4,4-dimethyloxazolidine

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 November - 5 November 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - HPLC Method)

Version / remarks:

Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to
Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration,
Evaluation, Authorisation and Restriction of Chemicals (REACH)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

April 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Remarks:

with UV detection

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Lot no.:MA20190405
Storage: 2–8 °C, protected from light

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

ca. -0.92 - <= 1.11

Temp.:

25 °C

pH:

9

Remarks on result:

other: Mean of two determinations. The log Pow is given as a range as the test item is a mixture. "Ca." was inserted to meet the entry requirements. The real lower value is <= -0.92. Range <= -0.92 to 1.11

Details on results:

The dead time was determined to be 1.525 min.

Two determinations of the log Pow value of the test item were conducted by injecting a mixed solution of all reference items as well as the single test item solution twice using a borate buffered system at pH 9.0.

The test item is a mixture, and eight test item related peaks were found in the respective chromatograms used for determination of the log Pow values. Based on the retention times of these peaks, mean log Pow values were determined including their 95% confidence interval as well as their mean area% content (see corresponding table in any other information on results incl. tables).

The retention times of the first two test item peaks in both injections were shorter or about equal to the one for thiourea, which was used as dead time marker. An extrapolation based on the regression data obtained by the injection of reference items was not possible for the first peak and yielded far too low results in the case of the second peak. Therefore, the log Pow of these two peaks was estimated based on the log Pow value of thiourea, which corresponds to -0.92.

Mean log Pow values of the different test item peaks including their 95% confidence interval as well as their mean area% content:

Test item peak	Mean log Pow	95% confidence interval	Mean area%
No. 1	<=-0.92	Not applicable	0.5
No. 2	ca. -0.92	Not applicable	68.2
No. 3	-0.35	-0.85 to 0.14	16.0
No. 4	0.17	-0.24 to 0.58	6.7
No. 5	0.41	0.04 to 0.79	4.1
No. 6	0.62	0.28 to 0.97	1.3
No. 7	0.80	0.47 to 1.12	1.9
No. 8	1.11	0.81 to 1.40	1.5

Discussion of test item composition based on obtained test item chromatograms
Comparing the test item composition as given in the certificate of analysis with the chromatograms obtained in this study, more than the three expected peaks have been found. This discrepancy most likely results from the difference of analytical equipment used. For the certificate of analysis, gas chromatography has been applied, which is a very reasonable choice considering the test item main component structure, whereas in this study, HPLC had to be used based on the scientific principles of the OECD 117 guideline. It is therefore very likely, that the additional peaks found in this study correspond to test item impurities, which are overexpressed regarding their area% content as determined by HPLC with UV detection in comparison with i.e. the test item main component, whose UV absorption capacity is supposedly quite low based on its chemical structure.

Additional peak in high concentrated test item solutions
An additional peak with a retention time of about 10 min was found in the two test item injections made with a concentration of about 1400 and 700 mg/l, which were used to assign test item related peaks in comparison with the blank solvent. Its presence in the two injections used for the determination of the log Pow values, which were performed with a test item concentration of 143 mg/l was below the limit of detection as it was in the range of the baseline fluctuations. The retention time of about 10 min corresponds to a log Pow of about 3.0 with a mean area% content of 0.1.

Conclusions:

The HPLC method was applied for the determination of the log Pow. The log Pow range obtained for the test item 4,4-dimethyloxazolidine (CAS no. 51200-87-4) at pH 9.0 and 25 °C, calculated as the mean of two determinations, is <=-0.92 to 1.11.

Executive summary:

The partition coefficient between octanol and water (log Pow) of the test item 4,4-dimethyloxazolidine (CAS no. 51200-87-4) was determined according to the OECD guideline 117. This determination is based upon a regression analysis of the log Pow values of reference items against their respective retention times as determined by HPLC analysis.

The following reference items were used: caffeine, 4-acetylpyridine, acetanilide, acetophenone, methyl benzoate, benzophenone and benzyl benzoate. This set of reference items yielded a calibration with log Pow values ranging from -0.07 to 4.0. The dead time of the HPLC system was determined with thiourea.

Two determinations of the log Pow value of the test item were conducted using a borate buffered system at pH 9.0 by injecting a mixed solution of all reference items as well as the single test item solution twice.

The test item is a mixture, and eight test item related peaks were found in the respective chromatograms used for determination of the log Pow values. Based on the retention times of these peaks, the following log Pow values were determined including their 95% confidence interval as well as their mean area% content:

Test item peak	Mean log Pow	95% confidence interval	Mean area%
No. 1	<=-0.92	Not applicable	0.5
No. 2	ca. -0.92	Not applicable	68.2
No. 3	-0.35	-0.85 to 0.14	16.0
No. 4	0.17	-0.24 to 0.58	6.7
No. 5	0.41	0.04 to 0.79	4.1
No. 6	0.62	0.28 to 0.97	1.3
No. 7	0.80	0.47 to 1.12	1.9
No. 8	1.11	0.81 to 1.40	1.5

The retention times of the first two test item peaks in both injections were shorter or about equal to the one for thiourea, which was used as dead time marker. An extrapolation based on the regression data obtained by the injection of reference items was not possible for the first peak and yielded far too low results in the case of the second peak. Therefore, the log Pow of these two peaks was estimated based on the log Pow value of thiourea, which corresponds to -0.92.

Consequently, the log Pow value range obtained for the test item 4,4-dimethyloxazolidine at pH 9.0 and 25 °C, calculated from the mean of two determinations, is <=-0.92 to 1.11.

From a nomenclature point of view, log Pow only applies to the partitioning of the non-charged species between 1-octanol and the aqueous phase. Whether the values determined in this study correspond to log Pow or Dow cannot be clarified in this case, as the test item presents itself as a mixture and its different components have not been elucidated in this study.

The validity criterion was fulfilled for the test item peaks no. 3 to 8. In the case of test item peaks no. 1 and 2, the validity criterion as given in the guideline cannot be applied, as their log Pow values were estimated. However, their respective retention times in both injections were nearly identical suggesting very comparable log Pow values.

Reference 2

Endpoint:

partition coefficient

Type of information:

other: EPA - Reregistration Eligibility Decision

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Guideline:

other: not specified

Type of method:

other: not specified

Remarks:

not specified

Key result

Type:

log Pow

Partition coefficient:

0.73

Remarks on result:

other: Temperatur and pH not specified

Conclusions:

The partition coefficient (logP) of 4,4 - Dimethyloxazolidine  (CAS 51200-87-4) is 0.73 .

Executive summary:

The partition coefficient (logP) of 4,4 - Dimethyloxazolidine  (CAS 51200-87-4) is 0.73 .

Description of key information

For the substance 4,4-dimethyloxazolidine (CAS no. 51200-87-4) there are two reliable studies available for the partition coefficient, one experimental study (ACH 2021) and one literature data source (EPA - Reregistration Eligibility Decision).

In case of the experimental study (ACH 2021), the test item is a mixture, and eight test item related peaks were found in the respective chromatograms used for determination of the log Pow values. Based on the retention times of these peaks, the log Pow value range obtained for the test item 4,4-dimethyloxazolidine at pH 9.0 and 25 °C, calculated from the mean of two determinations, is =-0.92 to 1.11.

The literature log Kow value of the main component (EPA - Reregistration Eligibility Decision) lies within the same range as the experimentally determined values discussed above: 0.73

As the key value for chemical safety assessment, the highest log Kow obtained in the experimental study (ACH 2021) is proposed: 1.11

Key value for chemical safety assessment

Log Kow (Log Pow):

1.11

at the temperature of:

25 °C