N-amidinosarcosine

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15-16 Decemeber 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

GLP compliance:

yes

Type of method:

flask method

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

< -2

Temp.:

20 °C

Remarks on result:

other: pH value not reported.

Details on results:

The mean value of the log Kow (-3.17) is below the applicability range of -2 to 4 of the flask method. Therefore, the log Kow of creatine monohydrate is set to < -2.

The system suitability test prefomred prior to the HPLC analysis has met the acceptance criteria.

Table 1: Amount of creatine monohydrate in water and n-octanol

Sample No.	Amount of		Nominal amount of test substance [mg]	Actual amount of test substance^1) 2)after equilibrium in		Recovery as % of used amount
	Aqueous stock solution [ml]	n-octanol [ml]		Water [mg]	n-octanol [mg]
1-1	50	50	10.054	10.012	0.007	99.65
1-2	50	50	10.054	10.051	0.009	100.06
2-1	50	100	10.054	10.036	0.011	99.93
2-2	50	100	10.054	10.067	0.013	100.26
3-1	100	50	20.108	20.070	0.007	99.85
3-2	100	50	20.108	20.103	0.006	100.00
				Mean recovery:		99.96

¹⁾Mean value of 2 injections

²⁾Calculated with the concentrations listed in table 2

Table 2: Concentration of creatine monohydrate, partition coefficients

Sample No.	Actual amount of creatine monohydrate in		Kow Cn-octanol/ Cwater	Log Kow
	n-octanol [mg/L]	Water [mg/L]
1-1	0.144	200.24	0.000719	-3.14
1-2	0.183	201.03	0.000910	-3.04
2-1	0.113	200.72	0.000563	-3.25
2-2	0.130	201.34	0.000646	-3.19
3-1	0.131	200.70	0.000653	-3.19
3-2	0.119	201.03	0.000592	-3.23
		Mean:	0.000681	-3.17

Conclusions:

The log Kow for creatine monohydrate is < -2.

Executive summary:

In a GLP guideline study according o EU method A.8 the n-octanol/ water partition coefficient of creatine monohydrate (Creapure TM) was determined.

Creatine monohydrate is almost insoluble in n-octanol. Only traces of the test substance could be found in the organic phase, but nearly all of the amount of the test substance could be found in the aqueous phase; the recovery rate was 100 %. The resulting log Kow value of ~ -3.17 is beyond the application range of the used flask shaking method (log Kow range: -2 to 4). Therefore, the log Kow for creatine monohydrate was set to < -2.

In the course of this examination no observations were made which might have influenced the intergrity of the study.

Justification for read-across:

Due to the known, very low solubility of creatine monohydrate in octanol the stock solution was prepared in water pre-saturated with octanol. Subsequently, the aqueous stock solution was equilibrated with octanol. After separation of the two phases (→ centrifugation), the concentration of creatine (not creatine monohydrate!) in both solvents was determined using HPLC.

In addition, the water that is contained in creatine monohydrate is not chemically bound and does not have any influence on the structure of the substance and does not influence the partioning behavior of creatine monohydrate. When dissolved in water there is no chemical difference between creatine and creatine monohydrate as the water crystal water is released from the creatine lattice.

Description of key information

In a GLP guideline study according to EU method A.8 the n-octanol/ water partition coefficient of creatine monohydrate

(Creapure TM) was determined to be < -2.

Key value for chemical safety assessment

Log Kow (Log Pow):

-2

at the temperature of:

20 °C

Additional information

In a GLP guideline study according to EU method A.8 the n-octanol/ water partition coefficient of creatine monohydrate (Creapure TM) was determined. This information is used for read-across to creatine.

Creatine monohydrate is almost insoluble in n-octanol. Only traces of the test substance could be found in the organic phase, but nearly all of the amount of the test substance could be found in the aqueous phase; the recovery rate was 100 %. The resulting log Kow value of ~ -3.17 is beyond the application range of the used flask shaking method (log Kow range: -2 to 4). Therefore, the log Kow for creatine monohydrate was set to < -2. The same valued is used in the risk assessment of creatine.