Vinyl ethylene carbonate

Basic toxicokinetics

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

Test material information

Constituent 1

Reference substance name:

Vinyl ethylene carbonate

EC Number:

700-261-7

Cas Number:

4427-96-7

Molecular formula:

C5H6O3

IUPAC Name:

Vinyl ethylene carbonate

Test material form:

liquid

Specific details on test material used for the study:

SMILES: O1C(=O)OC(C1)C=C

Applicant's summary and conclusion

Executive summary:

 

ADME	Profiles	Predicted results	Unit	Interpretation
Absorption	Pgp-inh	0.0	-	Non-inhibitor
	Pgp-sub	0.001	-	Non-substrate
	HIA	0.004	-	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	-4.543	log cm/s	The predicted Caco-2 permeability is excellent (> -5.15 log cm/s).
	MDCK	0.00018	cm/s	The predicted MDCK permeability is excellent (> 2E-05 cm/s).
Distribution	BBB	0.998	-	The predicted of BBB penetration is more than 0.1 cm/s (BBB+).
	PPB	28.06%	-	The predicted Plasma protein binding is excellent (<= 90%).
	VD	0.659	L/kg	The predicted Volume Distribution is excellent (0.04-20 L/kg).
	Fu	73.60%	-	The predicted Fraction unbound in plasms is > 20% (High Fu).
Metabolism	CYP1A2-inh	0.089	-	Non-inhibitor
	CYP1A2-sub	0.298	-	Non-substrate
	CYP2C19-inh	0.057	-	Non-inhibitor
	CYP2C19-sub	0.645	-	Non-substrate
	CYP2C9-inh	0.011	-	Non-inhibitor
	CYP2C9-sub	0.152	-	Non-substrate
	CYP2D6-inh	0.008	-	Non-inhibitor
	CYP2D6-sub	0.611	-	Non-substrate
	CYP3A4-inh	0.132	-	Non-inhibitor
	CYP3A4-sub	0.314	-	Non-substrate
Excretion	CL	8.31	ml/min/kg	The clearance of target chemical is moderate clearance (5-15 ml/min/kg).
	T1/2	0.848	-	The predicted T1/2 > 3h