N6-Benzoyl-5′-O-(4,4′-dimethoxytrityl)-2′-deoxyadenosine-3′-O-[O-(2-cyanoethyl)-N,N′-diisopropylphosphoramidite]

Biodegradation in water: screening tests

Link to relevant study record(s)

Reference

Endpoint:

biodegradation in water: ready biodegradability

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Key result

Parameter:

% degradation (O2 consumption)

Value:

5

Sampling time:

28 d

Remarks on result:

other: based on ThOD(NH4)

Key result

Parameter:

% degradation (O2 consumption)

Value:

4

Sampling time:

28 d

Remarks on result:

other: based on ThOD(NO3)

Details on results:

The test item 5′-O-[bis(4-methoxyphenyl) phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite contains nitrogen; therefore the evaluation of biodegradation has to be based on ThODNH4 and ThODNO3. The criterion for ready biodegradability under the conditions of a manometric respirometry test is the degradation of the test item of at least 60%, reached within a 10-day window; the 10-day window starts
when the degradation of the test item reaches 10% degradation.
5′-O-[bis(4-methoxyphenyl) phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite never reached 10% biodegradation. The mean biodegradation at test end after 28 days was 5% (based on ThODNH4, see Figure 1) and 4% (based on ThODNO3, see Figure 2).

Results with reference substance:

The reference item sodium benzoate was sufficiently degraded to 73% after 14 days and to 84 % after 28 days of incubation (based on ThODNH4). The percentage biodegradation of the reference item confirms the suitability of the used aerobic activated sludge inoculum.

Validity Criteria of the Study

-       Inoculum Control: The oxygen demand of the inoculum control (medium and inoculum) was 20 mg O2/L and thus not greater than 60 mg O2/L within 28 days as required by the test guideline. 

-       pH-Value: The pH-value of the test item flasks at the end of the test was 7.4 and therefore within the range of pH 6.0 to 8.5 as required by the test guideline.

-       Reference Item: The percentage degradation of the reference item should reach the level for ready biodegradability (> 60 %) within 14 days as required by the test guideline. The reference item sodium benzoate was degraded to more than 60 % after 7 days of incubation.

-       Test Item: The difference of duplicate values for the degradation of the test item at the plateau, at the end of the test was less than 20 %. The difference of duplicate values at day 28 differed by 10 % (based on ThODNH4) and 8 % (based on ThODNO3). The validity criterion was fulfilled.

-       Toxicity Control: If in a toxicity test, containing both the test substance and a reference compound less than 25 % biodegradation occurred within 14 days (ThODNH4), the test substance can be assumed to be inhibitory. The biodegradation was 32% (based on ThODNH4) and 29 % (based on ThODNO3) at day 14; the test item was not inhibitory. 

Validity criteria fulfilled:

yes

Interpretation of results:

not readily biodegradable

Conclusions:

The mean biodegradation of the test item 5′-O-[bis(4-methoxyphenyl) phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite at test end after 28 days was 5 % (based on ThODNH4) and 4 % (based on ThODNO3).

Executive summary:

The biodegradation of 5′-O-[bis(4-methoxyphenyl) phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite was studied in reconstituted water (pH 7.4 – 7.6) inoculated with activated sludge from a domestic sewage treatment plant (stock suspension of 3.5 g/L on dry matter base and a final sludge concentration in test flasks of 28.7 mg sludge/L). The test item was applied with 103.5 mg a.i./L.  The experiment was conducted in accordance with the OECD test guideline 301 F “Ready Biodegradability: Manometric Respirometry Test”, and in compliance with the OECD-GLP standards. The test system consisted of test flasks containing a volume of approximately 500 mL. The pressure decrease in the reaction vessels was measured over complete experimental phase of 28 days using the BSB/BODSensor- System, Aqualytic Dortmund, Germany. The test flasks were closed gas-tight by a measuring head. Potassium hydroxide solution (45 %) was used for trapping the produced carbon dioxide. The amount of O2 consumed by the activated sludge was calculated from the decrease of pressure in the reaction vessel.

The test item contains nitrogen; therefore the evaluation of biodegradation has to be based on ThODNH4 and ThODNO3. The criterion for ready biodegradability under the conditions of a manometric respirometry test is the degradation of the test item of at least 60 %, reached within a 10-day window; the 10-day window starts when the degradation of the test item reaches at least 10 % degradation. The test item never reached 10 % biodegradation. The mean biodegradation of the test item at test end after 28 days was 5 % (ThODNH4) and 4 % (ThODNO3). Therefore, 5′-O-[bis(4-methoxyphenyl) phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite is considered to be not readily biodegradable.

This information is used in a read-across approach in the assessment of the target substance.

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Description of key information

One study is available for biodegradation in water which can be used for read-across to N-benzoyl-5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-deoxyadenosine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite]:

The Study by Hammesfahr (2018) was conducted according to GLP principles and followed the OECD test guideline 301 F. The mean degradation rate of 5′-O-[bis(4-methoxyphenyl) phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite in a test according to the OECD method 301 F after 28 days was 5 % (based on ThODNH4) and 4 % (based on ThODNO3). Therefore, the test item is not readily biodegradable.

 

This information is used in a read-across approach in the assessment of the target substance.

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Key value for chemical safety assessment

Biodegradation in water:

under test conditions no biodegradation observed

Type of water:

freshwater