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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption, other
Remarks:
in silico
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Study period:
October 11, 2012
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method

Data source

Referenceopen allclose all

Reference Type:
other: software
Title:
Unnamed
Year:
2011
Reference Type:
other company data
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guideline
Guideline:
other: ECHA Guidance on information requirements and chemical safety assessment - Chapter R.06: QSARs and grouping of chemicals
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 Deposition Rate 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)].

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Percutaneous absorption
Time point:
4 h
Dose:
Deposition dose: 50000 mg
Parameter:
rate
Remarks:
absorbed
Absorption:
<= 0 mg cm-2 h-1

Any other information on results incl. tables

Substance

EC name: tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate

CAS number: 3319-31-1

Molecular weight: 546.78

Temperature: 25 °C

Vapour Pressure: 6.8E-08 Pa

Water solubility: 3.06E-03 mg/L

Log Kow (skin, pH= 5.5): 8.0

Density: 988.5 mg/cm3

 

Scenario parameters

Instantaneous deposition

·        Deposition dose: 50000 mg (max. capacity of skin surface, equal to 25x affected skin)

·        Affected skin area: 2000 cm2 (hands and forearms surface)

 

Timing parameters

·        Start deposition: 0 hr

·        End time observation: 4 hr

 

Report parameters

·        Calculation intervals/hours: 10000 hr

·        Report intervals/hours: 1 hr

 

RESULTS

Deposition: Instantaneous

Tot. Deposition: 50000 mg

 

Fraction absorbed: 0.0%

Amount absorbed: 8.27E-03 mg

Lag time stratum corneum: 117.4 min.

 

Max. derm. abs.: 1E-06 mg/cm2/hr

Max. derm. abs. for 2000 cm2 in 1 hour (from liquid): 2.07E-03 mg

 

Dermal/Respiratory uptake ratio (from airborne vapour): R= 0.858

 

R= RX/X

 RX: total dermal absorption by dermal exposure to airborne vapour

X:  total inhalation absorption from airborne vapour

 

Assuming that Fully Respiratory Protection provides 100% efficiency:

Protection from respirator= 100*X/(RX+X)= 100/(R+1)= 100/1.858= 53.8% protection against overexposure to the substance in the form of vapour due to dermal vapour absorption over whole body surface.

Applicant's summary and conclusion

Conclusions:
The dermal absorption of the test material leads to the following results, obtained using the SkinPerm v1.03 model according to the input data:

Fraction absorbed: 0.0%
Amount absorbed: 8.27E-03 mg
Lag time stratum corneum: 117.4 min.

Max. derm. abs.: 1E-06 mg/cm2/hr
Max. derm. abs. for 2000 cm2 in 1 hour (from liquid): 2.07E-03 mg

Dermal/Respiratory uptake ratio (from airborne vapour): R= 0.858
Executive summary:

In-silico evaluation of dermal absorption indicates that after 4 hours the deposited substance is not absorbed within viable epidermis and therefore can not enter in systemic circulation.