Registration Dossier

Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
supporting study
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:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

GLP compliance:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
methyl (2E)-3-methoxy-2-[2-({[6-(trifluoromethyl)pyridin-2-yl]oxy}methyl)phenyl]acrylate
EC Number:
601-478-9
Cas Number:
117428-22-5
Molecular formula:
C18H16F3NO4
IUPAC Name:
methyl (2E)-3-methoxy-2-[2-({[6-(trifluoromethyl)pyridin-2-yl]oxy}methyl)phenyl]acrylate
Test material form:
solid
Details on test material:
- Purity: 93.3-99.8% (see individual test record for specific details)
Specific details on test material used for the study:
93.3% purity

Administration / exposure

Type of coverage:
other: In vitro
Remarks:
Human epidermis tissue
Vehicle:
acetone
Duration of exposure:
55 hours
Doses:
0.1 g/cm2 (undiluted solid) and 40 μg/cm2 (acetone solution)
Details on in vitro test system (if applicable):
The absorption of the test substance has been measured in vitro through human epidermis. The material was applied undiluted and as a 1600 μg/mL solution in acetone. The undiluted material was applied as a dry powder to epidermal membranes as an infinite at a rate of 0.1 g/cm2 and occluded for the duration of the exposure period (55 hours), while the solution in acetone was applied at 25 μL/cm2 (40 μg/cm2) and left unoccluded throughout the entire exposure period allowing the acetone vehicle to evaporate and the test substance to remain as a dried-on deposit.

Results and discussion

Absorption in different matrices:
No absorption of the solid test substance was detected from the undiluted technical grade material (<0.017 μg/cm2/h) until 8 hours after application. After this time absorption maintained an unchanging rate (0.020 μg/cm2/h) until the end of the exposure period (55 hours).
From the 40 μg/cm2 dried-on deposit from the 1600 μg/ml solution in acetone, test substance absorption after the first hour of exposure maintained a constant rate of 0.076 μg/cm2/h.

Applicant's summary and conclusion

Conclusions:
When applied as a dry powder and in excess, absorption of the test substance through human epidermis is very slow from unformulated technical grade material, when compared with the absorption rates of other penetrants measured using this in vitro technique. Following evaporation of the acetone vehicle, absorption from the dried-on deposit also indicates a very slow rate of human skin penetration for the test substance.
Executive summary:

The absorption of the test substance has been measured in vitro through human epidermis. The material was applied undiluted and as a 1600 μg/mL solution in acetone. The undiluted material was applied as a dry powder to epidermal membranes as an infinite at a rate of 0.1 g/cm2 and occluded for the duration of the exposure period (55 hours), while the solution in acetone was applied at 25 μL/cm2 (40 μg/cm2) and left unoccluded throughout the entire exposure period allowing the acetone vehicle to evaporate and the test substance to remain as a dried-on deposit.

No absorption of the solid test substance was detected from the undiluted technical grade material (<0.017 μg/cm2/h) until 8 hours after application. After this time absorption maintained an unchanging rate (0.020 μg/cm2/h) until the end of the exposure period (55 hours). From the 40 μg/cm2 dried-on deposit from the 1600 μg/mL solution in acetone, test substance absorption after the first hour of exposure maintained a constant rate of 0.076 μg/cm2/h.

When applied as a dry powder and in excess, absorption of the test substance through human epidermis is very slow from unformulated technical grade material, when compared with the absorption rates of other penetrants measured using this in vitro technique. Following evaporation of the acetone vehicle, absorption from the dried-on deposit also indicates a very slow rate of human skin penetration for the test substance.