cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolane-4-ylmethyl methanesulphonate monohydrochloride

Adsorption / desorption

Link to relevant study record(s)

Reference

Endpoint:

adsorption / desorption: screening

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-08-27 to 2015-08-27

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC))

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method C.19 (Estimation of the Adsorption Coefficient (KOC) on Soil and Sewage Sludge Using High Performance Liquid Chromatography (HPLC))

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: European Commission (EC), Technical Guidance Document on Risk Assessment Part III, Chapter 4.3: “Use of (Quantitative) Structure Activity Relationships ((Q)SARs) - Soil and Sediment Sorption”, 2003.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

See study report

Type of method:

HPLC estimation method

Media:

other: HPLC column

Specific details on test material used for the study:

Test Material SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Janssen Pharmaceutica N.V., I14KB4717
- Expiration date of the lot/batch: 25 November 2016 (retest date)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Analysis of test item in vehicle for concentration, stability, homogeneity was not performed, however preparation was performed with approved procedure and documented in detail. Homogeneity was visually inspected prior to use.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Test preparation material was kept at room temperature no more than 4 hours before animals were dosed. Preparations were stirred on magnetic stirrer during dosing.

Radiolabelling:

no

Details on study design: HPLC method:

EQUIPMENT
- Apparatus: Acquity UPLC system (Waters, Milford, MA, USA)
- Type: Acquity UPLC TUV detector (Waters)
- Column: Acquity UPLC HSS Cyano, 100 mm x 2.1 mm i.d., dp = 1.8 µm (Waters)
- Column temperature: 35°C
- Mobile phase: pH 7 55/45 (v/v) methanol/0.01 M phosphate buffer at pH 7.
- Flow: 0.4 ml/min
- Injection: volume 5 µl
- UV detection: 210 nm (same for test and reference item)

MOBILE PHASES
- Type: 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7
- Solutes for dissolving test and reference substances:
* Solution of the unretained compound:
A 5.0 g/L stock solution of formamide (99.2%, [75-12-7], Alfa Aesar, Karlsruhe, Germany) in methanol was used. The stock solution was diluted to obtain an end solution of 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.
The formamide blank solution was 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.
* Reference substance solutions:
Stock solutions of the reference substances at concentrations of approximately 1 g/L in methanol were used. The stock solutions were diluted to obtain an end solution of 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.
The blank solution for the mixture of reference substances was 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7
* Test solution:
A 1000 mg/L stock solution of the test item was prepared in methanol. The stock solution was diluted to obtain an end solution of 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7. The final concentration of the test item solution was 10.0 mg/L.
The test item blank solution was 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.

- REFERENCE SUBSTANCES:
Acetanilide; Atrazine; Monuron; 2,5-Dichloroaniline; Naphthalene; Benzoic acid phenylester; Fenthion; Phenanthrene; 4,4’-DDT

-DETERMINATION OF RETENTION TIMES
- Quantity of test substance introduced in the column: 10 mg/L.
- Quantity of reference substances: 1 g/L in methanol
- Intervals of calibration: no data

REPETITIONS
- Number of determinations: 2 times (test item solution), 1 time (blank solution)

EVALUATION
- Calculation of capacity factors k': from retention time of reference items, the test item, and then on-sorbed chemical item
- Determination of the log Koc value: a correlation of log k' versus log Koc of the reference items is plotted using linear regression - the log k' value of the test item is then used to calculate its log Koc value

Computational methods:

The capacity factor (k') of each compound was calculated from its retention time. The log k’ values of the references substances were plotted against the known log Koc values. A linear regression program was used to calculate the calibration curve. Linear regression analysis was
performed using the least squares method. The coefficient of correlation (r) was calculated. The log Koc value for the test item was calculated by substituting its mean log k’ in the calibration curve. The value of log Koc obtained from duplicate measurements was within ± 0.25 log units

Key result

Type:

Koc

Value:

1 500 dimensionless

pH:

7

Key result

Type:

log Koc

Value:

3.19 dimensionless

pH:

7

Details on results (HPLC method):

- Retention times (tr,1 and tr,2) of reference substances used for calibration:
* Formamide (t=0):
tr,1: 0.677 min; tr,2: 0.677 min
* Acetanilide:
tr,1: 0.891 min.; tr,2: 0.893 min.
* Atrazazine:
tr,1: 1.101 min.; tr,2: 1.103 min.
* Monuron:
tr,1: 1.243 min.; tr,2: 1.243 min.
* 2,5-Dichloroaniline:
tr,1: 1.467; tr,2: 1.467 min.
* Benzoic acid phenylester:
tr,1: 1.767 min; tr,2: 1.767 min.
* Fenthion:
tr,1: 2.366 min.; tr,2: 2.362 min.
* Phenanthrene:
tr,1: 2.632 min; tr,2: 2.629 min.
* 4,4'-DDT:
tr,1: 7.635 min; tr,2: 7.609 min.

- Details of fitted regression line (log k' vs. log Koc): log k’ = 0.341 x log Koc – 0.873 (r = 0.98, n = 16).
- Average retention data for test substance: 1.787 min

In the chromatogram of the test solution one test item peak with a well-defined retention time of 1.786 minutes was observed. Based on the chromatographic data, the test item was considered stable during the test period.

Validity criteria fulfilled:

yes

Conclusions:

The HPLC method using soil-adsorption-reference data was applied for the determination of the adsorption coefficient (Koc) of JNJ-17336007-AAC (T001202). The test item is a salt. These types of compounds are ionized in solution at each pH value. The UPLC analysis was therefore only performed at neutral pH. Calculations on the pKa values using the Perrin calculation method were not performed. The Koc and log Koc values of the test item at pH 7 were 1500 and 3.19 respectively.

Description of key information

This endpoint is covered with a GLP-study (Ciric, 2016) performed according to standard test guideline OECD 121. The mean log Koc of T001202 was determined to be 3.19 using the HPLC estimation method. The partition coefficients in soil, sediment, suspended matter and raw sewage sludge were calculated from the Koc value and the fraction of organic carbon in the compartment as stipulated in the ECHA guidance Chapter 16 - Table R.16-11.

Key value for chemical safety assessment

Koc at 20 °C:

1 500

Additional information

There is one GLP study available (Ciric, 2016) performed according to standard test guideline OECD 121. The test item is a salt (HCl). These types of compounds are ionized in solution at each pH value. The UPLC analysis was therefore only performed at neutral pH. Calculations on the pKa values using the Perrin calculation method were not performed. The mean log Koc of T001202 was determined to be 3.19 using the HPLC estimation method according to OECD guideline 121. The results of the test can be considered reliable without restriction.

[LogKoc: 3.19]