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Partition coefficient

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Endpoint:
partition coefficient
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September 14, 2016 - September 23, 2016
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
EPA OPPTS 830.7550 (Partition Coefficient, n-octanol / H2O, Shake Flask Method)
Deviations:
no
GLP compliance:
yes
Type of method:
flask method
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
-Name of substance as used in the study: MTDID 15670
- Source and lot/batch No.of test material: 605803
- Purity: 98.4%:
- Expiration date of the lot/batch:October 23, 2016
Analytical method:
liquid chromatography
mass spectrometry
Key result
Type:
log Pow
Partition coefficient:
<= 0.75
Temp.:
22 °C
pH:
6
Details on results:
The Kow values ranged from 4.83 to 6.48 for all six samples. The average Kow values were 5.67, 4.87 and 6.45 for the 1:1, 1:2 and 2:1 octanol: water ratio. The overall average Kow was 5.66, and overall RSD% was 14%.

The log Kow values ranged from 0.684 to 0.812 for all six samples. The average log Kow values were 0.754, 0.687 and 0.810 for the 1:1, 1:2 and 2:1 octanol: water ratio. The overall average log Kow was 0.750, RSD% of log values were not calculated.

The cation CCVs recoveries were < 75% for CCV samples with cation concentrations of ≤ 77.5 ng/mL (≤ 100 ng/mL MTDID 15670). The CCV recoveries for cation concentration range of 194 - 775 ng/mL (250 -1000 ng/mL MTDID 15670) have recoveries of 83.2 - 94.3%. Since the measured on-column cation concentration were within the range of 194 ng/mL and 775 ng/mL, the low recoveries for CCV samples with ≤ 77.5 ng/mL MTDID15670 cation concentration would not affect the measured MTDID 15670 cation concentrations in the samples.

The average mass balance for measured MTDID 15670 in water and octanol versus the known amount added was 100% (RSD=5.7%) for all three different ratios of octanol/ water tested (data not shown).

MTDID15670 cation is subject to rapid hydrolysis at pH 7 and 23 °C. The measured cation concentrations in water may be underestimated values, which may result in overestimated Kow values. Therefore, the log Kow is reported as ≤ 0.750.

Table 1: Summary of n-Octanol/Water Partition Coefficient for MTDID 15670

 

Ratio

(n-Octanol: Aqueous)

Replicate

MTDID 15670 in octanol phase

(µg/mL) (a)

MTDID 15670 in water phase

(µg/mL) (a)

 

 

Kow

 

Log Kow

 

 

Average

Kow (RPD%)

 

Average

Log Kow (RPD%)

1:1

1

428

73.9

5.79

0.763

 

 

1:1

2

409

73.7

5.56

0.745

5.67

0.754 (2.4%)

1:2

1

334

69.1

4.83

0.684

 

 

1:2

 

2

343

69.9

4.90

0.691

4.87

0.687 (0.92%)

2:1

1

501

78.1

6.42

0.808

 

 

2:1

2

495

76.4

6.48

0.812

6.45

0.810 (0.48%)

Overall Average

 

  

 

5.66

0.750

5.66

0.750

Overall RSD%

 

 

14%

N/A

14%

N/A

 

(a)    Concentrations are sum of cation and anion, which were measured separately.

Results are the average of duplicate aliquots.

Conclusions:
Log Kow of MTDID 15670 was measured to be ≤ 0.750 under the condition of this study.
Executive summary:

The n-Octanol/Water Partition Coefficient (log Kow) of MTDID was determined according to U.S EPA guidance document OPPTS 830.7550 "Partition Coefficient (n-Octanol/Water), Shake Flask Method".

Duplicate samples of MTDID 15670 were prepared in each of the three octanol/water ratios (1:1, 1:2, and 2:1). The six samples were rotated 180 ° about their transverse axis for 3600 rotations over a period of 2 hours to ensure proper mixing of the test system solvents. The samples were then centrifuged at 1500 RPM for 10 minutes to facilitate phase separation. Duplicate aliquots of n-octanol phase were carefully removed. The octanol phase samples were diluted with methanol, then further diluted with aqueous 0.1% acetic acid containing PhI-Urea (IS) for cation analysis, or with water containing PFBS (IS) for anion analysis. After the octanol phase sample removal, duplicate water phase samples were carefully removed and the pH of each aqueous samples were measured. The water phase samples were diluted with aqueous 0.1% acetic acid with PhI-Urea (IS) intended for cation analysis, or with water with PFBS (IS) for anion analysis.

MTDID 15670 contains asulfonium cation and a tetrafluoroborate anion components. The cation and anion concentration were measured independently in each of the samples, and MTDID 15670 concentration was determined by summing the measured cation and anion concentration in each of the octanol phase and water phase.

The determined Kow for MTDID 15670 was 5.66 (RSD 14%) and calculated to a log Kow of 0.750. The average mass balance for measured MTDID 15670 in water and octanol versus the known amount added was 100% (RSD=5.7%) for all three different ratios of octanol/ water tested.

This is a guideline study conducted under GLP compliance. However, MTDID15670 cation is subject to rapid hydrolysis at pH 7 and 23 °C. The measured cation concentrations in water may be underestimated values, which may result in overestimated Kow values. Therefore, the log Kow is reported as ≤ 0.750. This is considered reliable with restrictions, and adequate for risk assessment and PBT purposes.

Endpoint:
partition coefficient
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
2016-07-11 to 2016-10-21
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
Remarks:
Test substance rapidly hydrolyze at neutral pH. Concentration in water was measured at pH 2 and is not relevant to the environmental condition.
Qualifier:
no guideline followed
Principles of method if other than guideline:
log Kow was calculated based on the ratio of individually measured octanol and water solubility
GLP compliance:
no
Type of method:
estimation method (solubility ratio)
Partition coefficient type:
octanol-water
Type:
log Pow
Partition coefficient:
0.78
Details on results:
Two experiments were conducted to measure the solubility of MTDID 15670 in octanol and in water, respectively. Since MTDID 15670 contains a sulfonium cation and a tetrafluoroborate anion components, the cation and anion concentrations in each of octanol and water were measured independently, and MTDID 15670 solubility in octanol and in water were determined by summing the measured cation and anion concentration in each of the octanol and water solvent.

The overall average solubility of MTDID 15670 in octanol was 6120 mg/L as measured in a preliminary study (E16-0636). The overall average solubility of MTDID 15670 in water was 1010 mg/L as measured in a GLP and guideline study (GLP16-0008).

Based on these individually measured solubilities, the Kow was calculated as the ratio of MTDID 15670 concentration in octanol/MTDID15670 concentration in water. The calculated Kow for MTDID 15670 was 6.06, the calculated log Kow was 0.78. However, the MTDID15670 waster solubility was measured at pH 2, and is disregarded study due to unsuitable test system.



Conclusions:
The calculated log Kow was disregarded due to unsuitable test system for the water solubility study.
Executive summary:

The partition coefficient of a test substance may be estimated based on the ratio of individual measured n-octanol and water solubility.

Two separate studies were conducted to measure the solubility of MTDID 15670 in n-octanol and in water, respectively. The overall average solubility of MTDID 15670 in octanol was 6120 mg/L as measured in a preliminary study (E16-0636).  The overall average solubility of MTDID 15670 in water was 1010 mg/L as measured in a GLP and guideline study (GLP16-0008). Based on these individually measured solubility, the calculated Kow for MTDID 15670 was 6.06, the calculated log Kow was 0.78.

The measured octanol solubility is considered reliable with restriction. However, the MTDID15670 water solubility was measured at pH 2, and is a disregarded study due to unsuitable test system. Consequently, the calculated log Kow is also a disregarded study.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2018-05-21 to 2018-05-22
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QMRF and QPRF attached
Qualifier:
according to guideline
Guideline:
other: Guidance on information requirements and chemical safety assessment: Chapter R.6: QSARs and grouping of chemicals
Deviations:
no
GLP compliance:
no
Remarks:
QSAR model
Type of method:
other: calculation method (fragments) KOWWIN v1.68 as implemented through EPI Suite v4.11
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
For hydrolysis product of MTDID 15670:
Dodecyl ethyl sulfide
CAS# N/A
SMILES : S(CCCCCCCCCCCC)CC
Key result
Type:
log Pow
Partition coefficient:
6.81
Conclusions:
Dodecyl ethyl sulfide is a hydrolysis product of MTDID 15670. Dodecyl ethyl sulfide has an estimated log Kow of 6.81 using KOWWIN v1.68 as implemented through EPISuite v4.11.
Executive summary:

Dodecyl ethyl sulfide is identified as one of the hydrolysis products of MTDID 15670. The logarithm of the partition coefficient n-octanol/water (log Kow) of dodecyl ethyl sulfide was estimated to be 6.81 using the KOWWIN v1.68 QSAR as implemented through EPI Suite v4.11. The software is an accepted, valid model for estimation of partition coefficient. The structure of dodecyl ethyl sulfide is within the parametric domain of the model (molecular weight, maximum number of structural fragments per structure, predicted log Kow). The use of this QSAR to predict log Kow for this substance was determined to be applicable and reliable based on representation of analogous substances within the training set and performance statistics (a correlation coefficient (r^2) of 0.976, a standard deviation of 0.312 and an absolute mean error of 0.192) derived from a comparison of experimental and estimated log Kow values for 10 representative analogous substances.

This study is classified as an acceptable QSAR and satisfies the requirements for partition coefficient study. It is pertinent to the fate of MTDID 15670 and may be used for risk analysis, classification and labelling, and PBT analysis.

Endpoint:
partition coefficient
Type of information:
(Q)SAR
Adequacy of study:
supporting study
Study period:
2018-05-17 to 2018-05-18
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
QMRF and QPRF attached
Qualifier:
according to guideline
Guideline:
other: Guidance on information requirements and chemical safety assessment: Chapter R.6: QSARs and grouping of chemicals
Deviations:
no
GLP compliance:
no
Remarks:
QSAR model
Type of method:
calculation method (fragments)
Remarks:
KOWWIN v1.68 as implemented through EPI Suite v4.11
Partition coefficient type:
octanol-water
Specific details on test material used for the study:
For hydrolysis product of MTDID 15670:
Crotononitrile
CAS# 4786-20-3
SMILES: C(=CC)C(#N)
Key result
Type:
log Pow
Partition coefficient:
0.62
Conclusions:
Crotononitrile has an estimated log Kow of 0.62 using KOWWIN v1.68 as implemented through EPI Suite v4.11.
Executive summary:

Crotononitrile is identified as one of the hydrolysis products of MTDID 15670. The logarithm of the partition coefficient n-octanol/water (log Kow) of crotononitrile was estimated to be 0.62 using the KOWWIN v1.68 QSAR as implemented through EPI Suite v4.11. The software is an accepted, valid model for estimation of partition coefficient. The structure of crotononitrile is within the parametric domain of the model (molecular weight, maximum number of structural fragments per structure, predicted log Kow). The use of this QSAR to predict log Kow for this substance was determined to be applicable and reliable based on representation of analogous substances within the training set and performance statistics (0.9734 correlation coefficient (r-squared), a standard deviation of 0.095 and an absolute mean error of 0.193) derived from a comparison of experimental and estimated log Kow values for 13 representative analogous substances.

This study is classified as an acceptable QSAR and satisfies the requirements for partition coefficient study. It is pertinent to the fate of MTDID 15670 and may be used for risk analysis, classification and labelling, and PBT analysis.

Description of key information

Log Kow of MTDID 15670 was reported to be ≤ 0.750.

Key value for chemical safety assessment

Additional information

The n-Octanol/Water Partition Coefficient (log Kow) of MTDID 15670 was measured according to U.S EPA guidance document OPPTS 830.7550 "Partition Coefficient (n-Octanol/Water), Shake Flask Method". Duplicate samples of MTDID 15670 were prepared in each of the three octanol/water ratios (1:1, 1:2, and 2:1) and analyzed using LC/MS/MS. MTDID 15670 contains a sulfonium cation and a tetrafluoroborate anion components. The cation and anion concentration were measured independently in each of the samples, and MTDID 15670 concentration was the sum of the measured cation and anion concentration in each of the octanol phase and water phase. This is a guideline study conducted under GLP compliance. However, MTDID15670 cation is subject to rapid hydrolysis at pH 7 and 23 °C. The measured cation concentrations in water may be underestimated values, which may result in overestimated Kow values. Therefore, the log Kow is reported as ≤ 0.750. This is considered reliable with restrictions (Klimisch 2) and a key study, and is adequate for risk assessment and PBT purposes.

The partition coefficient of MTDID 15670 was also estimated based on the ratio of individually measured n-octanol and water solubility. However, the MTDID15670 water solubility was measured at pH 2, and is a disregarded study due to unsuitable test system. Consequently, the calculated log Kow is also a disregarded study (Klimisch 3).

MTDID 15670 dissociates in water and is subject to hydrolysis. The identified products are crotononitrile, dodecyl ethyl sulfide, and BF4(-) anion. The BF4(-) anion is an inorganic compound and the partition coefficient property does not apply.

The log Kow values of crotononitrile and dodecyl ethyl sulfide were estimated using the KOWWIN v1.68 QSAR as implemented through EPI Suite v4.11. The software is an accepted, valid model for estimation of partition coefficient. The use of this QSAR to predict log Kow for these compounds was determined to be applicable and reliable based on representation of analogous substances within the training set and performance statistics derived from a comparison of experimental and estimated log Kow values for representative analogous substances. Crotononitrile has an estimated log Kow of 0.62. Dodecyl ethyl sulfide has an estimated log Kow of 6.81. These studies are classified as acceptable QSARs and satisfy the requirements for partition coefficient study and are supporting studies. They are pertinent to the fate of MTDID 15670 and may be used for risk analysis, classification and labelling, and PBT analysis.