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

Endpoint summary

Description of key information

No data is available for the target substance N-benzoyl-5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-deoxyadenosine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite]. Thus, data from a suitable read-across partner was used to assess the acute oral toxicity of the target substance. In an acute oral toxicity study in rats conducted according to OECD 423, 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] (source substance) was applied to rats. One animal out of six died at the limit dose of 2000 mg/kg bw. Based on the results, the LD50 can be considered to be greater 2000 mg/kg bw and the LD50 cut-off value was determined to be 2500 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

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

Reason / purpose for cross-reference:

read-across source

Preliminary study:

n.a

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: One animal died spontaneously one day post-dosing. All remaining animals survived

Mortality:

One animal treated with the test item at a dose of 2000 mg/kg bw died spontaneously one day post-dosing. All remaining animals survived until the end of the study.

Clinical signs:

other: The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, hunched posture, piloerection and half eyelid closure. All symptoms recovered by day 1 after dosing.

Gross pathology:

At necropsy, no treatment-related macroscopic findings were observed in any animal in either step.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study in rats conducted according to OECD 423, one animal out of six died at the limit dose of 2000 mg/kg bw. Based on the results, the LD50 can be considered to be greater 2000 mg/kg bw and the LD50 cut-off value was determined to be 2500 mg/kg bw.

Executive summary:

In an acute oral toxicity study (acute toxic class method, OECD 423), two groups of fasted, 8 -10 weeks old, female Wistar rats (3 rats/group) were given a single oral dose of the test item (99.7 % purity) in corn oil at the limit dose of 2000 mg/kg bw and were observed for 14 days. One animal died spontaneously one-day post-dosing. All remaining animals survived until the end of the study. The most relevant clinical findings in the animals treated with the test item at a dose of 2000 mg/kg bw were reduced spontaneous activity, hunched posture, piloerection and half eyelid closure. All symptoms recovered within 2 days. Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain. At necropsy, no treatment-related macroscopic findings were observed in any animal of any step. Based on the results from this study, the oral LD50 in rats is considered to exceed 2000 mg/kg bw and the and the LD50 cut–off value was determined to be 2500 mg/kg bw.

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

For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

GLP guideline study

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No data is available for the target substance N-benzoyl-5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-deoxyadenosine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite]. Thus, data from a suitable read-across partner was used to assess the acute oral toxicity of the target substance. Details on the read-across rationale are provided in IUCLID section 13.

In an acute oral toxicity study in rats conducted according to OECD 423, 5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-deoxythymidine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] (source substance) was applied to rats. One animal out of six died at the limit dose of 2000 mg/kg bw. Based on the results, the LD50 can be considered to be greater 2000 mg/kg bw and the LD50 cut-off value was determined to be 2500 mg/kg bw.

Justification for classification or non-classification

Based on the available data from a suitable read-across partner, the target substance N-benzoyl-5′-O-[bis(4-methoxyphenyl)phenylmethyl]-2′-deoxyadenosine, 3′-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] does not warrant classification for acute toxicity. The LD50 value for the oral route was above the limit value for classification (2000 mg/kg bw).