5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1-nonanol

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:

January 17, 2019

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:

2019

Report date:

2019

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:

1,2,4-trinonyl benzene-1,2,4-tricarboxylate

EC Number:

941-303-6

Cas Number:

1689576-55-3

Molecular formula:

not applicable, UVCB substance

IUPAC Name:

1,2,4-trinonyl benzene-1,2,4-tricarboxylate

Test material form:

liquid

Details on test material:

- Other: The constituent is an UVCB substance that, for the scope of (Q)SAR estimations, starting from the original composition was characterized by a PCA (Principal Component Analysis) in 15 representative components as follows:

SMILES
-----------
names

O=C(C1=C(C(OCCCCCCCCC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCCCCCCCCC
trinonyl benzene-1,2,4-tricarboxylate

O=C(OCCCCCCCCC)C1C=C(C(=O)OCCCCCCCCC)C=CC=1C(=O)OCC(C)CCCCCC
1-(2-methyloctyl) 2,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1=C(C(OCCCCCCCCC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCC(C)CCCCCC
2-(2-methyloctyl) 1,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(OCCCCCCCCC)C1=C(C=CC(=C1)C(=O)OCC(CCCCCC)C)C(=O)OCCCCCCCCC
4-(2-methyloctyl) 1,2-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1=C(C(OCC(CCCCC)CC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCCCCCCCCC
1-(2-ethylheptyl) 2,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(OCC(CCCCC)CC)C1C=C(C(=O)OCCCCCCCCC)C=CC=1C(=O)OCCCCCCCCC
2-(2-ethyheptyl) 1,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1C=C(C(OCC(CC)CCCCC)=O)C=CC=1C(OCCCCCCCCC)=O)OCCCCCCCCC
4-(2-ethyheptyl) 1,2-dinonyl benzene-1,2,4-tricarboxylate

O=C(OCCCCCCCCC)C1C=C(C(=O)OCCCCCCCCC)C=CC=1C(=O)OCC(CCC)CCCC
1-(2-propylhexyl) 2,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1=C(C(OCCCCCCCCC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCC(CCC)CCCC
2-(2-propylhexyl) 1,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(OCCCCCCCCC)C1=C(C(=O)OCCCCCCCCC)C=CC(C(=O)OCC(CCCC)CCC)=C1
4-(2-propylhexyl) 1,2-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1=C(C(OCCCCCCCCC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCCCCCCCCCCC
2-undecyl 1,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1=C(C(OCC(CCCC)CCC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCC(C)CCCCCC
1-(2-propylhexyl) 2-(2-methyloctyl) 4-nonyl benzene-1,2,4-tricarboxylate

O=C(C1=C(C(OCCCCCCCC)=O)C=CC(C(OCCCCCCCCC)=O)=C1)OCCCCCCCCC
1-octyl 2,4-dinonyl benzene-1,2,4-tricarboxylate

O=C(C1C=C(C(OCC(C)CCCCCC)=O)C=CC=1C(OCCCCCCCCCC)=O)OCCCCCCCCC
1-decyl 2-nonyl 4-(2-methyloctyl) benzene-1,2,4-tricarboxylate

O=C(C1C=C(C(OCC(C)CCCCCC)=O)C=CC=1C(OCC(C)CCCCCC)=O)OCC(C)CCCCCC
tris(2-methyloctyl) benzene-1,2,4-tricarboxylate

Results and discussion

Percutaneous absorption

Time point:

2 h

Dose:

Deposition dose: 4694 mg (instantaneous)

Parameter:

rate

Absorption:

<= 0 mg cm-2 h-1

Any other information on results incl. tables

DATA INPUT

As seen in the test materia definition, ‘Esterification products of 1,3-dioxo-2-benzofuran-5-carboxylic acid with nonan-1-ol’ is an UVCB substance that can be characterized in significant and reliable way, after a PCA (Principal Component Analisys) statistical procedure, by 15 principal components.

As key values for the dermal absorption of the above substance, we can select the endpoints related to trinonyl benzene-1,2,4-tricarboxylate, quantitatively the main component of the UVCB, which values are within the estimated range of the 15 principal components.

Substance

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

CAS number: 35415-27-1

Molecular weight: 588.86

Temperature: 20 deg C

Vapour Pressure (extrap. from exp.): 3.4E-08 Pa

Water solubility (calc.): 5.89E-7 mg/L

Log Kow (exp., skin, pH= 5.5): 10.8

Density (exp.): 978 mg/cm3

Melting Point (exp.): -53 deg C

Scenario parameters

Instantaneous deposition

- Istantaneous deposition dose(1): 4694 mg

- Affected skin area(2): 1000 cm2

- Maximum skin adherence(3): 7 mg/ cm2

- Thickness of stagnant air(4): 1 cm

- Weight fraction(5): 1

Timing parameters

- Start deposition: 0 hr

- End time observation: 2 hr

Report parameters

- Calculation intervals/hours: 7200

- Report intervals/hours: 60

(1) The instantaneous dose may occur by a splash or direct contact. The maximum amount of substance remaining on the skin is limited to 25 times the affected skin area (cm2). In case of instantaneous exposure, the duration of deposition and the dermal deposition rate are not considered in the calculation.

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; the expected more liquid will be excess and wash/fall off.

(2) Estimated skin surface of two hands of an adult. The assumed maximum full body surface of an adult, is 2000 cm2. The minimum is set to 0.1 cm2, the fingertip in contact with liquid or solid.

(3) In case of liquids any value between 0 and 7 mg/cm2, and in case of solids any value between 0 and 3 mg/cm2 is allowed. This value means that the mass of the substance on the skin surface will not exceed the input value. If deposition results in an increased mass on the skin above the input vale, it is assumed that the surplus gets lost from the skin.

(4) Average thickness of air layer around the body accounting for diffusive resistance of substance in air through work clothing. Apply 3 cm. in case of light clothes and 1 cm in case of nude skin.

(5) The fraction of the substance within the mixture based on weight. It means the weight of the substance divided by the weight of the solution it is in. An example may be 0.8 for a highly concentrated solution.

RESULTS

Deposition: Instantaneous

Tot. Deposition: 4694 mg

End time observation: 2 hr

 

Fraction absorbed: 0.0%

Amount absorbed: 0.0 mg

Lag time stratum corneum: 32.5 min.

 

Max. derm. abs.: 1.15E-08 mg/cm²/hr

Max. derm. abs. for 2000 cm²in 1 hour (from liquid): 0.00 mg

Dermal/Respiratory uptake ratio (from airborne vapour): R= 0.803

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)= 100/1.803=55.5%

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 ‘Esterification products of 1,3-dioxo-2-benzofuran-5-carboxylic acid with nonan-1-ol’ leads to the following results, obtained using the SkinPerm v2.04 model according to the input data:

Fraction absorbed: 0.0%
Amount absorbed: 0.0 mg
Lag time stratum corneum: 32.5 min.

Max. derm. abs.: 1.15E-08 mg/cm2/hr
Max. derm. abs. for 2000 cm2 in 1 hour (from liquid): 0.00 mg

Dermal/Respiratory uptake ratio (from airborne vapour): R= 0.803

Executive summary:

In-silico evaluation of dermal absorption shows that after 2 hours only practically no amount of deposited substance are absorbed within viable epidermis and therefore could enter in systemic circulation.