Benzene-1,2,4-tricarboxylic acid 1,2-anhydride

Dermal absorption

Administrative data

Endpoint:

dermal absorption, other

Remarks:

in silico

Type of information:

calculation (if not (Q)SAR)

Adequacy of study:

key study

Study period:

February 26, 2016

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Data source

Reference

Reference 1

Reference Type:

other: software

Title:

Unnamed

Year:

2014

Reference 2

Reference Type:

other company data

Title:

Unnamed

Year:

2016

Report date:

2016

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

Test material information

Constituent 1

Reference substance name:

Benzene-1,2,4-tricarboxylic acid

EC Number:

208-432-3

EC Name:

Benzene-1,2,4-tricarboxylic acid

Cas Number:

528-44-9

Molecular formula:

C9H6O6

IUPAC Name:

benzene-1,2,4-tricarboxylic acid

Results and discussion

Percutaneous absorption

Time point:

4 h

Dose:

Deposition dose: 7939 mg

Parameter:

rate

Remarks:

absorbed

Absorption:

<= 0.001 mg cm-2 h-1

Any other information on results incl. tables

DATA INPUT

Substance

EC name: benzene-1,2,4-tricarboxylic acid

CAS number: 528-44-9

Molecular weight: 210.14

Temperature: 25°C

Vapour Pressure: 1.4E-06 Pa

Water solubility: 24400 mg/L

Log Kow (skin, pH= 5.5): -3.34

Density: 1654 mg/cm³(published data)

 

Scenario parameters

Instantaneous deposition

·       Deposition dose^*: 7939 mg

·       Affected skin area^**: 1000 cm²

·       Thickness of stagnant air^***: 1 cm

 

Timing parameters

·       Start deposition: 0 hr

·       End time observation: 4 hr

 

Report parameters

·       Calculationintervals/hours: 7200

·       Report intervals/hours: 60

 

^* Approximately 2 mL of a liquid having a viscosity similar to water will practically wet the palms of two hands (ca. 420 cm2). So 4.8 mL will wet all the skin surface of both hands. Ii is reasonably expected more liquid will be excess and wash/fall off.

 

^** Estimated skin surface of two hands of an adult.

 

^*** Nude skin.

RESULTS

Deposition: Instantaneous

Tot. Deposition: 7939 mg

End time observation: 4 hr

 

Fraction absorbed: 0.1%

Amount absorbed: 5.8 mg

Lag time stratum corneum: 133.2 min.

 

Max. derm. abs.: 7.33E-04 mg/cm²/hr

Max. derm. abs. for 2000 cm²in 1 hour (from liquid): 1.47 mg

 

Dermal/Respiratory uptake ratio (from airborne vapour): R= 4.157

 

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)= 100/5.157= 19.4% 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 v1.21 model, according to the input data:

Fraction absorbed: 0.1%
Amount absorbed: 5.8 mg
Lag time stratum corneum: 133.2 min.

Max. derm. abs.: 7.33E-04 mg/cm2/hr
Max. derm. abs. for 2000 cm2 in 1 hour (from liquid): 1.47 mg

Dermal/Respiratory uptake ratio (from airborne vapour): R= 4.157

Executive summary:

In-silico evaluation of dermal absorption indicates that after 4 hours only a very small amount of deposited substance is absorbed within viable epidermis and therefore enter in systemic circulation.