5-chloro-1,3-dihydro-1-(4-piperidinyl)-2H-benzimidazol-2-one

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:

2015-09-02 to 2015-09-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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

GLP compliance:

yes (incl. QA statement)

Type of method:

HPLC estimation method

Media:

other: HPLC column

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Analytical purity: >98.5% (based on chromatographic purity HPLC: 99.96%, base titration: 98.5%, acid titration: 100.4%)
- Source and lot/batch No.of test material: A14JB3414
- Expiration date of the lot/batch: 01 October 2015 (retest date)
- Purity test date: 2014-12-22 (certificate of analysis release date)


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stable under storage conditions until 01 October 2015 (retest date)

Radiolabelling:

no

Test temperature:

Column temperature 35°C.

Details on study design: HPLC method:

EQUIPMENT
- Apparatus: Acquity UPLC system (Waters, Milford, MA, USA)
- Type: Acquity UPLC TUV detector (Waters)
- Type, material and dimension of analytical (guard) column: Acquity UPLC HSS Cyano, 100 mm x 2.1 mm i.d., dp = 1.8 µm (Waters)
- Detection: 210 nm (UV)
- Column temperature: 35°C

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 2000 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
- Identity: combined reference solution containing Acetanilide, Monuron, 2,5-Dichloroaniline, Napthalene, Benzoic acid phenylester, Fenthion, Phenanthrene and 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

Key result

Type:

log Koc

Value:

5.35 dimensionless

pH:

7

Remarks on result:

other: mean of 2 analyses

Key result

Type:

Koc

Value:

220 000 dimensionless

pH:

7

Remarks on result:

other: mean of 2 analyses

Details on results (HPLC method):

- Retention times (tr,1 and tr,2) of reference substances used for calibration:
* Formamide (t=0):
tr,1: 0.659 min; tr,2: 0.659 min
* Acetanilide:
tr,1: 0.861 min.; tr,2: 0.860 min.
* Monuron:
tr,1: 1.054 min.; tr,2: 1.053 min.
* 2,5-Dichloroaniline:
tr,1: 1.185; tr,2: 1.183 min.
* Naphthalene:
tr,1: 1.386 min.; tr,2: 1.384 min.
* Benzoic acid phenylester:
tr,1: 1.648 min; tr,2: 1.646 min.
* Fenthion:
tr,1: 2.160 min.; tr,2: 2.155 min.
* Phenanthrene:
tr,1: 2.377 min; tr,2: 2.375 min.
* 4,4'-DDT:
tr,1: 5.610 min; tr,2: 5.596 min.

- Details of fitted regression line (log k' vs. log Koc): log k’ = 0.315 x log Koc – 0.834 (r = 0.98, n = 16)
- Average retention data for test substance: 5.344 min
- Koc test substance = 2.2 x 10^5

Transformation products:

not measured

Calculation of pK_avalues

The following pK_avalues for acidic and basic groups in the molecular structure of the test item were calculated using the Perrin calculation method:

Acidic:

(AR)NHCOR: pKa 16.22

Basic:

RRNH2 +: pKa 9.94

RARN(R1R2): pKa -1.58

(AR)NHCOR: pKa -2.20

Based on these values, it was concluded that the test item is ionised for at least 10% within pH 5.5 to 7.5. Testing therefore should be performed with both the ionised and non-ionised form.

Testing with the non-ionised form at pH between 10.9 and 15.2 is technically not possible. The cyanopropyl columns prescribed by the guidelines are not stable outside the pH range 2 to 8.

Testing with the ionised form was performed at pH 7.

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-119743-AAA (T000990). Based on pKa calculations, it was concluded that the test item is ionised for at least 10% within pH 5.5 to 7.5. Testing therefore should be performed with both the ionised and non-ionised form according to the guidelines.
Testing with the non-ionised form at pH between 10.9 and 15.2 is technically not possible. The cyanopropyl columns prescribed by the guidelines are not stable outside the pH range 2 to 8. Testing with the ionised form was performed at pH 7. The mean log Koc of T000990 was determined to be 5.35 using the HPLC estimation method according to OECD guideline 121. The results of the test can be considered reliable without restriction.

Description of key information

This endpoint is covered with a GLP-study (Brekelmans, 2016) performed according to standard test guideline OECD 121. The mean log Koc of T000990 was determined to be 5.35 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:

220 000

Additional information

There is one GLP study available (Brekelmans, 2016) performed according to standard test guideline OECD 121. Based on pKa calculations, it was concluded that the test item is ionised for at least 10% within pH 5.5 to 7.5. Testing therefore should be performed with both the ionised and non-ionised form according to the guidelines. However testing with the non-ionised form at pH between 10.9 and 15.2 was technically not possible. The cyanopropyl columns prescribed by the guidelines are not stable outside the pH range 2 to 8. Therefore only testing with the ionised form was performed. Amines have been demonstrated to interact with the HPLC column stationary phase by mechanisms other than partitioning. Therefore the estimation of the adsorption coefficient of ionised substances from the capacity factor of reference substances of known log10 Koc values is not considered valid. This was concluded not to impact the validity of the study, as irrespective of an anticipated increased water solubility and reduced partition coefficient value, the mobility of substances in soil is typically reduced on formation of a cationic state due to strong secondary ionic interactions with clay particles and other ion exchange sites within the soil. The mean log Koc of T000990 was determined to be 5.35 using the HPLC estimation method according to OECD guideline 121. The results of the test can be considered reliable without restriction.

[LogKoc: 5.35]