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

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2007-08-31 to 2007-09-19

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 107 (Partition Coefficient (n-octanol / water), Shake Flask Method)

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

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

-1.12

Temp.:

20 °C

Remarks on result:

other: pH not reported

Remarks:

n-Octanol / Milli-Q water partition coefficient

Key result

Type:

log Pow

Partition coefficient:

-1.01

Temp.:

20 °C

Remarks on result:

other: pH not reported

Remarks:

n-Octanol / aqueous buffer pH4 partition coefficient

Key result

Type:

log Pow

Partition coefficient:

-2.48

Temp.:

20 °C

Remarks on result:

other: pH not reported

Remarks:

n-Octanol / aqueous buffer pH7 partition coefficient

Details on results:

The n-Octanol / aqueous buffer pH9 partition coefficient could not be calculated because the test item was not detected in the n-octanol phase of octanol / buffer pH 9.0 at 20 ± 1 °C due to its high water solubility at alkaline pH.

The concentration of the test item stock solutions prepared in n-octanol presaturated for the tests with Milli-Q water and pH 4.0, 7.0, and 9.0 aqueous buffer solutions were 72.28, 70.66, 70.29, and 70.56 µg/mL, respectively.

The mean partition coefficient (log Pow) of the test item was:

-1.07 ± 0.00, -1.17 ± 0.01, and -1.12 ± 0.01 for the octanol-Milli-Q water ratio of 1:1, 1:2, and 2:1 respectively at 20 ± 1 °C.

-1.01 ± 0.01, -1.02 ± 0.01, and -1.01 ± 0.00 for the octanol-pH 4.0 aqueous buffer solution ratio of 1:1, 1:2, and 2:1 respectively at 20 ± 1 °C.

-2.48 ± 0.01 and -2.48 ± 0.03 for the octanol-pH 7.0 aqueous buffer solution ratio of 1:1 and 2:1 respectively at 20 ± 1 °C while the test item was not detected in octanol phase of 1:2 ratio.

The test item was not detected in n-octanol phase of 1:1, 1:2, and 2:1 ratios of octanol-pH 9.0 aqueous buffer solution at 20 ± 1 °C.

 

The overall mean partition coefficient (log Pow) of the test item at 20 ± 1 °C were -1.12 ± 0.04, -1.01 ± 0.01, and -2.48 ± 0.02 for the n-octonal-Milli-Q water and n-octonal-aqueous buffers of pH 4.0 and 7.0, respectively. The test item was not detected in the n-octanol phase of 1:1, 1:2, and 2:1 ratios of octanol-buffer pH 9.0 at 20 ± 1 °C due to its high water solubility at alkaline pH.

 

The detailed results of the log Pow determination are given in the following tables.

 

Test results: partition coefficient n-Octanol / Milli-Q water

n-Octanol to Milli-Q water ratio	Replication (R)	Volume of (mL)		Test item concentration (µg/mL)		Amount (µg) of test item				Log Pow	Mean ± S.D
		n-Octanol	Milli-Q water	n-Octanol	Milli-Q water	n-Octanol	Milli-Q water	Total	Mean ± S.D
1:1	R1	50	50	5.50	64.97	275	3249	3524	3528 ± 5.66	-1.07	-1.07 ± 0.00
1:1	R2	50	50	5.50	65.13	275	3257	3532		-1.07
1:2	R1	50	100	2.29	34.25	115	3425	3540	3543 ± 4.24	-1.17	-1.17 ± 0.01
1:2	R2	50	100	2.37	34.27	119	3427	3546		-1.16
2:1	R1	100	50	4.71	61.72	471	3086	3557	3537 ± 28.99	-1.12	-1.12 ± 0.01
2:1	R2	100	50	4.71	60.89	471	3045	3516		-1.11

 

Overall log Pow mean ± S.D.: -1.12 ± 0.04

 

 

Test results: partition coefficient n-Octanol / pH 4.0 aqueous buffer solution

n-Octanol to Buffer ratio	Replication (R)	Volume of (mL)		Test item concentration (µg/mL)		Amount (µg) of test item				Log Pow	Mean ± S.D
		n-Octanol	Buffer	n-Octanol	Buffer	n-Octanol	Buffer	Total	Mean ± S.D
1:1	R1	50	50	6.30	63.05	315	3153	3468	3482 ± 19.80	-1.00	-1.01 ± 0.01
1:1	R2	50	50	6.14	63.77	307	3189	3496		-1.02
1:2	R1	50	100	3.28	33.20	164	3320	3484	3526 ± 58.69	-1.01	-1.02 ± 0.01
1:2	R2	50	100	3.25	34.04	163	3404	3567		-1.02
2:1	R1	100	50	5.77	59.48	577	2974	3551	3528 ± 33.23	-1.01	-1.01 ± 0.00
2:1	R2	100	50	5.74	58.59	574	2930	3504		-1.01

 

Overall log Pow mean ± S.D.: -1.01 ± 0.01

 

 

Test results: partition coefficient n-Octanol / pH 7.0 aqueous buffer solution

n-Octanol to Buffer ratio	Replication (R)	Volume of (mL)		Test item concentration (µg/mL)		Amount (µg) of test item				Log Pow	Mean ± S.D
		n-Octanol	Buffer	n-Octanol	Buffer	n-Octanol	Buffer	Total	Mean ± S.D
1:1	R1	50	50	0.23	70.62	12	3531	3543	3534 ± 12.73	-2.49	-2.48 ± 0.01
1:1	R2	50	50	0.24	70.26	12	3513	3525		-2.47
1:2	R1	50	100	-	34.59	-	3459	3459	3468 ± 12.02	-	-
1:2	R2	50	100	-	34.76	-	3476	3476		-
2:1	R1	100	50	0.22	69.46	22	3473	3495	3491 ± 5.66	-2.50	-2.48 ± 0.03
2:1	R2	100	50	0.24	69.26	24	3463	3487		-2.46

 

Overall log Pow mean ± S.D.: -2.48 ± 0.02

 

 

Test results: partition coefficient n-Octanol / pH 9.0 aqueous buffer solution

n-Octanol to Buffer ratio	Replication (R)	Volume of (mL)		Test item concentration (µg/mL)		Amount (µg) of test item				Log Pow	Mean ± S.D
		n-Octanol	Buffer	n-Octanol	Buffer	n-Octanol	Buffer	Total	Mean ± S.D
1:1	R1	50	50	-	68.24	-	3412	3412	3415 ± 4.24	-	-
1:1	R2	50	50	-	68.36	-	3418	3418		-
1:2	R1	50	100	-	33.05	-	3305	3305	3314 ± 12.02	-	-
1:2	R2	50	100	-	33.22	-	3322	3322		-
2:1	R1	100	50	-	67.55	-	3378	3378	3376 ± 3.54	-	-
2:1	R2	100	50	-	67.45	-	3373	3373		-

 

The test item was not detected in n-octanol phase of 1:1, 1:2 and 2:2 ratios hence, log Pow values were not calculated.

Conclusions:

The octanol / water partition coefficient at 20 °C of the substance was determined using Milli-Q water and three aqueous buffer solutions (OECD Guideline 107, flask method):
-1.12 (octanol / Milli-Q water; pH of the solution not measured)
-1.01 (octanol / aqueous buffer pH4; pH of the solution not measured)
-2.48 (octanol / aqueous buffer pH7; pH of the solution not measured)
The n-Octanol / aqueous buffer pH9 partition coefficient could not be calculated because the test item was not detected in the n-octanol phase of octanol / buffer pH 9.0 at 20 ± 1 °C due to its high water solubility at alkaline pH.

Description of key information

log Pow = -1.12 at 20 °C in Milli-Q water

log Pow = -1.01 at 20 °C in pH 4.0 aqueous buffer solution

log Pow = -2.48 at 20 °C in pH 7.0 aqueous buffer solution

Key value for chemical safety assessment

Log Kow (Log Pow):

-1.12

at the temperature of:

20 °C

Additional information

A further measurement using a pH 9.0 aqueous buffer solution was attempted. In this case, the test item was not detected in the n-octanol phase and the n-octanol / aqueous buffer pH9 partition coefficient could not be calculated.