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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
2014
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2014

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Full-thickness skin on dorsal region was excised from mice or pigs after sacrifice.
The skin was mounted between donor and receptor of Franz cell with stratum corneum (SC) facing upwards into donor side. The receptor medium (5.5 ml) contained 40% ethanol in pH 7.4 buffer for maintaining sink condition. The donor medium was 5.4 mM phthalates in 40% ethanol/pH 7.4 buffer. The diffusion area
between compartments was 0.785 cm2. The stirring rate of the stirrers in receptor was 600 rpm. The temperature of receptor was maintained at 37 C. A 300-ll aliquot was taken from receptor at determined intervals and immediately replaced with an equal volume of medium. The sample number in this experiment was four. The skin was removed from the cell after a 12-h permeation. The skin was washed and weighed, cut with scissors, and positioned into a glass homogenizer containing methanol. The duration for homogenization was 5 min. Then the resulting mixture was centrifuged at 10,000 rpm for 10 min. The supernatant was collected for quantifying phthalate content by high-performance liquid chromatography (HPLC).
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
EC Number:
222-020-0
EC Name:
Tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
Cas Number:
3319-31-1
Molecular formula:
C33H54O6
IUPAC Name:
tris(2-ethylhexyl) benzene-1,2,4-tricarboxylate
Constituent 2
Reference substance name:
Tri-(2-ethylhexyl)trimellitate
IUPAC Name:
Tri-(2-ethylhexyl)trimellitate
Details on test material:
- Name of test material (as cited in study report): Tri-(2-ethylhexyl)trimellitate
- Molecular formula (if other than submission substance): C33-H54-O6
- Molecular weight (if other than submission substance): 546.79
- Smiles notation (if other than submission substance): CCCCC(CC)COC(=O)c1ccc(c(c1)C(=O)OCC(CC)CCCC)C(=O)OCC(CC)CCCC
- InChl (if other than submission substance): 1S/C33H54O6/c1-7-13-16-25(10-4)22-37-31(34)28-19-20-29(32(35)38-23-26(11-5)17-14-8-2)30(21-28)33(36)39-24-27(12-6)18-15-9-3/h19-21,25-27H,7-18,22-24H2,1-6H3

- Analytical purity: >99%
Radiolabelling:
no

Test animals

Species:
other: nude mice and pigs
Strain:
other: mice: ICE-Foxn1nu; pig: not specified
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
MICE
- Source: National Laboratory Animal Centre, Taipei, Taiwan.
- Age on supply: 8 weeks

PIGS
- Source: Animal Technology Institute, Miaoli, Taiwan.
- Age on supply: 1 week

BOTH SPECIES
- Diet: Laboratory diet, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 - 26 deg C
- Humidity (%): 55 - 65 %

Administration / exposure

Type of coverage:
open
Vehicle:
other: Receptor fluid: 40% ethanol in pH 7.4 buffer
Duration of exposure:
12 hours
Doses:
donor medium contained 5.4 mM TOTM
No. of animals per group:
4
Control animals:
no
Details on in vitro test system (if applicable):
SKIN PREPARATION
- Source of skin: Untreated nude mice and untreated pigs
- Type of skin: Intact full thickness dorsal skin

PRINCIPLES OF ASSAY
- Diffusion cell: Franz cell
- Receptor fluid: 40% ethanol in pH 7.4 buffer
- Solubility od test substance in receptor fluid: Not reported
- Static system: Yes
- Test temperature: 37 °C
- Humidity: Not reported
- Occlusion: No (but substance not volatile)

Results and discussion

Absorption in different matrices:
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): Mouse - 0; pig - 0
- Skin preparation (in vitro test system): Mouse - 1.32 +/- 0.53 nmol/mg; pig - 0.35 +/- 0.19 nmol/mg
Percutaneous absorption
Dose:
5.4 mM
Parameter:
percentage
Absorption:
0 %
Remarks on result:
other: 12
Remarks:
for both mice and pigs, flux [nmol/square cm/hour] was 0

Applicant's summary and conclusion

Conclusions:
In vitro skin absorption examination of triethylhexyl trimellitate (TOTM) via analytical methods in Franz cells using full-thickness skin from female nude mice and pigs revealed, that TOTM does not significantly penetrate the skin.
Executive summary:

The in vitro skin absorption of triethylhexyl trimellitate was determined via analytical methods in Franz cells using full-thickness skin samples excised from female nude mice and specific pathogen-free pigs. The receptor medium contained 40% ethanol, and the donor medium was 5.4 mM triethylhexyl trimellitate in 40% ethanol/pH 7.4 buffer. The skin samples were removed from the cells after a 12 h exposure and tape-stripped. The accumulation of triethylhexyl trimellitate was 1.32 ± 0.53 nmol/mg in nude mouse and 0.35 ± 0.19 nmol/mg in pig skin; the flux was 0 nmol/cm2/h for both mouse and pig skin. Triethylhexyl trimellitate was not found in the receptor medium after 12 h, indicating no biologically relevant availability for dermal absorption.

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