Antimony, mixed dipentyldithiocarbamate and bis(2-ethylhexyl)dithiocarbamate complexes

Partition coefficient

Link to relevant study record(s)

Reference

Endpoint:

partition coefficient

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 February 2018 - 25 October 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

Due to the complex nature of the Test Item, it was not possible to determine a result.

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC method

Partition coefficient type:

octanol-water

Specific details on test material used for the study:

Physical state: Clear amber liquid
Stability under storage conditions: Stable at room temperature
Storage condition of test material: Ambient

Analytical method:

high-performance liquid chromatography

Key result

Type:

log Pow

Remarks on result:

not determinable

Remarks:

The partition coefficient (LogPow) for the Test Item was “not technically feasible”.

Details on results:

The partition coefficient (LogPow) for the Test Item was “not technically feasible”.

It was not possible to obtain a test solution suitable for analysis by HPLC. In most cases the Test Item was not fully soluble at 0.01 % v/v and, where the Test Item was fully dissolved, the resulting solution was too viscous to allow HPLC analysis. Additionally, the HPLC method is not considered suitable for metal complexes (OECD Guideline 117).

During the feasibility testing, test solutions were also prepared using 100 % n-octanol at 5 and 10 m/m % . The Test Item, by visual inspection, appeared to be fully soluble at 10 m/m % indicating that the solubility of the Test Item in n-octanol is estimated to exceed 10 m/m %. Specifically, 0.51832 g and 1.01984 g aliquots of the Test Item were weighed into glass vials and 9.50086 g and 9.00109 g of n-octanol were added to each vial, respectively. The test solutions were vortex mixed and allowed to stand for 5 minutes. A visual assessment of the solutions confirmed clear, amber solutions were obtained, suggesting that the Test item was fully soluble at these concentrations.

Based upon the solubility in n-octanol, the shake flask method for determination of the n-octanol solubility was not considered appropriate as there is a risk of interference from gel formation at higher concentrations which can impact upon quantitation.

EU guideline A8(EC), which is based upon OECD guideline 107 for partition coefficient determination, does state that where the shake flask method is not applicable then an estimation of the LogP_owmay be provided based upon individual water and n-octanol solubilities. Therefore, an estimate using the limit values was performed for information purposes only.

The water solubility for the Test Item was determined independently of this study[1]and reported as < 4.54 x10^-5g/L at 20°C (< 0.0454 mg/L).

The non-specific solubility of the Test item in n-octanol was assessed by visual assessment in this report and estimated to be > 10 m/m % atambient laboratory temperature.Assuming a density of water of 1 g/mL, the solubility of the Test Item in n-octanol is estimated to be greater than 100 g/L (> 100,000 mg/L).

The estimated LogP_owvalue was calculated as:

Log10 Solubility in n-Octanol/Solubility in water

Therefore:

LogPow = Log10 >100 g/L / <0.0000454 g/L = >6.34

Given that both the water solubility and n-octanol solubility are limit values, the LogP_ow for the Test Item is estimated to exceed 6.34. This estimate was not obtained in accordance with testing guidelines for estimating partition coefficient based on individual solubilities and is included here for information purposes only.

Conclusions:

The partition coefficient (LogPow) for the Test Item was “not technically feasible”.

Given that both the water solubility and n-octanol solubility are limit values, the LogPow for the Test Item is estimated to exceed 6.34. This estimate was not obtained in accordance with testing guidelines for estimating partition coefficient based on individual solubilities and is included here for information purposes only.

Executive summary:

The partition coefficient (LogP_ow) for the Test Itemwas “not technically feasible”.

Given that both the water solubility and n-octanol solubility are limit values, the LogP_ow for the Test Item is estimated to exceed 6.34. This estimate was not obtained in accordance with testing guidelines for estimating partition coefficient based on individual solubilities and is included here for information purposes only.

Description of key information

The partition coefficient (LogPow) for the Test Item was “not technically feasible”. Given that both the water solubility and n-octanol solubility are limit values, the LogPow  for the Test Item is estimated to exceed 6.34. This estimate was not obtained in accordance with testing guidelines for estimating partition coefficient based on individual solubilities and is included here for information purposes only (Intertek Pharmaceutical Services, 2018).