tert-butyl α,α-dimethylbenzyl peroxide

Dermal absorption

Administrative data

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

Data source

Reference

Reference 1

Title:

IH SkinPerm (v2.04)

Author:

AIHA

Year:

2018

Bibliographic source:

https://www.aiha.org/get-involved/VolunteerGroups/Pages/Exposure-Assessment-Strategies-Committee.aspx

Reference 2

Reference Type:

publication

Title:

Dermal absorption of chemicals: estimation by IH SkinPerm

Author:

Tibaldi R, ten Berge W, Drolet D

Year:

2014

Bibliographic source:

J Occup Environ Hyg.,11(1):19-31

Materials and methods

Test guideline

Guideline:

other: REACH Guidance on QSARs R.6

Principles of method if other than guideline:

IH SkinPerm (v2.0) is a mathematical tool for estimating dermal absorption. The rate of mass build-up (or loss) on the skin comes from the deposition rate onto the skin minus the absorption rate into the Stratum Corneum (SC) and the amount evaporating from the skin to the air.

Test material

Test material information

Constituent 1

Reference substance name:

tert-butyl α,α-dimethylbenzyl peroxide

EC Number:

222-389-8

EC Name:

tert-butyl α,α-dimethylbenzyl peroxide

Cas Number:

3457-61-2

Molecular formula:

C13H20O2

IUPAC Name:

[2-(tert-butylperoxy)propan-2-yl]benzene

Details on test material:

SMILES: CC(C)(C)OOC(C)(C)C1=CC=CC=C1
Molecular Formula: C13 H20 O2
Molecular weight (g/mole): 208.3

Test animals

Species:

other: human

Administration / exposure

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on study design:

DATA INPUT
Molecular weight: 208.3 g/mol
Temperature: 25 °C
Vapour Pressure: 3 Pa (Epiwin)
Water solubility: 10.7 mg/L
Log Kow: 4.47
Density: 963.2 mg/cm3
Melting point: 11.3°C

SCENARIO PARAMETERS
- Instantaneous deposition
Deposition dose*: 4493 mg (4.8 mL * density mg/cm3)
Affected skin area**: 1000 cm²
Maximum skin adherence***: 2 mg/cm²
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. End time observation: 8 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

- Deposition over time
Affected skin area**: 1000 cm²
Maximum skin adherence***: -1 mg/cm²
Dermal deposition rate: 2 mg/cm²/hr
Thickness of stagnant air****: 1 cm
Weight fraction: 1
Timing parameters
. Start deposition: 0 hr
. Duration of deposition: 8hr
. End time observation: 8 hr and 24 hr
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

*Approximately 2 mL of a liquid having a viscosity similar to water will practically wet the palms of two hands (420 cm2). So ca. 4.8 mL will wet all the skin surface of both hands. It is reasonably expected more liquid will be excess and wash/fall off.)
**Estimated skin surface of two hands of an adult.
***The skin adherence field is greyed out and a default of -1 is indicated if the substance is a liquid at 25°C. Smart logic is built into IH SkinPerm; the program recognizes whether a substance is a solid or liquid at standard temperature (25°C) based on the physicochemical properties. For substances
that are solids at 25°C a maximum adherence value up to 2 mg/cm² is allowed based on studies of soil-on-skin adherence. If the deposition rate results in an increase above the input figure (0.2-2 mg/cm²), it is assumed that the surplus disappears just by removal from the skin.
*** 3 cm if clothing involved, 1 cm if bare skin involved

Results and discussion

Percutaneous absorption

Percutaneous absorption 1

Time point:

8 h

Dose:

4493 mg/1000cm²/8hr

Parameter:

percentage

Absorption:

0.61 %

Remarks on result:

other: Instantaneous deposition

Percutaneous absorption 2

Time point:

8 h

Dose:

1 mg/cm²/h

Parameter:

percentage

Absorption:

0.34 %

Remarks on result:

other: Deposition over time for 8 hr

Percutaneous absorption 3

Time point:

24 h

Dose:

1 mg/cm²/h

Parameter:

percentage

Absorption:

1.03 %

Remarks on result:

other: Deposition over time for 8 hr

Applicant's summary and conclusion

Conclusions:

The dermal absorption of tert-butyl 1-methyl-1-phenylethyl peroxide is estimated to be loiw (<= 1%).

Executive summary:

The dermal absorption of tert-butyl 1-methyl-1-phenylethyl peroxide leads to the following results, obtained using the SkinPerm v2.0 model according to the input data:

	Instantaneous deposition	Deposition over time End time observation 8 hr	Deposition over time End time observation 24hr
Total deposition (mg)	4490	8000	8000
Fraction absorbed (%)	0.611	0.343	1.03
Amount absorbed (mg)	27.5	27.5	82.4
Lag time stratum corneum (min)	6.97	6.97	6.97
Max. derm. abs. (mg/cm²/h)	0.00172	0.00172	0.00172