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

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 20, 2014 - January 28, 2014

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Guideline study conducted under GLP with acceptable restriction

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)

Deviations:

yes

Remarks:

The guideline typically applies to substances that are solid or liquid at ambient conditions; however, the L-21609 test substance is a gas at ambient conditions. In addition, L-21609 will hydrolyze in water and will likely react with n-octanol.

Principles of method if other than guideline:

A three-phase (gas, water, and n-octanol) test system was used to create forced conditions (great excess of test substance). A short study duration was used to minimize the effects of hydrolysis and reaction.

GLP compliance:

yes

Type of method:

shake-flask method to: flask method

Partition coefficient type:

octanol-water

Analytical method:

gas chromatography

Type:

log Pow

Partition coefficient:

4.3

Temp.:

24 °C

Remarks on result:

other: pH was not determined

Details on results:

Log Kow reported to be 4.3 ± 0.2 (RSD = 4.9%).

The reported concentrations for L-21609 in the water phase ranged from 0.643 to 3.25 ng/mL (Table 2). These values were less than the water solubility concentration of 272 ng/mL and were indicative of unsaturated equilibrium conditions.

L-21609 is not stable in the presence of n-octanol over a 48-hour time frame. The headspace analyses of the individual study samples confirmed the presence of excess gas-phase L-21609 in the test system vials after mixing and phase separation. The measured levels of L-21609 in the n-octanol fractions in the study samples were very consistent from vial to vial, independent of the n-octanol to water ratio (Average Concentration=25,700 ng/mL, RSD=12%, N=12). All study sample vials were aliquoted for analysis within a five-hour window after dosing. The Post-Study n-octanol stability samples were held for 48 hours to account for the time that analysis vials waited on the purge and trap autosampler. Once aliquoted into the analysis vial with ample headspace, it is plausible that the L-21609 partitioned out of the n-octanol into the headspace.

The calculated Kow values ranged from 9810 to 35,000, with the most of the variability coming from the water measurements (Table 3). Although the L-21609 may have been constantly degrading over the course of the study via hydrolysis or other chemical reaction, the resultant measurements suggested that a steady-state condition was achieved at the time aliquots were collected for analysis.

This study was intended to obtain the maximum achievable log(Kow) for L-21609. By using forced conditions (great excess of test substance) and a short study duration (less than five hours between dosing and aliquoting for analysis), the effects of L-21609 reactivity with both water and n-octanol were minimized and consistent measurements of Kow were obtained within the data quality objectives.

Table 2: L-21609 concentrations 

L-21609 concentration in water
Ratio (n-Octanol: Aqueous)	Replicate	1^staliquot (ng/mL)	2^ndaliquot (ng/mL)	Average Conc. in water (ng/mL)	% RPD
1:1	1	2.15	3.25	2.70	41
	2	1.11	1.12	1.11	1.2
1:2	1	1.05	1.06	1.06	0.95
	2	0.991	0.643	0.817	43
2:1	1	1.29	N/A	1.29	N/A
	2	4.86^(1)	N/A	4.86^(1)	N/A
L-21609 concentration in n-octanol
Ratio (n-Octanol: Aqueous)	Replicate	1^staliquot (ng/mL)	2^ndaliquot (ng/mL)	Average Conc. in octanol (ng/mL)	% RPD
1:1	1	26800	26300	26500	1.8
	2	25200	24400	24800	3.5
1:2	1	30200	28400	29300	6.1
	2	29500	27700	28600	6.1
2:1	1	24700	23600	24200	4.6
	2	20600	21500	21100	4.3
(1)    Replicate 2 was not reported due to observed cross contamination of n-octanol into the water aliquots at the time of analysis.  The %RPD was not calculated.

 

Table 3: n-Octanol/Water Partition Coefficient Log(Kow) for L-21609     

 

Ratio (n-Octanol: Water)	Rep	Avg. L-21609 in water phase (ng/mL)	Avg. L-21609 in octanol phase (ng/mL)	Kow	log Kow	Average log Kow	% RPD
1:1	1	2.70	26500	9810	4.0	4.2	8.5
	2	1.11	24800	22200	4.3
1:2	1	1.06	29300	27700	4.4	4.5	2.3
	2	0.817	28600	35000	4.5
2:1	1	1.29	24200	18800	4.3	4.3	N/A^(1)
	2	Not reported^(1)	21100	Not reported^(1)	Not reported^(1)
Overall average log Kow						4.3 ± 0.2
Overall RSD% (log Kow) N=5						4.9
(1)    Replicate 2 was not reported due to observed cross contamination of n-octanol into the water aliquots at the time of analysis.  The %RPD was not calculated

Conclusions:

The Log(Kow) for gas-phase L-21609 was measured to be 4.3 at 24° C under the conditions of this study.

Executive summary:

The n-Octanol/Water Partition Coefficient (log Kow) of L-21609 was conducted according to U.S EPA guidance document OPPTS 830.7550 "Partition Coefficient (n-Octanol/Water), Shake Flask Method".

 

Duplicate samples of L-21609 were prepared in each of the three octanol/water ratios (1:1, 1:2, and 2:1). All test vessels contained 12.5 mL of headspace. The test vessels were dosed with L-21609 gas standard. All vials were then rotated 180° about their transverse axis for 100 times for five minutes, then placed, inverted, on an orbital shaker at ambient temperature at a setting of 50 RPM for two hours. The vials were centrifuged upright for a total of 10 minutes at a setting of 1000 RPM. Aliquots from the headspace, aqueous and n-octanol phases were carefully removed and analyzed separately using GC/MS.

 

Log Kow for L-21609 was determined to be 4.3 ± 0.2 under the conditions of this study where excess L-21609 test substance was present in the test system vials producing an observed steady-state condition at the time when the n-octanol and water aliquots were sampled.

 

This is a guideline study conducted under GLP compliance. L-21609 test substance is a gas at ambient conditions. In addition, L-21609 will hydrolyze in water and may react with n-octanol. A three-phase (gas, water, and n-octanol) test system was used to determine the maximum achievable log Kow for L-21609 by using forced conditions (great excess of test substance) and a short study duration to minimize the effects of hydrolysis and reaction. Therefore, it is considered reliable with acceptable restrictions.

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 23, 2020 - December 17, 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

Deviations:

no

GLP compliance:

yes

Type of method:

flask method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

- Name of test material (as cited in study report): MTDID 37480
- Physical state: White solid at ambient temperature (22-23°C)
- Analytical purity: 97.7%
- Expiration date of the lot/batch: October 30, 2021

Analytical method:

gas chromatography

mass spectrometry

Key result

Type:

log Pow

Partition coefficient:

1.7

Temp.:

23.9 °C

Remarks on result:

other: pH not measured

Key result

Type:

Pow

Partition coefficient:

47.9

Temp.:

23.9 °C

Remarks on result:

other: pH not measured

Remarks:

% RSD = 2.64

Details on results:

This study was initially performed using a dosing solution of 0.04 M, which is four times the criteria for dilute solutions as defined in OPPTS 830.7550 and OECD 107. The study was repeated using a dosing solution of 0.01 M. All measured water aliquots were less than the saturated water solubility of 17800 µg/mL indicating unsaturated equilibrium conditions. Results from both studies are provided in Table 1.

For 0.04M dosed system, measured Kow ranged from 48.3 to 51.6. For the 0.01M dosed system, measured Kow ranged from 44.2 to 48.6. The average Kow measured was 50.0 (2.5% RSD) and 45.7 (3.6% RSD) for the 0.04 M and 0.01 M studies, respectively. Both studies produced a log Kow value of 1.7. Given that the range of individual measurements made for both studies overlap and the relative percent difference (RPD) of the averages is 9.0%, it can be concluded that exceeding the recommended concentration for the test system by a factor of four had a minimal impact to the overall result. Therefore, the individual Kow values from both studies were considered collectively to calculate an average Kow of 47.9 with RSD% of 2.64%.

Table 1: n-Octanol/Water Partition Coefficient Log(Kow) for MTDID 37480    

 

Ratio (Octanol:Water)	Vial	Avg. Conc. in water phase (µg/mL)	Conc. in octanol phase (µg/mL)	Kow	Log Kow
0.04M Dose
1:1	1	173 (2.7%)	8840 (8.9%)	51.0
1:1	2	178 (1.9%)	9040 (6.2%)	50.8
Average				50.9
% RPD				0.42%
1:2	1	169 (5.7%)	8340 (12.5%)	49.4
1:2	2	174 (1.01%)	8400 (17.5%)	48.3
Average				48.9
% RPD				2.3%
2:1	1	183 (4.3%)	8960 (8.2%)	48.9
2:1	2	176 (0.78%)	9100 (2.4%)	51.6
Average				50.3
% RPD				5.3%
Average (0.04M)				50.0	1.7
% RSD (0.04M)				2.6%
0.01M Dose
1:1	1	49.1 (1.8%)	2190 (0.77%)	44.6
1:1	2	48.7 (0.73%)	2370 (0.65%)	48.6
Average				46.6
% RPD				8.7%
1:2	1	46.9 (3.2%)	2080 (9.7%)	44.2
1:2	2	46.9 (1.8%)	2170 (1.7%)	46.2
Average				45.2
% RPD				4.3%
2:1	1	47.9 (1.1%)	2140 (6.4%)	44.6
2:1	2	48.2 (4.5%)	2200 (2.9%)	46.1
Average				45.4
% RPD				3.4%
Average (0.01M)				45.7	1.7
% RSD (0.01M)				3.6%
Combined (0.04M and 0.01M) Average				47.9	1.7
Combined RSD% (N= 12)				2.64 %

 

 

Conclusions:

MTDID 37480 has an average measured Kow of 47.9 (RSD% = 2.64) which corresponds to a log Kow of 1.7.

Executive summary:

The n-Octanol/Water Partition Coefficient (log Kow) of  MTDID 37480 was determined according to U.S EPA guidance document OPPTS 830.7550 and OECD 107 "Partition Coefficient (n-Octanol/Water), Shake Flask Method".

Duplicate samples of MTDID 37480 were prepared in each of the three octanol/water ratios (1:1, 1:2, and 2:1). The entire volume of the two-phase system nearly filled each test vessel helping to minimize loss of material due to volatilization. The test vessels were dosed with MTDID 37480 at two dose level of 0.04M and 0.01M. All vials were then rotated 180° about their transverse axis for 100 times for five minutes to ensure proper mixing of the test system. The test vessels were centrifuged at a setting of 1000 RPM for 30 minutes to ensure a visibly clear separation of layers. Duplicate aliquots from n-octanol phase were removed first, followed by duplicate aliquots of water phase. All samples were diluted and analyzed separately using GC/MS.

Average Kow measured was 50.0 (2.5% RSD) and 45.7 (3.6% RSD) for the 0.04 M and 0.01 M studies, respectively. Both studies produced a log Kow value of 1.7. Kow values from both studies were considered collectively to calculate an average Kow of 47.9 with a RSD% of 2.64%. Log Kow for MTDID 37480 is 1.7.

This is a guideline study conducted under GLP compliance.  Therefore, it is considered reliable without restrictions.

Description of key information

The maximum achievable log Kow for C4 F-isonitrile was 4.3 ±0.2 at 24˚C under forced condition. Once in solution, C4 F-isonitrile hydrolyzed to form amide. The amide (MTDID 37480) has a measured log Kow of 1.7.

Key value for chemical safety assessment

Log Kow (Log Pow):

4.3

at the temperature of:

24 °C

Additional information

C4 F-isonitrile is a gas at ambient temperature. Once in solution, the dissolved C4 F-isonitrile hydrolyzed to form amide. Therefore, partition coefficient (log Kow) of C4 F-isonitrile and heptafluoropropylamide (MTDID 37480) were investigated.

A study was conducted to determine the log Kow of C4 F-isonitrile using method similar to U.S EPA guidance document OPPTS 830.7550 "Partition Coefficient (n-Octanol/Water), Shake Flask Method". Duplicate samples of C4 F-isonitrile were prepared in each of the three octanol/water ratios (1:1, 1:2, and 2:1). All test vessels contained 12.5 mL of headspace. All vials were then rotated 180° about their transverse axis for 100 times for five minutes, then inverted placed on an orbital shaker at ambient temperature at a setting of 50 RPM for two hours. The vials were then centrifuged at a setting of 1000 RPM for 10 minutes.  Aliquots from the headspace, aqueous and n-octanol phases were carefully removed and analyzed separately using GC/MS. Log Kow for C4 F-isonitrile was determined to be 4.3 ± 0.2 under the conditions of this study where excess C4 F-isonitrile test substance was present in the test system vials and producd an observed steady-state condition at the time when the n-octanol and water aliquots were sampled. This study was conducted similar to guideline under GLP compliance.  The study used a three-phase (gas, water, and n-octanol) test system to determine the maximum achievable log Kow for C4 F-isonitrile under forced conditions (great excess of test substance) and a short study duration to minimize the effects of hydrolysis and reaction. Therefore, it is considered reliable with acceptable restrictions.

The log Kow of MTDID 37480 was determined according to U.S EPA guidance document OPPTS 830.7550 and OECD 107 "Partition Coefficient (n-Octanol/Water), Shake Flask Method".  Duplicate samples of MTDID 37480 were prepared in each of the three octanol/water ratios (1:1, 1:2, and 2:1). The entire volume of the two-phase system nearly filled each test vessel helping to minimize loss of material due to volatilization. The test vessels were dosed with MTDID 37480 at two dose level of 0.04M and 0.01M. All vials were then rotated 180° about their transverse axis for 100 times for five minutes. The test vessels were then centrifuged at a setting of 1000 RPM for 30 minutes. Duplicate aliquots from n-octanol phase and duplicate aliquots from water phase were removed carefully for analysis separately using GC/MS. MTDID 37480 has an average measured Kow of 47.9 with a RSD% of 2.64% calculate from both the 0.04 M and 0.01 M dose levels. Log Kow for MTDID 37480 is 1.7. This is a guideline study conducted under GLP compliance. Therefore, it is considered reliable without restrictions.