Benzododecinium chloride

Partition coefficient

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

partition coefficient

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Study period:

2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Reason / purpose for cross-reference:

reference to other study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

Computational approach in OECD Guideline 107

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

Version / remarks:

Computational approach in EU A.8

Deviations:

no

Principles of method if other than guideline:

Firstly, the water solubility of the test substance was determined based on CMC according to ISO 4311 and the n-octanol solubility was determined according to OECD Guideline 107. The partition coefficient was then calculated from ratio of the solubility of the test substance in octanol and water.

GLP compliance:

no

Type of method:

estimation method (solubility ratio)

Partition coefficient type:

octanol-water

Analytical method:

other: Based on solubility ratio

Key result

Type:

Pow

Partition coefficient:

ca. 292 - ca. 433

Temp.:

20 °C

Remarks on result:

other: based on ratio of solubility in n-octanol and water/CMC

Key result

Type:

log Pow

Partition coefficient:

ca. 2.47 - ca. 2.64

Temp.:

20 °C

Remarks on result:

other: based on ratio of solubility in n-octanol and water/CMC

Details on results:

-Solubility of the test substance in n-octanol: 584 - 866 g/L (ref: Hartmann, 2019)
-Solubility of the test substance in water (based on CMC): 2000 mg/L(ref: Hartmann, 2019)

The log Pow was calculated according to the equation:
Pow = solubility of the test substance in n-octanol / solubility of the test substance in water
= 584,000 mg/L / 2000 mg/L to 866,000 mg/L / 2000 mg/L
= 292 to 433

Log Pow: 2.47 to 2.64

Conclusions:

Under the study conditions, the calculated log Kow of the test substance, based on solubility in n-octanol and water (CMC), was determined to be 2.47 to 2.64 at 20°C.

Executive summary:

A study was conducted to determine partition coefficient of the test substance from the ratio of the solubility in n-octanol and water, according to a method similar to OECD Guideline 107 and EU Method A.8. The water solubility of the test substance was determined to be >2000 mg/L (based on critical micelle concentration, CMC) and the n-octanol solubility was determined to be 584 to 866 g/L, according to ISO 4311 and OECD Guideline 107 respectively (Hartmann, 2019). Under the study conditions, the calculated partition coefficient (log Pow or log Kow) of the test substance, based on solubility in n-octanol and water, was determined to be 2.47 to 2.64 at 20°C (Lonza, 2019).

Reference 2

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

From June 27, 2019 to July 09, 2019

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)

Qualifier:

according to guideline

Guideline:

EU Method A.8 (Partition Coefficient - Shake Flask Method)

GLP compliance:

yes (incl. QA statement)

Type of method:

flask method

Remarks:

The partition coefficient (log Pow) can be estimated to be between 0.7 and 1.0. from the priliminary test. For the exact determination of the log Pow in this range the shake flask method was performed.

Partition coefficient type:

octanol-water

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Partition coefficient:

ca. 1.1

Temp.:

24 °C

pH:

ca. 4.1 - ca. 4.7

Remarks on result:

other: mean

Details on results:

The total amount of test substance found in the two phases, the recovery rate and the partition coefficients are shown. As 20 mL of the stock solution were added to each separating funnel, each funnel should contain 22.98 mg of the test substance. The partition coefficient (log Pow) of the test substace was found to be 1.1±0.1 at 24°C (pH 4.1 to 4.7).

Results

Preliminary Test

(a) Water Solubility:

The preliminary test at room temperature showed, that the water solubility of the test substance was in the range of 65 g/L and 175 g/L.

Table 2: Preliminary test for the water solubility

Amount of test substance(mg)	Volume of water (mL)	Time in ultrasonic bath (min)	Remark
104.76	0.1	-	not dissolved
	0.6	2	not dissolved
	1.6	5	dissolved

(b) 1-Octanol solubility:

The preliminary test at room temperature showed, that the 1-octanol solubility of the test substance was in the range of 584 g/L and 866 g/L.

Table 3: Preliminary test for the 1-octanol solubility

Total amount of test substance (g)	Volume of 1-octanol (mL)	Stirring time at RT (min)	Remark
0.62	5	45	dissolved
1.51		45	dissolved
2.28		50	dissolved
2.92		75	dissolved
4.33		915	not dissolved

The partition coefficient (log Pow) can be estimated to be between 0.7 and 1.0. For the exact determination of the log Pow in this range the shake flask method is recommended.

Main Test:

The phases of the shake-flask-method were measured twice by means of HPLC. The results of these measurements are summarized in Table 4 and Table 5.

Table 4 : Concentrations in the aqueous phases

Separating funnel	pH values	Measured concentration (mg/mL)	Mean concentration (mg/mL)
1a	4.71	196.6 / 197.4	197.0
1b	4.54	220.1 / 208.9	214.5
2a	4.47	162.1 / 163.3	162.7
2b	4.52	156.8 / 164.6	160.7
3a	4.06	188.9 / 187.0	187.9
3b	4.13	150.5 / 155.9	153.2

Table 5 : Concentrations in the 1-octanol phases

Separating funnel	Measured concentration (mg/mL)	Mean concentration (mg/mL)
1a	3847.3 / 3891.8	3869.5
1b	3730.8 / 3757.1	3743.9
2a	2000.1 / 2003.7	2001.9
2b	1968.8 / 1824.0	1896.4
3a	2004.3 / 1986.6	1995.4
3b	1955.8 / 1986.5	1971.1

Table 6: Results of shake-flask method

Separating funnel	Total amount of test substance in separating funnel (mg)	Recovery rate (%)	Pow	log Pow
1a	85.27	116.7	19.641	1.3
1b	83.46	114.3	17.451	1.2
2a	86.59	118.5	12.302	1.1
2b	82.29	112.6	11.801	1.1
3a	83.58	114.4	10.619	1
3b	81.91	112.1	12.868	1.1
Mean value				1.1
Standard deviation				0.1

To verify the accuracy of the analytical method two fresh prepared standard solutions (prepared with the test substance) were measured in between the samples of the shake-flask­ method. The recovery rate of the measured standard solutions was in the range from 90.3 % - 105.6 % which shows a sufficient accuracy of the analytical method.

Conclusions:

Under the study conditions, partition coefficient (log Pow) of the test substance was determined to be 1.1 ± 0.1 at 24°C

Executive summary:

A study was conducted to determine the partition coefficient of the substance, using shake flask method, according to the OECD Guideline 107 and EU Method A.8, in compliance with GLP. Under the study conditions, partition coefficient (log Pow) of the test substance was determined to be 1.1 ± 0.1 at 24°C (Hartmann, 2019)

Description of key information

The partition coefficient of the substance was determined using shake flask and solubilty ratio methods according to the OECD Guideline 107 and EU Method A.8 (Hartmann, 2019).

Key value for chemical safety assessment

Log Kow (Log Pow):

2.63

Additional information

- Log Kow based on solubility ratios in n-octanol and water solubilty (represented by CMC): 2.47 to 2.63 at 20-24°C

- Log Kow based on shake flask method: 1.1 ± 0.1 at 24°C

As the test substance is a surfactant, the log Kow value based on solubility ratio, which is considered as the most pragmatic approach for surfactants as per the ECHA guidance, has been considered further for hazard/risk assessment.