Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study report presented sufficient experimental detail, however, it was not conducted according to a testing guideline or under the GLP regulations.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Principles of method if other than guideline:
Standard Franz difussion cell methodology with radio-labeled 2,3-epoxypropyl neodecanoate isomer was used.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: Liquid at room temperature.
Details on test material:
The pure 14C labeled test substance was 2,3-epoxypropyl-3-carboxy-3,6-dimethyl heptanoate, the predominate isomer of 2,3-epoxypropyl neodecanoate.
Radiolabelling:
yes
Remarks:
14C-2,3-epoxypropyl neodecanoate isomer

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals and environmental conditions:
Male C3H mice also served as a source of skin. Fisher 344 rats (approximately 250 gm) and male C3H mice (approximately 25 gm) were obtained from the Central Laboratories for the Blood Banks (CLB), Amsterdam, The Netherlands. Animals were kept on a 12 h light/dark cycle in humidity (60±15% relative humidity) and temperature (22±2°C) controlled mass-air-displacement rooms and following an acclimation period of 1 week were used as the source for skin. A standard rodent diet and deionized water were supplied ad libitum. Fresh full thickness healthy human breast skin was obtained from patients undergoing mammoplastic reduction surgery in a regional hospital, MCA, Alkmaar, The Netherlands.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
DMSO
Duration of exposure:
At least 24 hr.
Doses:
Five uL neat
No. of animals per group:
Study was in vitro.
Control animals:
no
Details on study design:
Study was conducted in vitro, see below.

Results and discussion

Signs and symptoms of toxicity:
not specified
Remarks:
test system was in vitro.
Dermal irritation:
not specified
Remarks:
test system was in vitro.
Absorption in different matrices:
The amount of absorption in the in vitro difussion system was enhanced by the additon of 2.5 BSA to the receptor fluid.
Total recovery:
No data
Percutaneous absorption
Dose:
5 uL neat test substance isomer.
Parameter:
percentage
Absorption:
ca. 0.2 %
Remarks on result:
other: 24 hr
Remarks:
for human skin samples.
Conversion factor human vs. animal skin:
No data

Applicant's summary and conclusion

Conclusions:
The data demonstrated that the 2,3-epoxypropyl neodecanoate isomer was metabolized in vitro in skin samples from rat, mouse and humans to the corresponding diol and ester hydrolysis product. Rat skin was most permeable to the test substance isomer. Human skin samples were approximately an-order-of-magnitude less permeable than rodent skin.
Executive summary:

The dermal penetration and metabolism of radio-labeled 2,3 -epoxypropyl neodecanoate isomer was assessed in vitro using diffison cell technology with skin samples from rats, mice and humans. The data demonstrated that the 2,3-epoxypropyl neodecanoate isomer was metabolized in vitro in skin samples from rat, mouse and humans to the corresponding diol and ester hydrolysis product. Rat skin was most permeable to the test substance isomer. Human skin samples were approximately an-order-of-magnitude less permeable to the 2,3 -epoxypropyl neodecanoate isomer than rodent skin.