Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented study reported in peer-reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Dermal toxicity elicited by phthalates: Evaluation of skin absorption, immunohistology, and functional proteomics
Author:
Pan T-L, Wang P-W, Aljuffali IA, Hung Y-Y, Lin C-F and Fang J-Y
Year:
2014
Bibliographic source:
Food Chem Toxicol 65: 105-114, 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. This was mounted between the donor and receptor compartments of Franz cells with the stratum corneum facing upwards into donor side. The receptor medium contained 40% ethanol in pH 7.4 buffer. The donor medium was 5.4 mM test substance in 40% ethanol/pH 7.4 buffer. The diffusion area between compartments was 0.785 cm2. The temperature of receptor medium was maintained at 37°C. Aliquots were taken from the receptor medium at determined intervals and immediately replaced with an equal volume of medium. The skin was removed from the cells after a 12 hour permeation, washed and weighed, cut with scissors, and homogenized in methanol. The supernatant collected following centrifugation was assayed 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
Details on test material:
- Name of test material (as cited in study report): Trioctyl trimellitate (TOTM)
- Analytical purity: > 99%
Radiolabelling:
no

Test animals

Species:
other: Nude mouse and pig
Strain:
other: Mouse - ICR-Foxn1nu; pig - not specified
Sex:
female
Details on test animals or test system and environmental conditions:
MICE
TEST ANIMALS
- Source: National Laboratory Animal Centre, Taipei, Taiwan.
- Age on supply: 8 weeks
- Diet: Laboratory diet, ad libitum
- Water: ad libitum

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


PIGS
TEST ANIMALS
- Source: Animal Technology Institute, Miaoli, Taiwan.
- Age on supply: 1 week
- 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: 40% ethanol/pH 7.4 buffer
Duration of exposure:
12 hours
Doses:
N/A
No. of animals per group:
4
Control animals:
no
Details on study design:
N/A
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 deg C
- Humidity: Not reported
- Occlusion: No

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 nmol/mg; pig - 0.35 nmol/mg
Percutaneous absorption
Dose:
5.4 mM
Parameter:
percentage
Absorption:
0 %
Remarks on result:
other: 12 hours
Remarks:
Flux (nmol/cm2/hour) = 0 for both mouse and pig skin

Applicant's summary and conclusion

Conclusions:
In-vitro examination of dermal absorption indicates that the substance does not significantly penetrate the skin
Executive summary:

Full-thickness skin from the dorsal region of mice and pigs has been used to examine skin absorption in-vitro. A number of phthalate esters were examined in addition to the registered substance, TOTM. Both dermal reservoir and transdermal flux were examined. Substance remaining in the skin reservoir was indicative of skin deposition, whereas the substance in the receptor medium implies in-vivo availability into systemic absorption. No significant skin accumulation of TOTM was noted. No TOTM was found in the receptor medium after treatment for 12 hours.