Trimethyl benzene-1,2,4-tricarboxylate

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:

April 18, 2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

accepted calculation method

Justification for type of information:

See the attached justification.

Data source

Reference

Reference 1

Reference Type:

other: software

Title:

IH SkinPerm v2.04

Author:

AIHA Exposure Assessment Strategies Committee (EASC) and the Dermal Project Team (DPT) in collaboration with Wil ten Berg

Year:

2017

Bibliographic source:

Tibaldi, R., ten Berge, W., Drolet, D.. IH SkinPerm v2.0 Reference Manual. https://www.aiha.org/get-involved/VolunteerGroups/Documents/IH_SkinPerm_Manual_May_2017.pdf

Reference 2

Reference Type:

other company data

Title:

Unnamed

Year:

2018

Report date:

2018

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:

See the justification for type of information.

Test material

Test material information

Constituent 1

Reference substance name:

Trimethyl benzene-1,2,4-tricarboxylate

EC Number:

219-547-3

EC Name:

Trimethyl benzene-1,2,4-tricarboxylate

Cas Number:

2459-10-1

Molecular formula:

C12H12O6

IUPAC Name:

1,2,4-trimethyl benzene-1,2,4-tricarboxylate

Results and discussion

Percutaneous absorption

Time point:

2 h

Dose:

Deposition dose: 6060 mg

Parameter:

rate

Absorption:

<= 0.001 mg cm-2 h-1

Any other information on results incl. tables

DATA INPUT

Substance

EC name: trimethyl benzene-1,2,4-tricarboxylate

CAS number: 2459-10-1

Molecular weight: 252.22

Temperature: 25°C

Vapour Pressure: 0.0033 Pa

Water solubility: 1110 mg/L

Log Kow (skin, pH= 5.5): 1.96

Density: 1263 mg/cm³

Melting Point: 25°C

Scenario parameters

Instantaneous deposition

Deposition dose^*: 6062 mg

Affected skin area^**: 1000 cm²

Maximum skin adherence^**: 1.5 mg/cm²

Thickness of stagnant air^***: 1 cm

Weight fraction: 1

Timing parameters

Start deposition: 0 hr

End time observation: 2 hr

Report parameters

Calculationintervals/hours: 7200

Report intervals/hours: 120

* 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. It is reasonably expected more liquid will be excess and wash/fall off.

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

*** Nude skin.

RESULTS

Fraction absorbed: 0.098%

Amount absorbed: 5.95 mg

Lag time stratum corneum:74.6 min.

 

Max. derm. abs.: 0.00149 mg/cm2/hr

Max. derm. abs. for 2000 cm2in 1 hour (from liquid): 2.99 mg

 

Dermal/Respiratory uptake ratio (from airborne vapour): R= 1.25

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) = 100/2.25 = 44.4%

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 trimethyl benzene-1,2,4-tricarboxylate leads to the following results, obtained using the SkinPerm v2.04 model according to the input data:

Fraction absorbed: 0.098%
Amount absorbed: 5.95 mg
Lag time stratum corneum: 74.6 min.

Max. derm. abs.: 0.0149 mg/cm2/hr
Max. derm. abs. for 2000 cm2 in 1 hour (from liquid): 2.99 mg

Dermal/Respiratory uptake ratio (from airborne vapour): R= 1.25

Executive summary:

In-silico evaluation of dermal absorption shows that after 2 hours only ca. 6 mg. of deposited substance are absorbed within viable epidermis and therefore could enter in systemic circulation.