Cyclohexylidenebis[tert-amyl] peroxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

in silico

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:

See enclosed files

Data source

Reference

Reference 1

Reference Type:

publication

Title:

pkCSM: predicting small-molecule pharmacokinetic properties using graph-based signatures

Author:

Pires DEV, Blundell TL and Ascher DB

Year:

2015

Bibliographic source:

Journal of Medicinal Chemistry, 58 (9):4066–4072

Reference 2

Reference Type:

other: web site

Title:

Unnamed

Year:

2018

Materials and methods

Objective of study:

absorption

distribution

excretion

metabolism

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on IR&CSA, Chapter R.14, Occupational exposure assessment Update to change the scope of the guidance from exposure estimation to exposure assessment

Version / remarks:

August 2016

Principles of method if other than guideline:

pkCSM uses graph-based signatures to develop predictive models of central ADME properties. pkCSM performs as well or better than current methods.

Test material

Test material information

Constituent 1

Reference substance name:

Cyclohexylidenebis[tert-amyl] peroxide

EC Number:

239-741-1

EC Name:

Cyclohexylidenebis[tert-amyl] peroxide

Cas Number:

15667-10-4

Molecular formula:

C16H32O4

IUPAC Name:

1,1-bis[(2-methylbutan-2-yl)peroxy]cyclohexane

Details on test material:

IUPAC Name: 1,1-bis(2-methylbutan-2-ylperoxy)cyclohexane
Canonical SMILES: CCC(C)(C)OOC1(CCCCC1)OOC(C)(C)CC
Molecular Formula: C16H32O4
Molecular Weight: 288.428 g/mol

Specific details on test material used for the study:

SMILES:
O(OC(C)(C)CC)C1(OOC(C)(C)CC)CCCCC1

Results and discussion

Main ADME results

Main ADME results 1

Type:

absorption

Results:

Intestinal absorption (human): 92.784%

Main ADME results 2

Type:

distribution

Results:

VDss (human) (log L/kg): 0.242

Main ADME results 3

Type:

distribution

Results:

Fraction unbound (human) : 0.382

Main ADME results 4

Type:

distribution

Results:

BBB permeability (log BB): 0.571

Main ADME results 5

Type:

distribution

Results:

CNS permeability (log PS): -3.485

Main ADME results 6

Type:

excretion

Results:

Total Clearance (log ml/min/kg): 1.602

Main ADME results 7

Type:

excretion

Results:

Renal OCT2 substrate: no

Any other information on results incl. tables

Property	Model Name	Predicted Value	Unit
Absorption	Water solubility	-3.929	Numeric (log mol/L)
Absorption	Caco2 permeability	1.776	Numeric (log Papp in 10^-6cm/s)
Absorption	Intestinal absorption (human)	92.784	Numeric (% Absorbed)
Absorption	Skin Permeability	-2.386	Numeric (log Kp)
Absorption	P-glycoprotein substrate	No	Categorical (Yes/No)
Absorption	P-glycoprotein I inhibitor	No	Categorical (Yes/No)
Absorption	P-glycoprotein II inhibitor	No	Categorical (Yes/No)
Distribution	VDss (human)	0.242	Numeric (log L/kg)
Distribution	Fraction unbound (human)	0.382	Numeric (Fu)
Distribution	BBB permeability	0.571	Numeric (log BB)
Distribution	CNS permeability	-3.485	Numeric (log PS)
Metabolism	CYP2D6 substrate	No	Categorical (Yes/No)
Metabolism	CYP3A4 substrate	No	Categorical (Yes/No)
Metabolism	CYP1A2 inhibitior	No	Categorical (Yes/No)
Metabolism	CYP2C19 inhibitior	No	Categorical (Yes/No)
Metabolism	CYP2C9 inhibitior	No	Categorical (Yes/No)
Metabolism	CYP2D6 inhibitior	No	Categorical (Yes/No)
Metabolism	CYP3A4 inhibitior	No	Categorical (Yes/No)
Excretion	Total Clearance	1.602	Numeric (log ml/min/kg)
Excretion	Renal OCT2 substrate	No	Categorical (Yes/No)