Registration Dossier

Administrative data

Endpoint:
Henry's law constant
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 28 2013 - September 19 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
This experiment followed an ESA-developed protocol and the two measurements were done under GLP, but there is no guideline for HLC experiments. The result is not a calculation, but is the proper definition of HLC (vapor phase concentration over a water solution divided by the concentration in that solution).
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): MV 31
- Substance type: pure active substance
- Physical state: Colorless, clear liquid at room temperature
- Analytical purity: 97.6%
- Expiration date of the lot/batch: 01 May 2018

Results and discussion

Henry's Law constant H
H:
19 300 dimensionless
Temp.:
23 °C
Atm. press.:
760 mm Hg

Any other information on results incl. tables

Test conducted at ambient temperature. Henry's Law constant (HLC) result is reported as a dimensionless ratio of headspace concentration of MV 31 over aqueous phase concentration. Log HLC values measured for Time Point 3 (day 7) were not usable due to a preparation problem. The headspace aliquot results for multiple vials were zero due to a plugged syringe needle. The data from Time Point 3 is not included in the final average calculation for the HLC of MV 31. Time Points 1, 2, and 4, representing equilibration durations of 5, 6, and 8 days, respectively, are reported (Table 3). The average Henry's Law constant for MV 31 was 19300, with %RSD of 13% (Table 1). The Henry's Law constant expressed as log HLC is 4.3, with %RSD of 1.4% (Table 2).

Table 1: Summary of Henry’s Law Constant (HLC) for MV 31

 

Ratio

(Headspace: Aqueous)

Replicate

 

Time point 1

(Five days)

 

Time point 2

(Six days)

 

Time point 4*

(Eight days)

70 %

Headspace

1

19400

22300

21400

2

19200

21500

20500

Average

19300

21900

21000

%RPD

1.0

3.7

4.3

50 %

Headspace

1

18400

21700

17500

2

18700

20100

20500

Average

18600

20900

19000

%RPD

1.6

7.7

16

30 %

Headspace

1

12600

19300

16900

2

15800

21500

20300

Average

14200

20400

18600

%RPD

23

11

18

Intra-Time Point Average

% RSD

17400

15

21100

5.3

19500

9.5

Overall Average

%RSD

19300

13

 ·       Time Point 3 was not included in the calculation for the HLC due to a preparation error.

Table 2: Summary of Log (HLC) for MV 31

 

Ratio

(Headspace: Aqueous)

Replicate

 

Time point 1

(Five days)

 

Time point 2

(Six days)

 

Time point 4*

(Eight days)

70 %

Headspace

1

4.3

4.3

4.3

2

4.3

4.3

4.3

Average

4.3

4.3

4.3

%RPD

0.11

0.37

0.43

50 %

Headspace

1

4.3

4.3

4.2

2

4.3

4.3

4.3

Average

4.3

4.3

4.3

%RPD

0.16

0.77

1.6

30 %

Headspace

1

4.1

4.3

4.2

2

4.2

4.3

4.3

Average

4.1

4.3

4.3

%RPD

2.4

1.1

1.9

Intra-Day Average

% RSD

4.2

1.7

4.3

0.55

4.3

0.99

Overall Average

%RSD

4.3

1.4

 ·       Time Point 3 was not included in the calculation for the HLC due to a preparation erro

Table 3: Individual results of Henry’s Law Constant (HLC) for MV 31

Time point 1, 70% Headspace

MV 31

Water conc. (ng/mL)

MV 31 Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

3.63

72300

aliquot 2

3.64

68400

Average

3.63

70300

19400

4.3

% RPD

0.39

5.6

Replicate 2

aliquot 1

3.42

69100

aliquot 2

3.69

67500

Average

3.56

68300

19200

4.3

% RPD

7.7

2.4

Time point 1, 50% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

3.36

63800

aliquot 2

3.22

57700

Average

3.29

60700

18400

4.3

% RPD

4.1

10

Replicate 2

aliquot 1

3.13

55500

aliquot 2

2.85

56100

Average

2.99

55800

18700

4.3

% RPD

9.3

0.94

Time point 1, 30% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

2.92

30900

aliquot 2

2.67

39700

Average

2.80

35300

12600

4.1

% RPD

9.2

25

Replicate 2

aliquot 1

3.15

46400

aliquot 2

2.90

49600

Average

3.03

48000

15800

4.2

% RPD

8.3

6.8

 

 

Time point 2, 70% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

2.91

65900

aliquot 2

2.91

63700

Average

2.91

64800

22300

4.3

% RPD

0.095

3.3

Replicate 2

aliquot 1

3.01

65500

aliquot 2

2.89

61000

Average

2.95

63300

21500

4.3

% RPD

4.1

7.2

Time point 2, 50% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

3.23

68000

aliquot 2

2.95

66400

Average

3.09

67200

21700

4.3

% RPD

8.9

2.4

Replicate 2

aliquot 1

3.40

68500

aliquot 2

3.17

63900

Average

3.29

66200

20100

4.3

% RPD

7.1

6.9

Time point 2, 30% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

3.13

60500

aliquot 2

3.12

59800

Average

3.12

60200

19300

4.3

% RPD

0.48

1.2

Replicate 2

aliquot 1

3.10

30000(1)

aliquot 2

2.90

64400

Average

3.00

64400

21500

4.3

% RPD

6.6

NA

(1) Not used in average calculation. The value was statistically determined to be an outlier at a 95%

confidence level in relation to all headspace aliquots from TP2, 30% headspace.

 

 

Time point 4, 70% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

3.59

77500

aliquot 2

3.51

74000

Average

3.55

75800

21400

4.3

% RPD

2.2

4.7

Replicate 2

aliquot 1

3.50

75400

aliquot 2

3.78

74200

Average

3.64

74800

20500

4.3

% RPD

7.6

1.7

Time point 4, 50% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

4.19

68400

aliquot 2

3.71

70200

Average

3.95

69300

17500

4.2

% RPD

12

2.6

Replicate 2

aliquot 1

3.93

76100

aliquot 2

3.35

73200

Average

3.64

74700

20500

4.3

% RPD

16

4.0

Time point 4, 30% Headspace

MV 31

Water conc. (ng/mL)

MV 31

Headspace conc. (ng/mL)

HLC

log HLC

Replicate 1

aliquot 1

3.49

54900

aliquot 2

3.35

60600

Average

3.42

57700

16900

4.2

% RPD

4.2

9.9

Replicate 2

aliquot 1

3.64

75100

aliquot 2

3.62

72600

Average

3.63

73800

20300

4.3

% RPD

0.53

3.5

Applicant's summary and conclusion

Conclusions:
The Henry's Law constant (HLC) for MV 31 was determined to be 19300 at 23 °C based on measured concentrations in the headspace phase and water phase. The average log HLC was 4.3.
Executive summary:

The Henry's Law constant of MV 31 was determined by the ratio of headspace concentration over aqueous phase concentration.

Duplicate test vessels were filled with water and dosed with MV 31 gas at three headspace:water ratios (70%, 50% and 30%). The vials were incubated for 5, 6, and 8 days at ambient temperature. Both the headspace and the water phase for each vial were sampled and analyzed in duplicates using gas chromatography/mass spectrometry (GC/MS). The average measured gas phase and water phase concentrations were used to calculate Henry's Law constant for MV 31 for each test vessel.

The average Henry's Law constant for MV 31 was 19300 at 23 °C.

The Henry's Law constant expressed as log HLC is 4.3 at 23 °C. This study was conducted under GLP compliance with accepted method. Therefore, it is considered reliable without restrictions.