Propanenitrile, 2,3,3,3-tetrafluoro-2-(trifluoromethyl)-

Henry's Law constant

Link to relevant study record(s)

Reference

Endpoint:

Henry's law constant

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 December 2013 - 17 December 2013

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

according to guideline

Guideline:

other: calculation based on experimental data

Deviations:

not applicable

Principles of method if other than guideline:

Henry's Law Constant (unitless) was determined by measuring the L-21609 concentrations in gas-phase and in aqueous-phase for a given test system vessel at equilibrium conditions and at ambient temperature and pressure.

GLP compliance:

yes

H:

25 900 dimensionless

Temp.:

23 °C

Atm. press.:

760 mm Hg

Henry's Law constant (HLC) result is reported as a dimensionless ratio of headspace concentration of L-21609 over aqueous phase concentration.

Average HLC results were 13400, 22500, and 41700 for the 70%, 50% and 30% headspace ratio, respectively (Table 1). The %RSDs were 46%, 25% and 14% for the 70%, 50% and 30% headspace ratio, respectively (Table 1). The average Henry's Law constant for L-21609 was 25900, with %RSD of 51% (Table 1). The large %RSDs were due to the large variation observed in the water concentration measurement (Table 3). The Henry's Law constant expressed as log HLC is 4.4 ±0.3, with %RSD of 5.9% (Table 2).   The three different headspace to water ratios exhibited different HLC values at each time point. The vials with 70% headspace/water ratio, which were also the vials with the largest molar amount of L-21609 dosed, produced the lowest measured HLC values. Since the concentration (ng/cc) of dosed headspace was constant for each of the study vials, the total number of mols of L-21609 available in the test system vial was found to be the key driver for transport of L-21609 to the aqueous phase. Figure 1 displays the dependence of the measured log HLC values on the molar amount of L-21609 dosed into the test system vial. The plot indicates that partitioning to the headspace is strongly favored as the molar amount of L-21609 decreases in the closed test system vessel.

Large variability was observed in the L-21609 concentration measurements in water. The variability of the HLC measurements was attributed to the possible hydrolysis of the nitrile to the amide, since an additional peak was observed in aqueous sample chromatograms that suggested the nitrile was hydrolyzing to form the corresponding amide. This is in agreement with another study GLP13-0008 “Water Solubility Determination of L-21609”, which also observed the same hydrolysis product.

All measured water concentrations of L-21609 were approximately 0.67 - 9.0 ng/mL, which was below the measured water solubility of 272 ng/mL. These water levels indicate that the L-21609 dosing gas did not produce a saturated system at equilibrium.

Henry’s Law constants were also measured for tetrafluoroethylene (TFE) using the same analytical approach for L-21609 to demonstrate the validity of the analytical techniques. All measured water concentrations of TFE were below 100 ng/mL, which was below the water solubility of 160,000 ng/mL indicating that the TFE dosing gas did not produce a saturated system at equilibrium. The log(Overall Average HLC) for TFE was 1.6. The log (HLC) value reported in literature for TFE is 1.4. The measured value for TFE was within ±15% of literature value.

Table 1.  L-21609 Henry’s Law Constant (HLC) Determinations for Individual Test System Vials.

		70% Headspace	50% Headspace	30% Headspace
Time Point 1 (Four Days)	Rep 1	14100	26400	47100
	Rep 2	21800	24600	42500
	Average	17900	25500	44800
	RPD	^(1)43%	7.0%	10%
Time Point 2 (Five Days)	Rep 1	16500	27000	49400
	Rep 2	21300	30400	44200
	Average	18900	28700	46800
	RPD	25%	12%	11%
Time Point 3 (Six Days)	Rep 1	6450	16500	33700
	Rep 2	8220	17500	37600
	Average	7330	17000	35700
	RPD	24%	6.1%	11%
Time Point 4 (Eleven Days)	Rep 1	6800	22400	44900
	Rep 2	12300	15000	34100
	Average	9570	18700	39500
	RPD	^(1)58%	^(1)39%	27%
Average Headspace Ratio HLC		13400	22500	41700
RSD		^(2)46%	25%	14%
Overall Average HLC		25900
Overall RSD		^(3)51%

(1)    No criteria for intra-day HLC precision as a function of headspace ratio was specified in the study protocol.  However, the reported precision, measured as RPD, exceeded 30%.

(2)    No criteria for inter-day HLC precision as a function of headspace ratio was specified in the study protocol.  However, the reported precision, measured as RSD, exceeded 30%.

(3)    The reported precision exceeds 30% RSD.  The precision of the overall measurement was largely impacted by the discrete HLC results as a function of headspace ratio.

Table 2.  Summary of log(HLC) Results for L-21609.

		70% Headspace	50% Headspace	30% Headspace
Time Point 1 (Four Days)	Rep 1	4.1	4.4	4.7
	Rep 2	4.3	4.4	4.6
	log(Average HLC)	4.3	4.4	4.7
	RPD (log HLC)	4.4%	0.69%	0.95%
Time Point 2 (Five Days)	Rep 1	4.2	4.4	4.7
	Rep 2	4.3	4.5	4.6
	log(Average HLC)	4.3	4.5	4.7
	RPD (log HLC)	2.6%	1.1%	1.0%
Time Point 3 (Six Days)	Rep 1	3.8	4.2	4.5
	Rep 2	3.9	4.2	4.6
	log(Average HLC)	3.9	4.2	4.6
	RPD (log HLC)	2.7%	0.62%	1.0%
Time Point 4 (Eleven Days)	Rep 1	3.8	4.3	4.7
	Rep 2	4.1	4.2	4.5
	log(Average HLC)	4.0	4.3	4.6
	RPD (log HLC)	6.5%	4.1%	2.6%
log(Headspace%, Average HLC)		4.1	4.4	4.6
RSD		5.1%	2.6%	1.4%
log(Overall Average HLC)		4.4 ± 0.3
RSD		5.9%
Observed Range of Individual Measurements		3.8 – 4.7

Table 3. L-21609 concentrations in Water and Headspace.

		Time Point 1,	70% Headspace	Time Point 1,	50% Headspace	Time Point 1,	30% Headspace
		Rep 1	Rep 2	Rep 1	Rep 2	Rep 1	Rep 2
Water Conc. (ng/mL)	Average^(1)	2.89	1.93	1.45	1.66	0.803	0.965
	%RPD^(1)	^(1)35	14	6.9	^(1)39	9.1	8
Headspace Conc. (ng/mL)	Average^(1)	40700	42000	38300	40900	37800	41000
	%RPD^(1)	2.6	9.6	2.1	6.2	0.36	5.4
HLC		14100	21800	26400	24600	47100	42500
log HLC		4.1	4.3	4.4	4.4	4.7	4.6
		Time Point 2,	70% Headspace	Time Point 2,	50% Headspace	Time Point 2,	30% Headspace
		Rep 1	Rep 2	Rep 1	Rep 2	Rep 1	Rep 2
Water Conc. (ng/mL)	Average^(1)	2.6	2.04	1.6	1.4	0.755	0.817
	%RPD^(1)	15	8.2	^(1)32	20	22	22
Headspace Conc. (ng/mL)	Average^(1)	42900	43400	43100	42400	37300	36100
	%RPD^(1)	2.9	0.51	2.7	5	0.6	2.9
HLC		16500	21300	27000	30400	49400	44200
log HLC		4.2	4.3	4.4	4.5	4.7	4.6
		Time Point 3,	70% Headspace	Time Point 3,	50% Headspace	Time Point 3,	30% Headspace
		Rep 1	Rep 2	Rep 1	Rep 2	Rep 1	Rep 2
Water Conc. (ng/mL)	Average^(1)	6.55	4.61	2.66	2.36	1.15	0.915
	%RPD^(1)	^(2)69	NA	NA	^(2)37	14	4.5
Headspace Conc. (ng/mL)	Average^(1)	42200	37900	43900	41300	38700	34400
	%RPD^(1)	5.3	1.6	10	3.2	5.7	1.6
HLC		6450	8220	16500	17500	33700	37600
log HLC		3.8	3.9	4.2	4.2	4.5	4.6
		Time Point 4,	70% Headspace	Time Point 4,	50% Headspace	Time Point 4,	30% Headspace
		Rep 1	Rep 2	Rep 1	Rep 2	Rep 1	Rep 2
Water Conc. (ng/mL)	Average^(1)	6.34	3.67	2.03	3.02	0.789	0.975
	%RPD^(1)	^(1)83	18	5.3	2.4	5.8	15
Headspace Conc. (ng/mL)	Average^(1)	43100	45300	45300	45300	35400	33300
	%RPD^(1)	6.1	8.7	3.6	8.4	3.8	0.29
HLC		6800	12300	22400	15000	44900	34100
log HLC		3.8	4.1	4.3	4.2	4.7	4.5

(1)    Average and RPD of duplicate of aliquots.

Conclusions:

The log Henry's Law constant (log HLC) for L-21609 was determined to be 4.4 ± 0.3 at 23 °C.

Executive summary:

The Henry's Law constant of L-21609 was determined by the ratio of headspace concentration over aqueous phase concentration.

 

Duplicate test vessels were filled with water and dosed with L-21609 gas at each of three different headspace:water ratios (70%, 50% and 30%). The vials were incubated for 4, 5, 6 and 11 days at ambient temperature. Both the headspace and the water phase for each vial were sampled and analyzed in duplicate using purge and trap gas chromatography/mass spectrometry (GC/MS). The average measured gas phase and water phase concentrations were used to calculate Henry's Law constant for L-21609 for each test vessel.

 

Under the experimental conditions (23°C) of this study, the average measured log HLC for L-21609 ranged from 3.8 to 4.7 depending on the total moles of L-21609 dosed into the closed test system vessel.The overall average log HLC for the three different headspace ratios investigated was 4.4 ± 0.3 (RSD=5.9%). Partitioning to the headspace is favored when the total moles of L-21609 is decreased. Aqueous measurements suggest that the L-21609 partially hydrolyzes to the corresponding amide after partitioning into the water from the headspace. 

 

This study was conducted under GLP compliance with accepted method. However, large variation (%RSD > 30) was found for the concentration of L-21609 measured in water, attributed to the possible hydrolysis of the nitrile to the amide. Therefore, it is considered reliable with restrictions, and is acceptable for assessment.

Description of key information

log Henry's Law constant (log HLC) is 4.4 ± 0.3 at 23 °C. This value can be expressed as 5.97E7 Pa*m³/mol

Key value for chemical safety assessment

Henry's law constant (H) (in Pa m³/mol):

59 700 000

at the temperature of:

23 °C

Additional information

The Henry's Law constant was determined by the ratio of headspace concentration over aqueous phase concentration.

Duplicate test vessels were filled with water and dosed with 5000 ppmv gas at each of three different headspace:water ratios (70%, 50% and 30%). The vials were incubated for 4, 5, 6 and 11 days at ambient temperature. Both the headspace and the water phase for each vial were sampled and analyzed in duplicate using purge and trap gas chromatography/mass spectrometry (GC/MS). The average measured gas phase and water phase concentrations were used to calculate Henry's Law constant for each test vessel.

Under the experimental conditions (23°C) of this study, the average measured log HLC for L-21609 ranged from 3.8 to 4.7 depending on the total moles of gas dosed into the closed test system vessel. The overall average log HLC for the three different headspace ratios investigated was 4.4 ± 0.3 (RSD=5.9%).  Partitioning to the headspace is favored when the total moles of gas is decreased.  Aqueous measurements suggest that the C4 F-isonitrile partially hydrolyzes to the corresponding amide after partitioning into the water from the headspace.  

This study was conducted under GLP compliance with accepted method. However, large variation (%RSD > 30) was found for the concentration measured in water,  attributed to the possible hydrolysis of the nitrile to the amide. Therefore, it is considered reliable with restrictions, and is acceptable for assessment.