4-morpholinopropanesulphonic acid

Partition coefficient

Administrative data

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 November - 6 November 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP - guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method)

Deviations:

yes

Remarks:

Not all reference items had purity “for analytical purposes”: Since all reference items gave single peaks in the HPLC runs and no quantitative determinations were demanded,the deviation is assumed to have had no influence on the outcome of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient)

Deviations:

yes

Remarks:

Not all reference items had purity “for analytical purposes”: Since all reference items gave single peaks in the HPLC runs and no quantitative determinations were demanded,the deviation is assumed to have had no influence on the outcome of the study.

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Test material

Test material information

Constituent 1

Reference substance name:

4-morpholinopropanesulphonic acid

EC Number:

214-478-5

EC Name:

4-morpholinopropanesulphonic acid

Cas Number:

1132-61-2

Molecular formula:

C7H15NO4S

IUPAC Name:

3-morpholin-4-ylpropane-1-sulfonic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report) : MOPS High Purity
- Substance type : pure substance
- Physical state : white powder
- Analytical purity : 100,3%
- Purity test date : not stated
- Lot/batch No. : 1190567/006
- Expiration date of the lot/batch : 31 August 2004
- Storage condition of test material : The test item was stored in a closed polyethylene vessel at room temperature .

Study design

Analytical method:

high-performance liquid chromatography

Results and discussion

Partition coefficient

Type:

log Pow

Partition coefficient:

< 2

Temp.:

22 °C

pH:

7.3

Details on results:

Variations in the retention times of reference items and test item are very small. Therefore a stable configuration of the HPLC-column can be assumed.
The correlation log K/log Pow is not perfect. This might be due to the differences in the chemical structure of the reference items. Since no suitable reference items (with a structure similar to the structure of the test item and known Pow) were available, this can not be helped.
Because of the log Pow < 0, the HPLC-Method is not applicable.
Calculations of the log Pow (based an the structure of the test item) gave a mean value of - 2.14. Therefore, the Shake flask method is not applicable, either.
Since classification of chemicals due to their log Pow applies to chemicals with high log Pow (> 3,0; representing bioaccumulative potential), a calculation of the log Pow, is sufficient for notification purposes because experimental determination gave a log Pow < 0.

Any other information on results incl. tables

Findings

Data : measured on 5 November 2003

	log Pow	RT 1	RT 2	RT 3	RT 4	RT 5	RT 6
Thiourea	k.A.	2	2	2	2	2	2
Aniline	0,9	2,84	2,84	2,84	2,84	2,84	2,84
Phenole	1,5	3,17	3,18	3,18	3,17	3,17	3,17
Nitrobenzene	1,9	4,64	4,64	4,64	4,64	4,64	4,64
Benzene	2,1	6,71	6,71	6,71	6,71	6,71	6,71
Trichloroethene	2,4	9,4	9,4	9,41	9,42	9,41	9,42
Toluene	2,7	10,71	10,71	10,71	10,72	10,71	10,71
Styrene	2,95	11,86	11,86	11,86	11,87	11,86	11,86

Calculations

	log Pow	RT mean	sd	k	log(k)
Thiourea	k.A.	2,000	0,000	0
Aniline	0,9	2,840	0,000	0,42	-0,377
Phenole	1,5	3,173	0,005	0,58667	-0,232
Nitrobenzene	1,9	4,640	0,000	1,32	0,1206
Benzene	2,1	6,710	0,000	2,355	0,372
Trichloroethene	2,4	9,410	0,009	3,705	0,5688
Toluene	2,7	10,712	0,004	4,35583	0,6391
Styrene	2,95	11,862	0,004	4,93083	0,6929

Results :

Dead time is 1,642 ± 0,000 minutes, with RSD 0,0%.

The RSD of the retention times of the reference items lay all below 0,5 %.

Equation of the regression : log(k) = 0,59055 * logP_OW – 0,96407 with a correlation of r² = 0,9476.

Parameter	Value
slope	0,59055
intercept	-0,96407

Test Item MOPS High Purity

	RT	k	log(k)	log Pow
measurement 1	1,642	-0,179	--	< 0
measurement 2	1,642	-0,179	--	< 0
measurement 3
mean	1,642			< 0
standard deviation	0,000

Calculation of logP_ow from Experimental Value

logP_OW is calculated from the capacity factor as follows:

logP_OW = (log(k) + 0,96407) / 0,59055

Log P_OW of the test item MOPS High Purity is < 0

Calculation of logP_ow from Structural Formula

Calculations of the logPow (based on the stucture of the test item) gave -1,69 from "IA LogP" and -2,58 from KowWIN (SYRRES) , mean -2,14 . Therefore , the shake flask method is not applicable , either. Both methods use fragment coefficients for the calculation .

Applicant's summary and conclusion

Conclusions:

The study report describes a reliable GLP guideline study for the determination of the partition coefficient (octanol-water) of the test substance. The GLP status is confirmed with a certificate, the test was performed according to OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method) and EU Method A.8 (Partition Coefficient) with the deviation from the guideline, that not all reference items had purity “for analytical purposes”: Since all reference items gave single peaks in the HPLC runs and no quantitative determinations were demanded, the deviation is assumed to have had no influence on the outcome of the study.
log Pow of MOPS High Purity can be stated as < 2,0.

Executive summary:

The study report describes a reliable GLP guideline study for the determination of the partition coefficient (octanol-water) of the test substance. The GLP status is confirmed with a certificate, the test was performed according to OECD Guideline 117 (Partition Coefficient (n-octanol / water), HPLC Method) and EU Method A.8 (Partition Coefficient) with the deviation from the guideline, that not all reference items had purity “for analytical purposes”: Since all reference items gave single peaks in the HPLC runs and no quantitative determinations were demanded, the deviation is assumed to have had no influence on the outcome of the study. The study was performed using a HPLC with a C18 column. Eight reference items with different retention times were used to produce a calibration curve, since retention time on hydrophobic columns and Pow are correlated. The reference items were chosen an behalf of the calculated log Pow provided by the sponsor. First, a solution of the reference items was analysed three times with HPLC, then a solution of the test item (two times) and finally three more times the solution with the references. For each reference item, the capacity factor K was calculated from the retention time of thiourea and the retention time of the respective reference item. A calibration function was determined using the literature values for Pow of the references items in the six determinations (Log K versus Log Pow, linear fit). The chromatogram of the test item gave one peak (RT = 1.642 min). With the help of the calibration, the Log Pow could be determined as < 0 . The test item MOPS High Purity has a log Pow of < 0. Therefore, the HPLC method is not applicable. Calculation of the log Pow gave a value of -2,14; thus the Shake Flask Method is not applicable, either.

log Pow of MOPS High Purity can be stated as < 2,0.