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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics, other
Type of information:
(Q)SAR
Adequacy of study:
key study
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 limited documentation / justification
Justification for type of information:
1. SOFTWARE
ADMETlab 2.0

2. MODEL (incl. version number)
ADMETlab 2.0

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
SMILES: O1C(=O)OC(C1)C=C

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
[[Explain how the model fulfils the OECD principles for (Q)SAR model validation. Consider attaching the QMRF and/or QPRF or providing a link]
- Defined endpoint:
1) Absorption:
Caco-2 Permeability, MDCK Permeability, Pgp-inhibitor, Pgp-substrate, HIA, F20%, F30%
2) Distribution:
PPB, VD, BBB Penetration, Fu
3) Metabolism:
CYP 1A2 / 2C19 / 2C9 / 2D6 / 3A4 inhibitor, CYP 1A2 / 2C19 /2C9 / 2D6 / 3A4 substrate
4) Excretion
CL, T1/2

- Unambiguous algorithm:
Multi-task graph attention (MGA) framework

- Defined domain of applicability:

- Appropriate measures of goodness-of-fit and robustness and predictivity:
Please see the attachment "ADMETlab 2.0_an integrated online platform for accurate and comprehensive predictions of ADMET properties" Table 1 and Table 2.

- Mechanistic interpretation:
Please see the attachment "ADMETlab 2.0_an integrated online platform for accurate and comprehensive predictions of ADMET properties"

5. APPLICABILITY DOMAIN
[Explain how the substance falls within the applicability domain of the model]
- Descriptor domain:
- Structural domain:
- Mechanistic domain:
- Similarity with analogues in the training set:
- Other considerations (as appropriate):

6. ADEQUACY OF THE RESULT
[Explain how the prediction fits the purpose of classification and labelling and/or risk assessment]

Data source

Reference
Reference Type:
other: QSAR
Title:
Unnamed
Year:
2022

Materials and methods

Test material

Constituent 1
Chemical structure
Reference substance name:
(4R)-4-ethenyl-1,3-dioxolan-2-one; (4S)-4-ethenyl-1,3-dioxolan-2-one
EC Number:
700-261-7
Cas Number:
4427-96-7
Molecular formula:
C5H6O3
IUPAC Name:
(4R)-4-ethenyl-1,3-dioxolan-2-one; (4S)-4-ethenyl-1,3-dioxolan-2-one
Test material form:
liquid
Specific details on test material used for the study:
SMILES: O1C(=O)OC(C1)C=C

Results and discussion

Applicant's summary and conclusion

Executive summary:

 













































































































































































ADMEProfilesPredicted resultsUnitInterpretation
AbsorptionPgp-inh0.0-Non-inhibitor
 Pgp-sub0.001-Non-substrate
 HIA0.004-The predicted human intestinal absorption is more than 30%.
 F(20%)0.038-The predicted human oral bioavailability is more than 20%.
 F(30%)0.949-The predicted human oral bioavailability is less than 30%.
 Caco-2-4.543log cm/sThe predicted Caco-2 permeability is excellent (> -5.15 log cm/s).
 MDCK0.00018cm/sThe predicted MDCK permeability is excellent (> 2E-05 cm/s).
DistributionBBB0.998-The predicted of BBB penetration is more than 0.1 cm/s (BBB+).
 PPB28.06%-The predicted Plasma protein binding is excellent (<= 90%).
 VD0.659L/kgThe predicted Volume Distribution is excellent (0.04-20 L/kg).
 Fu73.60%-The predicted Fraction unbound in plasms is > 20% (High Fu).
MetabolismCYP1A2-inh0.089-Non-inhibitor
 CYP1A2-sub0.298-Non-substrate
 CYP2C19-inh0.057-Non-inhibitor
 CYP2C19-sub0.645-Non-substrate
 CYP2C9-inh0.011-Non-inhibitor
 CYP2C9-sub0.152-Non-substrate
 CYP2D6-inh0.008-Non-inhibitor
 CYP2D6-sub0.611-Non-substrate
 CYP3A4-inh0.132-Non-inhibitor
 CYP3A4-sub0.314-Non-substrate
ExcretionCL8.31ml/min/kgThe clearance of target chemical is moderate clearance (5-15 ml/min/kg).
 T1/20.848-The predicted T1/2 > 3h