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

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

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 genotoxic potential of the target substance.

The mutagenic potential of 5’-O-[bis(4-methoxyphenyl)phenylmethyl]-2’-deoxythymidine, 3’-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] (source substance) was investigated in a bacterial reverse gene mutation assay conducted according to OECD 471 with and without metabolic activation. There was no increase of mutant colonies compared to the negative control observed in all strains. Consequently, the test item is considered to be non-mutagenic.

Link to relevant study records

Reference

Endpoint:

in vitro gene mutation study in bacteria

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

Key result

Species / strain:

S. typhimurium, other: TA98, TA100, TA102, TA1535 and TA1537

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

In two independent experiments several concentrations of the test item were used. Each assay was conducted with and without metabolic activation. The concentrations, including the controls, were tested in triplicate. Precipitation of the test item was observed in all tester strains used in experiments I and II at the higher concentrations of 2500 µg and 5000 µg/plate (with and without metabolic activation).
No toxic effects of the test item were noted in any of the five tester strains up to the highest concentration evaluated with and without metabolic activation inexperiments I and II. No biologically relevant increases in revertant colony numbers of any of the five tester strains were observed following treatment with the test item at any concentration level, neither in the presence nor absence of metabolic activation in experiment I and II. All criteria of validity were met.

Remarks on result:

other: Experiment II, precipitation was observed in all tester strains at 2500 and 5000 µg/plate

Table 2: Results of the pre-experiment

Substance	Dose (µg/plate)	TA98				TA100
		Mutation Factor				Mutation Factor
		without S9		with S9		without S9		with S9
Solvent Control (DMSO)		1.0		1.0		1.0		1.0
4-NOPD	10.0	23.2		-		-		-
NaN3	10.0	-		-		8.3		-
2-AA	2.50	-		58.3		-		22.0
Test Item	3.16	0.7		0.9		1.2		1.1
	10.0	0.9		0.8		1.1		1.1
	31.6	1.2		0.8		1.0		1.1
	100	1.1		0.9		1.1		1.1
	316	0.8		1.1		1.0		1.0
	1000	1.3		0.9		0.9		1.2
	2500	0.8		0.8		1.2		1.2
	5000	0.6		0.9		1.1		1.1

*Mutation factor= mean revertants (test item)/ mean revertants (vehicle control)

Conclusions:

Under the experimental conditions reported, 5’-O-[bis(4-methoxyphenyl)phenylmethyl]-2’-deoxythymidine, 3’-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] did not cause gene mutations in an Ames Test conducted according to OECD 471. Therefore, the test item is considered to be non-mutagenic in this bacterial reverse gene mutation assay.

Executive summary:

In a bacterial reverse gene mutation assay conducted according to OECD guideline 471, strains TA98, TA100, TA102, TA1535 and TA1537 of Salmonella typhimurium were exposed to 5’-O-[bis(4-methoxyphenyl)phenylmethyl]-2’-deoxythymidine, 3’-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] (99.7% purity) in DMSO at concentrations of 31.6, 100, 316, 1000, 2500 and 5000 µg/plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background in all tester strains in both experiments (plate incorporation and pre-incubation). Based on the results, the test item is considered to be non-mutagenic in the bacterial reverse gene mutation assay.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OPPTS 870.51001; OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.

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 (negative)

Additional information

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

In a bacterial reverse gene mutation assay conducted according to OECD guideline 471, strains TA98, TA100, TA102, TA1535 and TA1537 of Salmonella typhimurium were exposed to 5’-O-[bis(4-methoxyphenyl)phenylmethyl]-2’-deoxythymidine, 3’-[2-cyanoethyl N,N-bis(1-methylethyl)phosphoramidite] (99.7% purity) in DMSO at concentrations of 31.6, 100, 316, 1000, 2500 and 5000 µg/plate in the presence and absence of mammalian metabolic activation. The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background in all tester strains in both experiments (plate incorporation and pre-incubation). Based on the results, the test item is considered to be non-mutagenic in the bacterial reverse gene mutation assay.

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 mutagenicity.