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Diss Factsheets

Administrative data

Endpoint:
dermal absorption, other
Remarks:
in silico
Type of information:
(Q)SAR
Remarks:
IH Skin Perm
Adequacy of study:
key study
Study period:
June 2016
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:
Estimation method using accepted and valid (Q)SAR method.

Data source

Reference
Reference Type:
other: Software
Title:
IH Skin Perm
Year:
2016

Materials and methods

Principles of method if other than guideline:
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 (http://home.planet.nl/~wtberge/qsarperm.html).
GLP compliance:
no
Remarks:
Computer model

Test material

Constituent 1
Chemical structure
Reference substance name:
Tetrakis(2-ethylhexyl) benzene-1,2,4,5-tetracarboxylate
EC Number:
221-508-0
EC Name:
Tetrakis(2-ethylhexyl) benzene-1,2,4,5-tetracarboxylate
Cas Number:
3126-80-5
Molecular formula:
C42H70O8
IUPAC Name:
1,2,4,5-tetrakis(2-ethylhexyl) benzene-1,2,4,5-tetracarboxylate
Test material form:
liquid: viscous
Specific details on test material used for the study:
CAS 3126-80-5
EC 221-508-0
Molecular weight: 703
Temperature: 25 °C
Vapour Pressure:
Water solubility:
Log Kow (skin, pH= 5.5):
Density: 988.5 mg/cm3 (exp.)

Results and discussion

Percutaneous absorptionopen allclose all
Key result
Time point:
1 h
Dose:
1 mg/cm-2/h to 2000 cm-2 skin area
Parameter:
rate
Absorption:
0 mg cm-2 h-1
Key result
Time point:
1 h
Dose:
1 mg/cm-2/h to 2000 cm-2 skin area
Parameter:
amount
Absorption:
0.002 other: mg
Key result
Time point:
1 h
Dose:
of 1 mg/cm-2/h to 2000 cm-2 skin area
Parameter:
percentage
Absorption:
0 %

Applicant's summary and conclusion

Conclusions:
Absorbed fraction: 0.0000824%
Amount absorbed: 0.00165 mg
Maximum dermal absorption: 1.03 x 10-6 mg/cm2/h
Dermal/respiratory uptake ratio (from airborne vapor): 0.032

The dermal absorption of tetrakis(2-ethylhexyl) benzene-1,2,4,5-tetracarboxylate is expected to be negligible.
Executive summary:

The dermal absorption of the test item was calculated with IH SkinPerm model of dermal absorption (v. 2.0) as provided by the American Industrial Hygiene Association (AIHA): Calculation of the absorbed fraction as a result of dermal deposition at a rate of 1 mg/cm2/h to 2000 cm2skin area (hands and forearms) during 1 h. The calculation is based on molecular weight of 702.5 g/mol, vapor pressure of 0.00209 Pa (MPBPWIN™ by EPI Suite v.4.1), water solubility of 1 mg/L (exp.), an octanol-water partition coefficient of Log Po/w 6.01 (exp.), density of 0.9908 mg/cm3(exp.) and a melting point of -34 °C (exp.) of the test item.

The calulated values are as follows:

Absorbed fraction: 0.0000824%

Amount absorbed: 0.00165 mg

Maximum dermal absorption: 1.03 x 10-6mg/cm2/h

Dermal/respiratory uptake ratio (from airborne vapor): 0.032

The dermal absorption of tetrakis(2-ethylhexyl) benzene-1,2,4,5-tetracarboxylate is negligible and the compound is expected to be not systemically bioavailable after dermal exposure .