1,1,2,2,3,3,4,4,4-nonafluoro-N-(2-hydroxyethyl)-N-methylbutane-1-sulphonamide

Hydrolysis

Administrative data

Endpoint:

hydrolysis

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August 02, 2002 - August 20, 2002

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted under GLP with acceptable calculation methods.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 111 (Hydrolysis as a Function of pH)

Deviations:

yes

Remarks:

deviation on half life calcualtion method.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

C4 sulfonamido alcohol

IUPAC Name:

C4 sulfonamido alcohol

Details on test material:

- Name of test material (as cited in study report):N-MeFBSE alcohol
- Substance type: single component
- Physical state: White Crystals
- Stability under test conditions: Stable
- Storage condition of test material: Ambient

Radiolabelling:

no

Study design

Analytical monitoring:

yes

Details on sampling:

Pre-cleaned, amber 40-mL Teflon sealed crew-top bottles were used as test containers. The test containers were sparged with argon for
30 seconds.
Buffered aqueous solutions at nominal pH levels of 4, 7, and 9 were prepared. The buffer solutions were sparged with argon for 10 minutes.
Triplicate test samples of C4 sulfonamido alcohol were prepared by adding appropriate amount of C4 sulfonamido alcohol to the test containers containing 5 mL of buffer solution to yield a concentration of approximately 5 ppm.
The day 0 samples were quenched immediately with 30 mL THF.
The day 5 samples were incubated at 50 °C in an incubator that swirls samples at approximately 150 RPM. At the end of the day 5, the
samples were quenched with 30 mL THF.
Post hydrolysis spikes were added at appropriate levels.
The samples were refrigerated at 4°C until removed to add internal standard, and aliquot for analysis using LC/MS.

Buffers:

pH 4 Buffer: 4.0 mL of 0.1N NaOH/ 500 mL 0.1 M K+Biphthalate; pH measured at day 5: 3.9
pH 7 Buffer: 296 mL 0.1 N NaOH/500 mL of 0.1N K+Phosphate; pH measured at day 5: 6.6
pH 9 buffer: 125 mL 0.1M Borax/ 1.2 N HCl as needed, pH measured at day 5: 8.5

Details on test conditions:

TEST SYSTEM
- Type, material and volume of test flasks, other equipment used: Pre-cleaned, amber 40-mL Teflon sealed crew-top bottles
- Measures taken to avoid photolytic effects: amber vials
- Measures to exclude oxygen: Buffers of pH 4, 7, and 9 were sparged with Argon for at least ten minutes prior to transfer into Argon
sparged vials. The test containers were sparged with argon for 30 seconds.

TEST MEDIUM
- Volume used/treatment: 5 mL buffer solution at pH 4, 7, 9
- Renewal of test solution: None
- Identity and concentration of co-solvent: no co-solvent

OTHER TEST CONDITIONS
- Adjustment of pH: None
- Dissolved oxygen: purged with Argon
Tetrahydrofuran (THF) will be added post hydrolysis as a quenching solvent

Duration of test

Duration:

5 d

Temp.:

50 °C

Initial conc. measured:

ca. 5 mg/L

Number of replicates:

three replicates.

Positive controls:

no

Negative controls:

no

Results and discussion

Transformation products:

yes

Identity of transformation products

Identity of transformation products 1

No.:

#1

Reference

Reference substance name:

Unnamed

IUPAC name:

N-MeFBSA

Identifier:

common name

Identity:

N-MeFBSA

Identity of transformation products 2

No.:

#2

Reference

Reference substance name:

Unnamed

IUPAC name:

FBSA

Identifier:

common name

Identity:

FBSA

Identity of transformation products 3

No.:

#3

Reference

Reference substance name:

Unnamed

IUPAC name:

PFBS

Identifier:

common name

Identity:

PFBS

Identity of transformation products 4

No.:

#4

Reference

Reference substance name:

Unnamed

IUPAC name:

PFBA

Identifier:

common name

Identity:

PFBA

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

- Formation and decline of each transformation product during test: Fig.1

Dissipation DT50 of parent compound

Dissipation DT50 of parent compound 1

pH:

7

Temp.:

25 °C

DT50:

>= 1.67 yr

Type:

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

Remarks on result:

other: Statistical Evaluation of standard deviation

Dissipation DT50 of parent compound 2

pH:

7

Temp.:

25 °C

DT50:

>= 2.26 yr

Type:

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

Remarks on result:

other: LOQ of hydrolysis product PFBS

Details on results:

Triplicate samples contain 5 ppm of C4 sulfonamido alcohol were incubated at 50 °C for days at pH 4, 7, 9. C4 sulfonamido alcohol and its hydrolysis products PFBA, PFBS, FBSA, and N-MeFBSA were monitored at day 0 and day 5. No significant changes in the C4 sulfonamido alcohol concentration over the test period of 5 days at pH 4, 7, and 9 were observed (Table 1). The concentrations of the hydrolysis products were all below their respective limit of quantitation (LOQ) (Table 2).

In order to calculate the hydrolysis half life of C4 sulfonamido alcohol, two estimation methods were used to calculate the hydrolysis half life:
1) Statistical Evaluation of standard deviation to Determine the Reliability of Rate Constants Determined over all pH levels was used.
Measured C4 sulfonamido alcohol concentration range from 775.46 ng/mL to 848.54 ng/mL (exclude one statistical outlier) for day 0 and day 5 over all the pH levels. The overall average measured concentration was 805.33 ng/mL; with standard deviation of 22.89. Based on the eq. 1, the maximum hydrolysis rate constant is calculated to be 0.01137 day-1, resulting in half life of 60.98 days at 50 °C, equivalent to half life ≥ 1.67 years at 25 °C (Table 3).

2) The measured concentration of the potential hydrolysis product PFBS provide a second estimate for the half life of C4 sulfonamido alcohol. In the second method, the minimum pseudo first order hydrolytic half life of C4 sulfonamido alcohol was calculated by estimating how fast the C4 sulfonamido alcohol might degrade to generate PFBS. This estimate assumes that PFBS is the only hydrolytic product formed and that it is present at the concentration of the calculated limit of quantification (LOQ) of 25 ng/mL for PFBS, resulting a half life of ≥ 82.4 days at 50 °C (Table 3), equivalent to half life of ≥ 2.26 years at 25 °C (Table 3).

Any other information on results incl. tables

Table 1. C4 sulfonamido alcohol Concentration (ng/mL) (E02-0813)

	Rep 1 (ng/mL)	Rep 2 (ng/mL)	Rep 3 (ng/mL)	Avg  (ng/mL)	stdev	% RSD
pH = 4
Day 0	802.18	782.28	775.46	786.64	13.88	1.76%
Day 5	775.74	797.68	805.43	792.95	15.4	1.94%
pH = 7
Day 0	843.84	644.61*	848.54	779.0	116.4	14.9%
Day 5	796.2	806.14	790.19	797.51	8.05	1.01%
pH = 9
Day 0	790.44	793.62	793.28	792.4	1.75	0.221%
Day 5	825.35	829.77	834.43	829.85	4.54	0.547%
Overall average of all measurements excluding the outlier				805.33
Overall standard deviation of all measurements excluding the outlier					22.89

 

*statistical outlier, not included in calculating half-life.

 

Table 2. Summary of PFBA, PFBS, FBSA, and N-MeFBSA Concentration

from the C4 sulfonamido alcohol hydrolysis (E02-0813)

Sample	pH 4 (ng/mL)	pH 7 (ng/mL)	pH 9 (ng/mL)
PFBA	< 24.75	< 24.75	< 9.898
PFBS	< 25.00	< 25.00	< 10.00
FBSA	< 9.997	< 9.997	< 9.997
N-MeFBSA	< 10.00	< 10.00	< 10.00

 

 

Table 3. C4 sulfonamido alcohol hydrolysis half-Life summary (E02-0813)

1)     Statistical Evaluation of standard deviation to Determine the Reliability of Rate Constants Determined over all pH levels
Half life equation	Tp(1/2)  ≥  (Tp ½) min = ln (2)  / (Kp)max = ln (2) µpδ t / 2 σp
Overall average of all measurements excluding the outlier ( µp)	805.33 ng/mL
Overall standard deviation of all measurements excluding the outlier (2 σp)	22.89
δ t (days)	5
Maximum rate constant (Kp) max	K(p) max = 0.01137 day-1
Half life at 50 °C	60.98 days
Half life at 25 °C	609.8 days
Half life at 25 °C	≥ 1.67 years
2)     Determination of the half-life using  C4 sulfonamido alcohol Initial Concentration and the limit of quantification (LOQ) of PFBS
Half life equation	Tp(1/2)  ≥ δ t [P0] ln 2 / A LOQ
PFBS LOQ (ng/mL)	25.00 ng/mL
PFBS LOQ (mol/L)	8.361E-08
Molecular weight	299
Expected concentration of N-MeFBSE alcohol (ng/mL)	71.5
P0 (mol/L)	1.989E-06
A LOQ(mol/L)	8.361E-08
δ t (days)	5
Half life at 50 °C	≥ 82.4 days
Half life at 25 °C	≥ 824 days
Half life at 25 °C	≥ 2.26 years

Applicant's summary and conclusion

Validity criteria fulfilled:

yes

Conclusions:

No significant changes in the C4 sulfonamido alcohol concentration over the test period of 5 days at pH 4, 7, and 9 were observed. A minimum hydrolytic half life of 1.67 years at 25 °C was calculated based on the evaluation of the standard deviation of measured concentration determined at pH 4, 7, 9. An alternative calculation that consides the initial C4 sulfonamido alcohol concentration and the LOQ of the possible hydrolysis product PFBS, yields a minimum hydrolytic half life of 2.26 years. These hydrolytic rates are independent of pH.

Executive summary:

Triplicate samples contain 5 ppm of C4 sulfonamido alcohol were incubated at 50 °C for days at pH 4, 7, 9. C4 sulfonamido alcohol and its hydrolysis products PFBA, PFBS, FBSA, and N-MeFBSA were monitored at day 0 and day 5. No significant changes in the C4 sulfonamido alcohol concentration over the test period of 5 days at pH 4, 7, and 9 were observed. The concentrations of the hydrolysis products, PFBA, PFBS, FBSA, and N-MeFBSA, were all below their respective limit of quantitation (LOQ).

In order to calculate the hydrolysis half life of C4 sulfonamido alcohol, two estimation methods were used to calculate the hydrolysis half life: 1) Statistical Evaluation of standard deviation to Determine the Reliability of Rate Constants Determined over all pH levels was used. 2) The measured concentration of the potential hydrolysis product PFBS provide a second estimate for the half life of C4 sulfonamido alcohol.

Based on the evaluation of the standard deviation of measured concentrations determined at pH 4, 7, 9, C4 sulfonamido alcohol has a minimum hydrolytic half life of 1.67 years at 25 °C. An alternative calculation that consides the initial C4 sulfonamido alcohol concentration and the LOQ of the possible product PFBS, yields a minimum hydrolytic half life of 2.26 years. These hydrolytic rates are independent of pH.

This is a guideline study conducted under GLP. The estimation methods meet generally accepted calculation method. Therefore, it is considered reliable with acceptable restriction.