1.2%)	107	64.3
7	15	0 - 61	1800 (3.9%)	1560 (7.7%)	90.7%	16.4 (11%)	12.8 (16%)	106	92.0
7	25	0 - 61	1800 (3.9%)	1360 (5.2%)	78.8%	16.4 (11%)	14.7 (2.7%)	106	80.2
7	50	0 - 61	1800 (3.9%)	895 (0.89%)	52.0%	16.4 (11%)	54.2 (0.0%)	106	56.7
9	15	0 - 50	1790 (2.8%)	1470 (2.0%)	85.2%	18.4 (6.5%)	96.8 (6.6%)	106	93.4
9	25	0 - 50	1790 (2.8%)	1100 (4.6%)	63.7%	18.4 (6.5%)	289 (0.69%)	106	87.7
9	50	0 - 50	1790 (2.8%)	68.3 (1.0%)	3.97%	18.4 (6.5%)	1070 (1.0%)	106	91.9
			4-octyl acrylate	4-octyl acrylate	4-octyl acrylate	4-octanol	4-octanol	4-octanol	4-octanol
4	15	0 - 61	1390 (2.9%)	1280 (2.4%)	95.9%	15.6 (0.64%)	9.17 (1.5%)	107	97.3
4	25	0 - 61	1390 (2.9%)	1210 (4.1%)	90.6%	15.6 (0.64%)	9.55 (2.1%)	107	92.0
4	50	0 - 61	1390 (2.9%)	965 (7.3%)	72.6%	15.6 (0.64%)	13.6 (0.0%)	107	74.3
7	15	0 - 61	1390 (2.2%)	1300 (6.2%)	97.7%	12.6 (3.2%)	9.72 (14%)	106	99.2
7	25	0 - 61	1390 (2.2%)	1160 (2.6%)	86.8%	12.6 (3.2%)	11.1 (0.90%)	106	88.4
7	50	0 - 61	1390 (2.2%)	830 (0.12%)	62.4%	12.6 (3.2%)	40.9 (0.0)	106	67.0
9	15	0 - 50	1380 (4.3%)	1230 (1.6%)	92.5%	13.4 (5.2%)	67.6 (9.2%)	106	100
9	25	0 - 50	1380 (4.3%)	960 (6.5%)	72.2%	13.4 (5.2%)	214 (0.47%)	105	95.3
9	50	0 - 50	1380 (4.3%)	67.5 (1.3%)	5.07%	13.4 (5.2%)	828 (2.7%)	105	93.6

(1)     Mass balance was calculated based on a 1:1 stoichiometric hydrolysis of the acrylate to the corresponding alcohols

 

Table 2. Summary of Hydrolytic Rate Constants and Calculated Half-Lives of MTDID 44428

 

Test item	pH	Temp (°C)	Elapsed Time (Days)	Rate constant k (day-1)	R^2	Calculated Half-Life (day)
2-octyl acrylate
	4	15	0 - 61	N/C^(1)	N/C^(1)	N/C^(1)
	4	25	0 - 61	0.00455	0.520	152 (98.2 - 339)^(2)
	4	50	0 - 61	0.00930	0.805	74.5 (58.2 -104)^(2)
	7	15	0 - 61	N/C^(1)	N/C^(1)	N/C^(1)
	7	25	0 - 61	0.00507	0.501	137 (84.0 - 368)^(2)
	7	50	0 - 61	0.0175	0.947	39.6 (34.9 - 45.8)
	9	15	0 - 50	0.00690	0.844	100 (74.3 - 155)^(2)
	9	25	0 - 50	0.0184	0.945	37.7 (32.2 - 45.4)
	9	50	0 - 50	0.190	0.991	3.64 (3.41 - 3.90)
3-octyl acrylate
	4	15	0 - 61	N/A^(3)	N/A^(3)	N/A^(3)
	4	25	0 - 61	N/C^(1)	N/C^(1)	N/C^(1)
	4	50	0 - 61	0.00549	0.848	126 (102 - 167)^(2)
	7	15	0 - 61	N/A^(3)	N/A^(3)	N/A^(3)
	7	25	0 - 61	0.00314	0.550	221 (141 - 512)^(2)
	7	50	0 - 61	000993	0.874	69.8 (57.3 - 89.2)^(2)
	9	15	0 - 50	N/A^(3)	N/A^(3)	N/A^(3)
	9	25	0 - 50	0.00742	0.881	93.4 (68.3 - 147)^(2)
	9	50	0 - 50	0.0789	0.981	8.78 (8.08 - 9.61)
4-octyl acrylate
	4	15	0 - 61	N/A^(3)	N/A^(3)	N/A^(3)
	4	25	0 - 61	N/A^(3)	N/A^(3)	N/A^(3)
	4	50	0 - 61	0.00377	0.574	184 (119 - 401)^(2)
	7	15	0 - 61	N/A^(3)	N/A^(3)	N/A^(3)
	7	25	0 - 61	N/A^(3)	N/A^(3)	N/A^(3)
	7	50	0 - 61	0.00716	0.705	96.8 (69.1 - 162)^(2)
	9	15	0 - 50	N/A^(3)	N/A^(3)	N/A^(3)
	9	25	0 - 50	0.00596	0.821	116 (79.2 - 218)^(2)
	9	50	0 - 50	0.0653	0.984	10.6 (9.83 - 11.5)

 (1)   Not calculated. No hydrolysis calculations will be presented as the Upper 95% confidence limit has a positive slope which may be indicative of no hydrolysis.

(2)     Extrapolated Half-Life

(3)     Not Applicable. No hydrolysis observed.

 

Table 3. Arrhenius Constants

pH	Isomer	Intercept ln k (lower 95%, upper 95%)	Slope (B) -E/R (lower 95%, upper 95%)	Activation Energy (E) kJ*mol-1 (lower 95%, upper 95%)
4	2-octyl acrylate	3.84^(1)	-2750^(1)	22.9^(1)
	3-octyl acrylate	ND^(2)	ND^(2)	ND^(2)
	4-octyl acrylate	ND^(2)	ND^(2)	ND^(2)
7	2-octyl acrylate	10.7^(1)	-4780^(1)	39.7^(1)
	3-octyl acrylate	9.12^(1)	-4440^(1)	36.9^(1)
	4-octyl acrylate	ND^(2)	ND^(2)	ND^(2)
9	2-octyl acrylate	25.7 (19.9, 31.6)	-8860 (-10600, -7090)	73.6 (59.0, 88.3)
	3-octyl acrylate	25.7^(1)	-9110^(1)	75.7^(1)
	4-octyl acrylate	25.8^(1)	-9220^(1)	76.7^(1)

1 Only two points were used in the result presented. A linear regression with two points has zero degrees of freedom which does not
allow further confidence limit calculations.
2 Not Determined. Less than two points are available for the calculation of Arrhenius constants.

Conclusions:

MTDID 44428 is a mixture of isomers. Hydrolysis half-lives ranged from 37.7 – 221 days at 25°C and pH 4, 7, and 9.

Executive summary:

A tier II and tier III hydrolysis study for MTDID 44428 was performed according to method similar to OECD Guidelines No.111: Hydrolysis as a function of pH.

The test was conducted at three pHs (pH 4.0, 7.0 and 9.0) and three temperatures (15 °C, 25 °C and 50 °C), respectively. Test samples contains 5 µg/mL of MTDID 44428 were prepared in duplicate for each pH, each temperature and each time points. The test durations were 61 days (8 time points) for pH 4 and pH 7, and 50 days (10 time points) for pH 9.  MTDID 44428 is a mixture of isomers. Three main isomers, 2- octyl acrylate, 3-octyl acrylate, and 4-octyl acrylate and the corresponding alcohol were analyzed throughout the hydrolysis study. For each pH and temperature combination, the hydrolytic rate constant, k, and hydrolytic half-life, DT50, were determined by plotting the natural logarithm of the measured concentrations of the parent isomers as a function of elapsed time, assuming the hydrolysis followed pseudo first-order reaction kinetics.

In general, hydrolytic activity appears to increase with increased temperature, increased pH, and increased linearity of the isomers. For hydrolysis at 15 °C: only 2-octyl acrylate had a calculated half-life of 100 days at 15 °C and pH 9. For hydrolysis at 25 °C: 2- octyl acrylate had calculated half-lives of 152 days, 137 days, and 37.7 days, at pH 4, 7, and 9, respectively; 3 -octyl acrylate had calculated half-lives of 221 days, and 93.4 days at pH  7 and 9,  respectively; 4 -octyl acrylate had calculated half-life of 116 days only at pH 9. For hydrolysis at 50 °C: 2- octyl acrylate had calculated half-lives of 74.5 days, 39.6 days, and 3.64 days, at pH 4, 7, and 9, respectively; 3 -octyl acrylate had calculated half-lives of 126 days, 69.8 days, and 8.78 days, at pH 4, 7, and 9, respectively; 4 -octyl acrylate had calculated half-lives of 184 days, 96.8 days, and 10.6 days, at pH 4, 7, and 9, respectively. For all isomers, hydrolysis half-lives range from 37.7 – 221 days at 25°C and pH 4, 7, and 9;  hydrolysis half-lives range from 3.64 – 184 days at 50°C and pH 4, 7, and 9.

Mass balances were calculated with the associated alcohol based on a 1:1 stoichiometric hydrolysis of the acrylate to the corresponding alcohols. The overall mass balance were 78.6 -100 % at pH 9 at all temperatures for all isomer, confirming the formation of the corresponding alcohol making up the loss of the test substance. However, mass balance for pH 4 and pH 7 dropped as the concentration of the test substance decreased. Formation of the corresponding alcohols was only observed at 50°C for pH 7, with mass balance of 36.1 - 67%. This suggests that there may be another non-hydrolytic process or an unaccounted intermediate or end point with the proposed hydrolysis pathway.

This study was conducted under GLP. However, most of calculated half-lives are extrapolated values and exceeded the last time point tested. Additionally, mass balance was not within 90% to 110%. Therefore, this study is considered reliable with restriction.

Description of key information

MTDID 44428 is a mixture of isomers. Hydrolysis half-lives of 37.7 – 221 days were determined for three main isomers at 25°C and pH 4, 7, and 9.

Additional information

Two hydrolysis studies were performed. MTDID 44428 is a mixture of isomers. Three main isomers, 2-octyl acrylate, 3-octyl acrylate, and 4-octyl acrylate were analyzed for both hydrolysis studies.

A first hydrolysis study was performed in 2019 -2020 according to OECD Guidelines No.111: Hydrolysis as a function of pH. A tier 1 study was carried out in triplicates at each pH 4, 7 and 9 and incubated in constant temperature of 50˚C in dark for 5 days, under static conditions. After 5 days, all isomers had % loss of > 90%. A tier II hydrolysis study were conducted at pH 4, 7, and 9 and at 15 °C, 25 °C and 50 °C . Results for 50 °C were reported for a period of 4 days with 6 sampling points, whereas results for 25 °C and 15 °C were reported for time 0 and 6-hour sampling points. The percentage loss of MTDID 44428 were 85% - 93.5% for all isomers over the period of 6 hours at 50 °C, independent of pH condition. The percentage loss of MTDID 44428 were 59% - 92.2% for all isomers over the period of 6 hours at 25 °C. The percentage loss of MTDID 44428 were 9.6% - 54.4% for all isomers over the 6 -hours sampling point at 15 °C. Because there were not enough sampling points at all conditions, a loss curve cannot be developed. No half-life was calculated. Additionally, the predicted hydrolysis products, 2-octanol, 3-octanol, and 4-octanol were exacted and analyzed by GC/MS/MS. However, quantitation of the hydrolysis products cannot be made due to the study was unable to develop calibration curves for the three proposed hydrolysis products. Consequently, the loss of the parent test item due to hydrolysis cannot be confirmed in the present study. Although this is a guideline study conducted under GLP compliance, the test had significant methodological deficiencies. This study is considered not reliable and a disregarded study.

 

A second hydrolysis study was performed in 2021 according to method similar to OECD Guidelines No.111: Hydrolysis as a function of pH. The main isomers and the corresponding alcohols were analyzed throughout the study. A tier II and tier III hydrolysis test was conducted at pH 4, 7 and 9 and at 15 °C, 25 °C and 50 °C over a period of 61 days (8 time points) for pH 4 and pH 7, and 50 days (10 time points) for pH 9.  For each pH and temperature combination, the hydrolytic rate constant, k, and hydrolytic half-life, DT50, were determined by plotting the natural logarithm of the measured concentrations of the parent isomers as a function of elapsed time, assuming the hydrolysis followed pseudo first-order reaction kinetics. In general, hydrolytic activity appears to increase with increased temperature, increased pH, and increased linearity of the isomers. For all isomers, hydrolysis half-lives range from 37.7 – 221 days at 25°C and pH 4, 7, and 9;  hydrolysis half-lives range from 3.64 – 184 days at 50°C and pH 4, 7, and 9. Only 2-octyl acrylate had a calculated half-life of 100 days at 15 °C and pH 9. Mass balances were calculated with the associated alcohol based on a 1:1 stoichiometric hydrolysis of the acrylate to the corresponding alcohols.The overall mass balance were 78.6 -100 % at pH 9 at all temperatures for all isomer, confirming the formation of the corresponding alcohol making up the loss of the test substance. However, mass balance for pH 4 and pH 7 dropped as the concentration of the test substance decreased. Formation of the corresponding alcohols was only observed at 50°C for pH 7, with mass balance of 36.1 - 67%. This suggests that there may be another non-hydrolytic process or an unaccounted intermediate or end point with the proposed hydrolysis pathway. This study was conducted under GLP. However, most of calculated half-lives are extrapolated values and exceeded the last time point tested. Additionally, mass balance was not within 90% to 110%. Therefore, this study is considered reliable with restriction and a key study. This study is pertinent to the fate of MTDID 44428 and may be used for Risk Assessment, Classification & Labelling, and PBT Analysis.