N-[[3,5-dichloro-2-fluoro-4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl]carbamoyl]-2,6-difluorobenzamide

Solubility in organic solvents / fat solubility

Link to relevant study record(s)

Reference

Endpoint:

solubility in organic solvents / fat solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 February 2001 - 16 March 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from the standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to valid guidelines and conducted under GLP conditions.

Qualifier:

equivalent or similar to guideline

Guideline:

other: EPA OPPTS 830.7840 (water solubility: column elution method; shake flask method)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

other: OECD 105 (water solubility)

Deviations:

no

GLP compliance:

yes

Key result

Medium:

acetone

Solubility:

425 g/L

Temp.:

19 °C

Medium:

acetonitrile

Solubility:

44.9 g/L

Temp.:

19 °C

Medium:

other: 1,2-Dichloroethane

Solubility:

20.7 g/L

Temp.:

19 °C

Medium:

ethyl acetate

Solubility:

290 g/L

Temp.:

19 °C

Medium:

other: heptane

Solubility:

0.068 g/L

Temp.:

19 °C

Medium:

methanol

Solubility:

48.9 g/L

Temp.:

19 °C

Medium:

n-octanol

Solubility:

8.1 g/L

Temp.:

19 °C

Medium:

other: p-Xylene

Solubility:

93.3 g/L

Temp.:

19 °C

Test substance stable:

not determined

Details on results:

Method Verification
Both methods of sample preparation of saturated test solutions in organic solvents were evaluated for accuracy. The recovery data indicates that the methods used for sample preparation were sufficient to determine the solubility of the test material in the samples for all solvents. Recovery ranged from 82.0 to 109.2 %.

Estimation of Solubility
The solubility observed in acetone, acetonitrile, ethyl acetate and methanol were all less than 50%. Acetonitrile, ethyl acetate, and methanol solutions prepared at 5 g (test material) in 10 mL of solvent all had test material in solution that did not dissolve. After the second addition of 5 g to the acetone aliquot, the solution turned from clear to containing excess test material that did not dissolve.

Solubility in Organic Solvents
The solubility in each solvent is presented in Table 2. The test substance was considered to be at equilibrium when the difference between the last two sampling days (48 and 72 hours) was less than 15%.

Table 2: Organic Solvent Solubility Results

Solvent	Solubility (g/L)				Solubility* (g/L)
	24 hour	48 hour	72 hour	48, 72 hour difference (%)
acetone	711.2	400.0	450.9	12.0	425
acetonitrile	30.6	45.5	44.2	2.9	44.9
1,2-dichloroethane	20.6	19.9	21.5	7.7	20.7
ethyl acetate	477.5	279.2	301.3	7.6	290
heptane	0.088	0.065	0.070	8.7	0.068
methanol	71.9	45.7	52.1	13.3	48.9
n-octanol	9.8	7.9	8.4	6.0	8.1
p-xylene	134.0	88.7	97.9	9.8	93.3

* mean of 48 and 72 hour samples.

Table 3: Density of 72 Hour Saturated Solutions

Solvent	Saturated Solvent Density (g/cm³)	Solvent Density (g/cm³)
Acetone	1.0797	0.79
Acetonitrile	0.8006	0.78
Ethyl Acetate	1.0852	0.9
Methanol	0.8272	0.79
p-Xylene	0.9234	0.86
1,2 Dichloroethane	1.2552	1.25

 

Conclusions:

Under the conditions of the test, the test material solubility in the following solvents were determined to be; acetone 425 g/L, acetonitrile 44.9 g/L, ethyl acetate 290 g/L, heptane 0.068 g/L, methanol 48.9 g/L, n-octanol 8.1 g/L, p-xylene 93.3 g/L, and 1,2-dichloroethane 20.7 g/L.

Executive summary:

The solubility of the test material in organic solvents was determined in a GLP study performed according to a method equivalent to the standardised guidelines OECD 105 and EPA OPPTS 830.7840.

The organic solvent solubility of the test material was determined using the shake-flask method. The test material was mixed with aliquots of each organic solvent, stored at 19 °C with agitation, and then assayed by HPLC. The solubility was determined in the following solvents; acetone, acetonitrile, ethyl acetate, heptane, methanol, n-octanol, p-xylene, and 1,2-dichloroethane.

Analysis was performed by HPLC/UV. An external calibration curve was prepared by analysing standard solutions of the test material, and the concentrations of the samples were determined from the calibration curve.

Under the conditions of the test, the test material solubility in the following solvents were determined to be; acetone 425 g/L, acetonitrile 44.9 g/L, ethyl acetate 290 g/L, heptane 0.068 g/L, methanol 48.9 g/L, n-octanol 8.1 g/L, p-xylene 93.3 g/L, and 1,2-dichloroethane 20.7 g/L.

Description of key information

Solvent solubilities, shake flask method, acetone 425 g/L, acetonitrile 44.9 g/L, ethyl acetate 290 g/L, heptane 0.068 g/L, methanol 48.9 g/L, n-octanol 8.1 g/L, p-xylene 93.3 g/L, and 1,2-dichloroethane 20.7 g/L. OECD 105, EPA OPPTS 830.7840, Busse 2001

Additional information

The solubility of the test material in organic solvents was determined in a GLP study performed using a method equivalent to the standardised guidelines OECD 105 and EPA OPPTS 830.7840. The study was assigned a reliability score of 1, reliable without restrictions, in line with the principles of Klimisch et al. (1997).

The organic solvent solubility of the test material was determined using the shake-flask method. The test material was mixed with aliquots of each organic solvent, stored at 19 °C with agitation, and then assayed by HPLC. The solubility was determined in the following solvents; acetone, acetonitrile, ethyl acetate, heptane, methanol, n-octanol, p-xylene, and 1,2-dichloroethane.

Analysis was performed by HPLC/UV. An external calibration curve was prepared by analysing standard solutions of the test material, and the concentrations of the samples were determined from the calibration curve.

Under the conditions of the test, the test material solubility in the following solvents were determined to be; acetone 425 g/L, acetonitrile 44.9 g/L, ethyl acetate 290 g/L, heptane 0.068 g/L, methanol 48.9 g/L, n-octanol 8.1 g/L, p-xylene 93.3 g/L, and 1,2-dichloroethane 20.7 g/L.