Butyl 4,4-bis(tert-butyldioxy)valerate

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics, other

Remarks:

G.I. human passive absorption

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Objective of study:

absorption

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

Model to predict either high or low fraction absorbed for an orally administered, passively transported substance on the basis of a new absorption parameter. The model includes only two inputs: the octanol-water partition coefficient (Kow) and the dimensionless oversaturation number (OLumen). The latter is the ratio of the concentration of drug delivered to the gastro-intestinal (GI) fluid to the solubility of the compound in that environment.

Specific details on test material used for the study:

SMILES (used for QSAR prediction): C(=O)(CCC(C)(OOC(C)(C)C)OOC(C)(C)C)OCCCC

Species:

other: Human

Route of administration:

oral: unspecified

Type:

absorption

Results:

Absorption from gastrointestinal tract for 1 mg dose: 100%

Type:

absorption

Results:

Absorption from gastrointestinal tract for 1000 mg dose: 90%

Reference 2

Endpoint:

dermal absorption, other

Remarks:

Mathematical simulation

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

IH SkinPerm mathematical tool for estimating dermal absorption

Time point:

8 h

Dose:

1000 mg

Parameter:

percentage

Remarks:

Instantaneous deposition

Absorption:

0 %

Time point:

8 h

Dose:

1 mg/cm²/h

Parameter:

percentage

Remarks:

Deposition over time

Absorption:

0 %

Reference 3

Endpoint:

dermal absorption, other

Remarks:

QSAR

Type of information:

(Q)SAR

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a (Q)SAR model, with limited documentation / justification, but validity of model and reliability of prediction considered adequate based on a generally acknowledged source

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

The Dermal Permeability Coefficient Program (DERMWIN) v2.00 estimates the dermal permeability coefficient (Kp), the dermally absorbed dose per event (DAevent) and Dermal Absorbed Dose (DAD) of organic compounds via water contact.

Specific details on test material used for the study:

SMILES : C(=O)(CCC(C)(OOC(C)(C)C)OOC(C)(C)C)OCCCC

Parameter:

rate

Remarks:

Kp

Absorption:

0.384 cm/h

Remarks on result:

other:

                 Kp (est): 0.384 cm/hr

SMILES : O=C(CCC(C)(OOC(C)(C)C)OOC(C)(C)C)OCCCC

CHEM   : butyl 4,4-bis(tert-butyldioxy)valerate

MOL FOR: C17 H34 O6

MOL WT : 334.46

------------------------------ Dermwin v2.01 ----------------------------------

Log Kow  (estimated)  :  6.42

Log Kow (experimental):  not available

GENERAL Equation:   log Kp = -2.80 + 0.66 log Kow - 0.0056 MW

   Kp (predicted): 3.84e-001  cm/hr

Dermally Absorbed Dose per Event for Organic Compounds - Water Contact:

  Water Conc (mg/cm3): 2.5e-005  (estimated by program)

  Fraction Absorbed  : 1.0000

  DA(event):  5.79e-005 mg/cm2-event (using eqn 3.2 & 3.3)

                  (tau = 8.01 hr,  t* = 33.6 hr)

Dermally Absorbed Dose (70 kg Adult) - Water Contact:

  DAD:  6.12e-003 mg/kg-day (using eqn 3.1)

Description of key information

There is no experimental data on toxicokinetic.

Butyl 4,4-bis(tert-butyldioxy)valerate has a molecular weight of 334 g/mol, a low solubility in water 2.16 mg/L at 20°C and an experimental log Ko/w of 6.34.

Absorption

According to the REACH Guidance, default values of 100, 10 and 50% will be used for oral, dermal and inhalation absorptions of butyl 4,4-bis(tert-butyldioxy)valerate, respectively.

Oral absorption

Oral absorption is favored for molecular weights below 500 g/mol. Based on the log Ko/w of 6.34, butyl 4,4-bis(tert-butyldioxy)valerate can be regarded as a lipophilic substance. Such a lipophilic compound may be taken up by micellular solubilisation. Using a model to predict either high or low fraction absorbed for an orally administered, passively transported substance, the rates of absorption were 100 and 90% for a dose of 1 and 1000 mg, respectively (Danish QSAR database).

Dermal absorption

Between water solubility of 1-100 mg/l dermal absorption is anticipated to be low to moderate. With a log Ko/w above 6, the rate of transfer between the stratum corneum and the epidermis will be slow and will limit absorption across the skin. Uptake into the stratum corneum itself may be slow.

The rate of absorption was estimated using the IH SkinPerm model using a Kp derived from the EPI Dermwin model. For a continuous skin deposition of 1 mg/cm²/h for 8 h or an instantaneous deposition of 1000 mg, butyl 4,4-bis(tert-butyldioxy)valerate is not expected to be absorbed (0%).

Metabolism and excretion:

There is no data on butyl 4,4-bis(tert-butyldioxy)valerate metabolism.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

50