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Henry's law constant
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05 December 2013 - 17 December 2013
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
other: calculation based on experimental data
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:

Test material

Details on test material:
- Name of test material (as cited in study report: L-21609
- Substance type: Mono-constituent
- Physical state: clear and colorless gas at ambient conditions

Results and discussion

Henry's Law constant H
25 900 dimensionless
23 °C
Atm. press.:
760 mm Hg

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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.