Methanone, 1,1'-(1,4-phenylene)bis[1-(4-phenoxyphenyl)-

Endpoint summary

Link to relevant study record(s)

Reference

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

Qualifier:

according to guideline

Guideline:

other: REACH Guidance on QSARs R.6

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

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.

Species:

other: human

Type of coverage:

open

Vehicle:

unchanged (no vehicle)

Details on study design:

DATA INPUT
Molecular weight: 470.52 g/mol
Temperature: 25 °C
Vapour Pressure: 0.000001 Pa
Water solubility: 0.005 mg/L
Log Kow: 8.41
Density: 1340 mg/cm3
Melting point: 215.2°C

SCENARIO PARAMETERS
- Instantaneous deposition
Deposition dose*: 1000 mg
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
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 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

Time point:

8 h

Dose:

1000 mg

Parameter:

percentage

Absorption:

0.018 %

Remarks on result:

other: Instantaneous deposition

Time point:

8 h

Dose:

1 mg/cm²/h

Parameter:

percentage

Absorption:

0.018 %

Remarks on result:

other: Deposition over time for 8 hr

Conclusions:

EKKE is estimated to be not absorbed by dermal route

Executive summary:

The dermal absorption of EKKE 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 (%)	0.018	0.018
Amount absorbed (mg)0.	0.179	0.179
Lag time stratum corneum (min)	26.6
Max. derm. abs. (mg/cm²/h)	0.0000112

Description of key information

EKKE is a powder insoluble in water (< 5 µg/L) and has a very low solubility in organic solvents like octanol (ca. 4 mg/L). Therefore, the oral, pulmonary absorption is expected to be very low, as confirmed by the lack of systemic toxicity observed in the repeated dose toxicity studies by oral or inhalation routes. The absorption by the dermal route is also expected by be very low (0.018%) based on the estimation performed by the IHSkinPerm model.