Reaction mass of rel-(2R,3aR,6R,7aR)-2,6-dimethyl-3a-(propan-2-yl)octahydro-1-benzofuran and rel-(2R,3aR,6S,7aR)-2,6-dimethyl-3a-(propan-2-yl)octahydro-1-benzofuran and rel-(2R,3aS,6S,7aS)-2,6-dimethyl-3a-(propan-2-yl)octahydro-1-benzofuran

Hydrolysis

Link to relevant study record(s)

Reference

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 10 November 2015 and 04 April 2016.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

The study is considered to be a reliability 1 as it has been conducted according to OECD Test Guideline 111 using the abiotic degradation method and in compliance with GLP.

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Radiolabelling:

no

Analytical monitoring:

yes

Details on sampling:

Analysis of Sample Solutions
The sample solutions were taken from the waterbath at various times and the pH of each solution recorded.
The concentration of the sample solution was determined by gas chromatography (GC).

Sample solutions
An aliquot (20 mL) of each sample was extracted with a single portion (5 mL) of iso-octane. The phases were allowed to separate and each upper organic phase was then vialled for analysis.

Sample solution matrix blanks
An aliquot (20 mL) of each unfortified buffer solution was extracted with a single portion (5 mL) of iso-octane. The phases were allowed to separate and each upper organic phase was then vialled for analysis.

Standard solutions
Duplicate standard solutions of test item were prepared in iso-octane at a nominal concentration of 100 mg/L.

Standard solution matrix blank
iso-Octane.

Buffers:

Specification of Buffer Solutions
The composition of the buffer solutions used is summarized as follows:

Buffer solution
(pH) Components Concentration
(mol dm-3)
4 Citric acid 0.06
Sodium chloride 0.04
Sodium hydroxide 0.07
7 Disodium hydrogen orthophosphate (anhydrous) 0.03
Potassium dihydrogen orthophosphate 0.02
Sodium chloride 0.02
9 Disodium tetraborate 0.01
Sodium chloride 0.02

These solutions were subjected to ultrasonication and degassing with nitrogen to minimize dissolved oxygen content.

Details on test conditions:

Performance of the Test

Preparation of the Test Solutions
Sample solutions were prepared in stoppered glass flasks at a nominal concentration of 2.0 x 10-2 g/L in the three buffer solutions. A 1% co-solvent of acetonitrile was used to aid solubility.
The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility.
The test solutions were split into individual vessels for each data point.
The solutions were shielded from light whilst maintained at the test temperature.

Preliminary Test
Sample solutions at pH 4 and 7 were maintained at 50.0 ± 0.5 °C for a period of 356 hours.
Sample solutions at pH 9 were maintained at 50.0 ± 0.5 °C for a period of 120 hours.

Duration:

356 h

pH:

4

Temp.:

50 °C

Initial conc. measured:

0.02 g/L

Remarks:

The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility.

Duration:

356 h

pH:

7

Temp.:

50 °C

Initial conc. measured:

0.02 g/L

Remarks:

The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility.

Duration:

120 h

pH:

9

Temp.:

50 °C

Initial conc. measured:

0.02 g/L

Remarks:

The concentration of each solution did not exceed the lesser of 0.01 mol/L or half the water solubility.

Positive controls:

not specified

Negative controls:

not specified

Preliminary study:

The mean peak areas relating to the standard and sample solutions are shown in the tables in the section below "Any other information on results, inc. table":

Transformation products:

not measured

Key result

pH:

4

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

other: Less than 10% hydrolysis over a 5 day period at 50 °C, considering the full data set, equivalent to a half-life greater than 1 year at 25 °C.

Key result

pH:

7

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

other:

Remarks:

Less than 10% hydrolysis over a 5 day period at 50 °C, considering the full data set, equivalent to a half-life greater than 1 year at 25 °C.

Key result

pH:

9

Temp.:

25 °C

DT50:

> 1 yr

Type:

not specified

Remarks on result:

other: Less than 10% hydrolysis over a 5 day period at 50 °C, considering the full data set, equivalent to a half-life greater than 1 year at 25 °C.

Solution	Mean Peak Area
Standard 102 mg/L	1.0163 x 10^7
Standard 101 mg/L	1.0239 x 10^7
Initial Sample A, pH 4	8.1798 x 10^6
Initial Sample B, pH 4	8.2304 x 10^6
Initial Sample A, pH 7	8.1829 x 10^6
Initial Sample B, pH 7	8.1459 x 10^6
Initial Sample A, pH 9	8.0707 x 10^6
Initial Sample B, pH 9	7.8563 x 10^6
Standard 102 mg/L	1.0461 x 10^7
Standard 106 mg/L	1.1139 x 10^7
120 Hour Sample A, pH 4	5.0254 x 10^6
120 Hour Sample B, pH 4	7.5839 x 10^6
120 Hour Sample A, pH 7	6.6932 x 10^6
120 Hour Sample B, pH 7	7.2373 x 10^6
120 Hour Sample A, pH 9	7.6126 x 10^6
120 Hour Sample B, pH 9	7.9589 x 10^6
Standard 107 mg/L	1.1324 x 10^7
Standard 109 mg/L	1.1640 x 10^7
188 Hour Sample A, pH 4	7.6566 x 10^6
188 Hour Sample B, pH 4	8.0808 x 10^6
188 Hour Sample A, pH 7	7.6258x 10^6
188 Hour Sample B, pH 7	8.1018 x 10^6
Standard 101 mg/L	1.0763 x 10^7
Standard 101 mg/L	1.0947 x 10^7
365 Hour Sample A, pH 4	8.0469 x 10^6
365 Hour Sample B, pH 4	7.5837 x 10^6
365 Hour Sample C, pH 4	7.7524 x 10^6
365 Hour Sample D, pH 4	7.5778 x 10^6
365 Hour Sample A, pH 7	7.3664 x 10^6
365 Hour Sample B, pH 7	7.1804 x 10^6
365 Hour Sample C, pH 7	7.2591 x 10^6
365 Hour Sample D, pH 7	6.9490 x 10^6

The test item concentrations at the given time points are shown in the following tables:

 

 pH 4 at 50.0 ± 0.5 ºC

 

Timepoint (hours)		Replicate		Concentration (g/L)		% of Mean Initial Concentration
Initial		A		2.03 x 10^-2		99.7
		B		2.05 x 10^-2		100.3
120		A		1.21 x 10^-2		59.2[1]
		B		1.82 x 10^-2		89.4
188		A		1.80 x 10^-2		88.3
		B		1.90 x 10^-2		93.2
356		A		1.87 x 10^-2		91.9
		B		1.77 x 10^-2		86.6
		C		1.81 x 10^-2		88.5
		D		1.76 x 10^-2		86.5

Result:            Less than 10% hydrolysis over a 5 day period at 50 °C, considering the full data set, equivalent to a half-life greater than 1 year at 25 °C.

[1]Identified as a statistically significant outlier, Grubs’ test, P = 0.05.

pH 7 at 50.0 ± 0.5 ºC

 

Timepoint (hours)	Replicate	Concentration (g/L)	% of Mean Initial Concentration
Initial	A	2.03 x 10^-2	100.2
	B	2.02 x 10^-2	99.8
120	A	1.61 x 10^-2	79.3
	B	1.74 x 10^-2	85.7
188	A	1.79 x 10^-2	88.4
	B	1.90 x 10^-2	93.9
356	A	1.72 x 10^-2	84.5
	B	1.67 x 10^-2	82.4
	C	1.69 x 10^-2	83.3
	D	1.62 x 10^-2	79.8

Result:            Less than 10% hydrolysis over a 5 day period at 50 °C, considering the full data set, equivalent to a half-life greater than 1 year at 25 °C.

 pH 9 at 50.0 ± 0.5 ºC

 

Timepoint (hours)	Replicate	Concentration (g/L)	% of Mean Initial Concentration
Initial	A	2.01 x 10^-2	101.3
	B	1.95 x 10^-2	98.7
120	A	1.83 x 10^-2	92.1
	B	1.91 x 10^-2	96.4

 

Result:            Less than 10% hydrolysis after 5 days at 50 °C, equivalent to a half-life greater than 1 year at 25 °C.

 Validation

The linearity of the detector response with respect to concentration was assessed over the nominal concentration range of 10 to 200 mg/L. This was satisfactory with a first order correlation coefficient of 0.9998 being obtained.

 

Procedural recoveries of fortified sample solutions for each pH condition were undertaken and assessed as adequate for the test. The results of this validation work are summarized in the following table. It was not considered necessary or relevant for concentrations to be been corrected for recovery of analysis.

 Table        

 

pH	Nominal Concentration (g/L)	Number of Recoveries Performed (n)	Mean Recovery (%)	Recovery Range (%)	Standard Deviation (%)
4	2.0 x 10^-2	5	98.1	95.8 to 99.8	1.62
7	2.0 x 10^-2	5	97.3	94.7 to 99.2	1.97
9	2.0 x 10^-2	5	95.6	94.7 to 97.0	0.87

Validity criteria fulfilled:

yes

Remarks:

Please see "Any other information on results, incl tables" for further details.

Conclusions:

The estimated half-life at 25 °C of the test item was greater than 1 year at pH 4, 7 and 9 at a temperature of 25°C.

Executive summary:

The hydrolysis half-life of the test substance IFF 215 (Floriane), was determined to be greater than 1 year at pH 4, 7 and 9 at a temperature of 25°C according to OECD Guidelines for Testing of Chemicals using the abiotic degradation, hydrolysis as a function of pH method.

Description of key information

The hydrolysis half-life of the test substance IFF 215 (Floriane), was determined to be greater than 1 year at pH 4, 7 and 9 at a temperature of 25°C according to OECD Guidelines for Testing of Chemicals using the abiotic degradation, hydrolysis as a function of pH method.

Key value for chemical safety assessment

Half-life for hydrolysis:

1 yr

at the temperature of:

25 °C