methyl 7-chloro-6,7,8-trideoxy-3,4-O-isopropylidene-6-{[(4R)-1-methyl-4-propyl-L-propyl]amino}-1-thio-L-threo-α-D-galacto-octopyranoside

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

1. SOFTWARE

-ACD/Percepta

2. MODEL

- Advanced chemistry devlopmnent, INc.; Pharma Algorithms, Inc., Version 2016

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL

O=C(C1N(C)CC(CCC)C1)NC(C2OC(SC)C(O)C3C2OC(C)(C)O3)C(Cl)C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL

This above mentioned tool was selected according to the OECD Guidance Documents on the Validation of (Q)SAR models:

- Document on the validation of (Quantitative) Structure Activity Relationship models. OECD Series on testing and Assessment N° 69. ENV/JM/MONO(2007)2.

5. APPLICABILITY DOMAIN

ACD/Percepta : Reliability Index (RI) from 0 (not reliable) to 1(fully reliable)

6. ADEQUACY OF THE RESULT

ACD/Percepta: oral toxicity on rat: moderate reliable

from the evaluation of result, the target compound was predicted to be orally toxic on rat and the final predisction was assessed as moderate reliable.

Data source

Reference

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD series on testing and assessment n°69

Version / remarks:

ENV/JM/MONO(2007)2

Deviations:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

(2S,4R)-N-[(1S,2S)-1-[(3aS,4R,6R,7R,7aR)-7-hydroxy-2,2-dimethyl-6-(methylsulfanyl)-hexahydro-[1,3]dioxolo[4,5-c]pyran-4-yl]-2-chloropropyl]-1-methyl-4-propylpyrrolidine-2-carboxamide

EC Number:

604-595-3

Cas Number:

147650-54-2

Molecular formula:

C21H37ClN2O5S

IUPAC Name:

(2S,4R)-N-[(1S,2S)-1-[(3aS,4R,6R,7R,7aR)-7-hydroxy-2,2-dimethyl-6-(methylsulfanyl)-hexahydro-[1,3]dioxolo[4,5-c]pyran-4-yl]-2-chloropropyl]-1-methyl-4-propylpyrrolidine-2-carboxamide

Test animals

Species:

rat

Strain:

not specified

Remarks:

this is a (Q)SAR in silico study

Sex:

not specified

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

not specified

Remarks:

this is a (Q)SAR in silico study

Control animals:

not specified

Results and discussion

Effect levels

Sex:

not specified

Dose descriptor:

LD50

Effect level:

ca. 420 other: mg/kg

Based on:

other: (Q)SAR in silico prediction

Any other information on results incl. tables

This study was designed to generate estimated "in silico" (non-testing) data to be used for the hazard assessment of the substance.

The table below shows the result obtained.

Endpoint	Prediction call	Reliability Assessment
Acute oral toxicity (rat)	LD50 = 420 mg/kg	Moderate reliable

Applicant's summary and conclusion

Interpretation of results:

Category 1 based on GHS criteria

Conclusions:

ACUTE ORAL TOXICITY

prediction call: LD50= 420 mg/kg
reliability assesssment: moderate reliable

Executive summary:

The acute oral toxicity of the target compound was predicted employing ACD/Percepta model that provides LD50 predictions for rat by oral administration routes, based on the GALAS methodology. Estimation of the RI takes into account two aspects: similarity of the tested compound to the training and the consistency of experimental values for similar compounds. In the weight of evidence assessment only reliable predictions are to be taken into account. In the case of the target methyl 7-chloro-6,7,8- trideoxy-3,4-O-isopropylidene-6-{[(4R)-1-methyl-4-propyl-L-propyl]amino}-1-thio-L-threo-α-D-galacto-octopyranoside ACD/Percepta provided an LD50 prediction equal to 420 mg/kg so the prediction is assessed as moderate reliable.