6-Amino-5-chloro-2-cyclopyrimidine-4-carboxylic acid

Water solubility

Link to relevant study record(s)

Reference

Endpoint:

water solubility

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-07-16 to 2007-08-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 105 (Water Solubility)

Version / remarks:

1995

GLP compliance:

yes (incl. QA statement)

Remarks:

Food and Consumer Product Safety Authority (WMA), Den Haag, The Netherlands / National GLP Compliance Monitoring Authority, New Delhi, India

Type of method:

flask method

Key result

Water solubility:

2.81 g/L

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 3.34 - <= 3.37

Remarks on result:

other: Solubility in Milli-Q® Water

Key result

Water solubility:

3.13 g/L

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 3.63 - <= 3.71

Remarks on result:

other: Solubility in pH 4 aqueous buffer solution

Key result

Water solubility:

4.2 g/L

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 4.36 - <= 4.37

Remarks on result:

other: Solubility in pH 7 aqueous buffer solution

Key result

Water solubility:

3.87 g/L

Incubation duration:

>= 24 - <= 72 h

Temp.:

20 °C

pH:

>= 4.29 - <= 4.33

Remarks on result:

other: Solubility in pH 9 aqueous buffer solution

Details on results:

Measured pH values are lower than the nominal buffer pH. However, the obtained results show that the water solubility of the substance is pH-dependent: the lower the pH, the lower the water solubilty.

Preliminary Test

The estimated solubility of test item in Milli-Q® water, and buffer solutions of pH 4, 7, and 9 was determined in the preliminary test. It was observed that the test item is found soluble in Milli-Q® water and buffer solution of pH 7, after making up to 100 mL.

The test item solutions in buffer solutions of pH 4 and 9 were found soluble after 24 hours. The preliminary solubility of the test item in all the media (Milli-Q® water, buffer solutions of pH 4, 7, and 9) was less than 0.01 g/L.

 

Main test

The results from the main test are presented in in the following table.

Media	Interval (Hrs.)	Water solubility (g/L) at 20 °C
		R1	R2	R3	Mean ± S.D.
Milli-Q® Water	24	2.97	2.94	2.88	2.93 ± 0.04
	48	2.71	2.82	2.70	2.74 ± 0.06
	72	2.77	2.78	2.77	2.77 ± 0.01
				Mean ± S.D.	2.81 ± 0.10
pH 4 Buffer Solution	24	3.15	3.15	3.13	3.14 ± 0.01
	48	2.86	2.90	2.86	2.87 ± 0.02
	72	3.39	3.39	3.39	3.39 ± 0.01
				Mean ± S.D.	3.13 ± 0.26
pH 7 Buffer Solution	24	4.12	4.11	4.12	4.11 ± 0.01
	48	4.16	4.14	4.11	4.13 ± 0.02
	72	4.35	4.36	4.37	4.36 ± 0.02
				Mean ± S.D.	4.20 ± 0.14
pH 9 Buffer Solution	24	3.67	3.67	3.69	3.68 ± 0.01
	48	4.01	4.00	4.00	4.00 ± 0.02
	72	3.92	3.93	3.94	3.93 ± 0.01
				Mean ± S.D.	3.87 ± 0.17

 

The results showed that the saturation of the test item in the water was achieved in the third sample (72 hours).

The mean value of water solubility was calculated based on the three samples. The variation between the last two samples was lower than the maximum allowed difference of 15% as based on the guidelines. These parameters clearly demonstrate the validity of the test conducted and the results obtained.

The result showed that overall mean value for water solubility of test item in Milli-Q® water, buffer solutions of pH 4, 7, and 9 were 2.81 ± 0.1, 3.13 ± 0.26, 4.20 ± 0.14 and 3.87 ± 0.17 g/L respectively at 20 °C.

 

The pH values for the test samples were determined on each sampling day. The details of pH values were presented in the following table.

Media	Milli-Q® Water			Buffer Solution of pH 4			Buffer Solution of pH 7			Buffer Solution of pH 9
Interval (Hrs.)	24	48	72	24	48	72	24	48	72	24	48	72
R1	3.31	3.35	3.35	3.66	3.68	3.68	4.40	4.32	4.31	4.26	4.31	4.30
R2	3.33	3.38	3.32	3.60	3.73	3.70	4.32	4.38	4.39	4.24	4.25	4.28
R3	3.37	3.39	3.38	3.63	3.71	3.69	4.38	4.36	4.37	4.39	4.30	4.31
Mean	3.34	3.37	3.35	3.63	3.71	3.69	4.37	4.36	4.36	4.33	4.29	4.30

 

Conclusions:

The water solubility at 20 °C of the substance was determined using Milli-Q water and three aqueous buffer solutions (OECD Guideline 105, flask method):
2.81 g/L (Milli-Q water; measured pH: 3.34-3.37)
3.13 g/L (pH4 aqueous buffer solution; measured pH: 3.36-3.71)
4.2 g/L (pH7 aqueous buffer solution; measured pH: 4.36-4.37)
3.87 g/L (pH9 aqueous buffer solution; measured pH: 4.29-4.33)

Description of key information

Solubility in Milli-Q® Water: 2.81 g/L at 20 °C and pH 3.34-3.37

Solubility in pH 4 aqueous buffer solution: 3.13 g/L at 20 °C and pH 3.63-3.71

Solubility in pH 7 aqueous buffer solution: 4.2 g/L at 20 °C and pH 4.36-4.37

Solubility in pH 9 aqueous buffer solution: 3.87 g/L at 20 °C and pH 4.29-4.33

(OECD Guideline 105, flask method)

Key value for chemical safety assessment

Water solubility:

4.2 g/L

at the temperature of:

20 °C

Additional information

The highest measured water solubility is selected as key information for CSA.