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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

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Administrative data

Link to relevant study record(s)

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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 drug in that environment.
Species:
other: Human
Type:
absorption
Results:
Absorption from gastrointestinal tract for 1 mg dose: 100%
Type:
absorption
Results:
Absorption from gastrointestinal tract for 1000 mg dose: 90%
Executive summary:

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.

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 valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Guideline:
other: REACH Guidance on QSARs R.6
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:
IH SkinPerm (v2.04) 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.
IH Skin Perm provides two primary dermal exposure modes to the modeler. The first is “instantaneous deposition” in which the substance is assumed to be on the skin as the result of a single exposure event. The second is “deposition over time” in which the substance is assumed to be applied at a constant rate over time. In the first case (instantaneous deposition) the above DepositionRate is zero and IH Skin Perm then works to keep track of this single dose over time as it is absorbed into the SC or evaporates from the surface of the skin. In the second case (deposition over time) the rate of the substance going to the skin is assumed constant and the thickness of the film on the skin will either increase or decrease with time depending on the relative rates of deposition and removal.
The user inputs the amount going onto the skin as a single dose or as a constant rate and IH SkinPerm calculates the amount of chemical absorbed into the SC over time until all the material disappears from the surface via absorption and evaporation or the exposure is considered to be over.
Ultimately, the program estimates the amount of chemical absorbed into the systemic circulation of the body using clearly defined assumptions.
IH SkinPerm does all of this using relatively few physical chemical inputs for the substance. The details of these calculations are all available from Dr. ten Berge (ref: specific documents in attached justification section).
Species:
other: human
Type of coverage:
open
Vehicle:
unchanged (no vehicle)
Details on study design:
DATA INPUT
Molecular weight: 338.48 g/mol
Temperature: 20 °C
Vapour Pressure: 0.00012 Pa
Water solubility: 0.04 mg/L
Log Kow: 7.3
Density: 970 mg/cm3
Melting point: 37°C

SCENARIO PARAMETERS
- Instantaneous deposition
Deposition dose*: 1000 mg
Affected skin area**: 1000 cm²
Maximum skin adherence***: 0.1 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***: 0.1 mg/cm²#
Dermal deposition rate: 1 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
Report parameters
. Calculation (intervals/hr): 10000
. Report (intervals/hr): 100

*Default value defined according to the internal validation study
**Estimated skin surface of two hands of an adult.
***The maximum skin adherence refers to the substance mass per cm2 that can physically stay on the skin. This may be referenced in the literature or estimated. The maximum for solids is 3 mg/cm2 and for liquids 10 mg/cm2. If the instantaneous deposition is larger than the maximum skin adherence, the surplus is assumed to get lost.
*** 3 cm if clothing involved, 1 cm if bare skin involved
# [1,3 (or 1,4)-Phenylenebis(1-methylethylidene)]bis[ter-butyl]peroxide appears in the form of big compact blocks (92% of the test item) and powder (8% of the test item). 7% of particles present a mean diameter of 214µm, and only 0.75% of particles present a mean diameter lower than 100µm (99µm). Under standard conditions the skin adherence will be limited.

Time point:
8 h
Dose:
1000 mg
Parameter:
percentage
Absorption:
10 %
Remarks on result:
other: Instantaneous deposition
Time point:
8 h
Dose:
1 mg/cm²/h
Parameter:
percentage
Absorption:
4.8 %
Remarks on result:
other: Deposition over time for 8 hr
Conclusions:
The dermal absorption of Luperox F ([1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[tert-butyl] peroxide) is estimated to be low (<= 10%).
Executive summary:

The dermal absorption of Luperox F ([1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[tert-butyl] peroxide) leads to the following results, obtained using the SkinPerm v2.04 model according to the input data:

 

Instantaneous deposition

 

Deposition over time

End time observation 8 hr

Total deposition (mg) or deposition rate (mg/cm²/hr)

1000

1

Fraction absorbed (%)

10

4.8

Amount absorbed (mg)

1.76

Lag time stratum corneum (min)

7.21

Max. derm. abs. (mg/cm²/h)

0.00011

Description of key information

No data on toxicokinetics, metabolism and distribution are available for [1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[tert-butyl] peroxide.

Absorption

The assessment of the toxicokinetics of [1,3(or 1,4)-phenylenebis(1-methylethylidene)]bis[tert-butyl] peroxide is based on the available toxicological data and its physicochemical properties as suggested by the REACH Guidance Chapter R.7c.

The product appears in the form of big compact blocks and powder (8% of the test item with a mean diameter of 214 µm) at room temperature. The molecular weight is 338.48 g/mol for the meta and para isomers. The substance is poorly in water (0.04 mg/L) and has a very low vapor pressure (0.00012 Pa at 20 °C). The logKow of both meta and para isomers is estimated at 7.3 and a logBCF of 3.96 was calculated.

 

Dermal absorption

Based on its physico–chemical properties, the substance is not likely to penetrate skin to a large extent as it is a compact solid, nearly insoluble in water and with a Log Kow not in favor of dermal uptake. Therefore, the rate of absorption was estimated using the IH SkinPerm model v2.04). For an instantaneous skin deposition of 1000 mg or a deposition over time of 1mg/cm²/h for 8 h, the absorption rates after 8 hours were estimated to be 10 and 4.8%, respectively. The low absorption rate is further supported by the acute dermal toxicity study results. Moreover the substance is not a skin irritant; therefore no increase of skin absorption is expected.

 

Oral absorption

Based on the low solubility in water and its high lipophilic properties, the substance could be absorbed in a large extent following oral exposure. 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. The high absorption rate is further supported by the repeated oral toxicity study results.

 

Inhalation exposure

Based on the very low vapor pressure and on the high granulometry of the powder fraction, inhalation exposure is unlikely. However, if exposed, it is likely the substance will also be absorbed.

Therefore, according to the REACH Guidance, default values of 100, 10 and 100% will be used for oral, dermal and inhalation absorptions, respectively.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
100
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information