Propanamide, N-[4-(2,4-dihydroxyphenyl)-2-thiazolyl]-2-methyl-

Water solubility

Administrative data

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 - 28 Feb 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.6 (Water Solubility)

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesamt Umwelt, Wasserwirtschaft und Gewerbeaufsicht, Mainz, Germany

Type of method:

flask method

Test material

Test material information

Constituent 1

Reference substance name:

N-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpropanamide

EC Number:

807-621-3

Cas Number:

1428450-95-6

Molecular formula:

C13H14N2O3S

IUPAC Name:

N-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpropanamide

Test material form:

solid: particulate/powder

Results and discussion

Water solubility

Water solubility 1

Water solubility:

11.82 mg/L

Temp.:

10.5 °C

pH:

5.88

Water solubility 2

Key result

Water solubility:

19.9 mg/L

Conc. based on:

test mat.

Temp.:

20 °C

pH:

5.89

Water solubility 3

Water solubility:

28.79 mg/L

Temp.:

29.5 °C

pH:

5.99

Any other information on results incl. tables

The data which was acquired for temperature dependency of water solubility is presented in the following table:

Flask	Temperature / °C	Concentration test item / mg/L	Difference to other sample /%
KS	4.9	11.38
RT	19.2	16.69	49.13

Because the difference between the measured concentrations of the two flasks was > 3%/°C (49.13 %/14.3 °C), the main study was performed at 10 °C, 20 °C and 30 °C.

Equilibration at 10 °C

Day	Flask	Temperature /°C	pH	Measured values / mg/L	Difference to previous sample /%
1	7A	10.5	6	11.06	--
2	7B	10.5	6	11.12	+0.6
3	7C	10.5	6	11.29	+1.5
4	7C	10.5	5.76	11.09	-1.7

After the analysis of the sample of day 4, the plateau was considered as reached and flasks 8 – 12 were sampled.

Equilibration at 20 °C

Day	Flask	Temperature /°C	pH	Measured values / mg/L	Difference to previous sample /%
1	1A	20	5.81	19.18	--
2	1B	20	5.71	18.99	-1.0
3	1C	20	5.70	19.16	+0.9

After the analysis of the sample of day 3, the plateau was considered as reached and flasks 2 – 6 were sampled.

Equilibration at 30 °C

Day	Flask	Temperature /°C	pH	Measured values / mg/L	Difference to previous sample /%
1	13A	29.5	5.64	29.15	--
2	13B	29.5	5.76	29.29	+0.5
3	13C	29.5	5.80	29.01	-1.0

After the analysis of the sample of day 3, the plateau was considered as reached and flask 14 -18 were sampled.

Flask No.	Nominal concentration / mg/L	Temperature / °C	pH	Concentration / mg/L		Mean concentration / mg/L
1A	200	20.0		19.15	19.18
				19.22
1B	200	20.0		19.01	18.99
				18.96
1C	200	20.0	5.81	19.19	19.16
				19.13
2	400	20.0	5.71	19.71	19.71
				19.72
3	600	20.0	5.70	19.95	19.94
				19.93
4	800	20.0	6.00	19.74	19.73
				19.72
5	1000	20.0	5.83	20.18	20.25
				20.31
6	1200	20.0	6.02	20.66	20.62
				20.59
7C	200	10.5	5.76	11.10	11.09
				11.09
8	400	10.5	5.94	12.10	12.09
				12.07
9	600	10.5	6.00	11.64	11.64
				11.63
10	800	10.5	5.77	12.00	12.02
				12.05
11	1000	10.5	5.88	12.03	12.02
				12.01
12	1200	10.5	5.91	12.05	12.03
				12.02
13A	200	29.5	5.64	29.14	29.15
				29.16
13B	200	29.5	5.76	29.30	29.29
				29.28
13C	200	29.5	5.8	29.02	29.01
				29.01
14	400	29.5	6.00	28.94	28.95
				28.96
15	600	29.5	5.97	28.98	28.97
				28.95
16	800	29.5	6.14	28.45	28.44
				28.44
17	1000	29.5	6.31	28.27	28.28
				28.29
18	1200	29.5	6.20	28.18	28.21
				28.24

 

20 °C: A mean concentration of 19.90 mg/L with a standard deviation of 0.46 mg/L was calculated, giving a relative standard deviation of 2.30 %.

10 °C: A mean concentration of 11.82 mg/L with a standard deviation of 0.36 mg/L was calculated, giving a relative standard deviation of 3.01 %.

30 °C: A mean concentration of 28.79 mg/L with a standard deviation of 0.39 mg/L was calculated, giving a relative standard deviation of 1.35 %.

 

Temperature /°C	Mean pH	Mean concentration /mg/L	Standard deviation /mg/L	Relative standard deviation /%
10.5	5.88	11.85	0.36	3.01
20.0	5.89	19.90	0.46	2.30
29.5	5.99	28.79	0.39	1.35

 

The water solubility of the test item was determined from the measured concentrations of N-[4-(2,4-dihydroxyphenyl)thiazol-2-yl]isobutyramide in the filtrated test solutions. Due to the observed temperature dependence of solubility (3.44 %/°C), the water solubility was tested at temperatures 10 °C, 20 °C and 30 °C as required by the EU A.6 guideline.

Equilibration time can be considered as approx. 3 days at 20 °C and 30 °C and 4 days at 10 °C, as the values which were measured on the following consecutive days did not give significantly different values.

All replicates showed good correspondence. The standard deviations of the samples which were used for the calculation of water solubility (at plateau) were in a range of 0.36 – 0.46 mg/L, corresponding to relative standard deviations of 1.35 – 3.01 %.

The test item did not show dependence of solubility on nominal concentrations. Also, pH of the solutions was not dependent on nominal concentration of the test item.

No observations arousing doubts concerning the accuracy of the results and the validity of the study were made.

Applicant's summary and conclusion

Conclusions:

N-[4-(2,4-Dihydroxyphenyl)-2-thiazolyl]-2-methylpropanamide has a water solubility of 19.9 mg/l at 20°C

Executive summary:

N-[4-(2,4-Dihydroxyphenyl)-2-thiazolyl]-2-methylpropanamide has a water solubility of 19.9 mg/l at 20°C