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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:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: non-GLP but with QA-statement.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: The SCCP's notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (reference: SCCNFP/0321/00 Final).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Gold fragrance material: AHTN (6-acetyl-1 ,1 ,2,4,4,7-hexamethyltetraline),
Radiolabelling:
yes
Remarks:
Radiolabelled 14C-AHTN (uniformly labelled in the aromatic ring – radiochemical purity 99.6%)

Test animals

Species:
human
Strain:
other: Full-thickness human female breast skin and abdominal skin.
Sex:
female
Details on test animals and environmental conditions:
Full-thickness human female breast skin and abdominal skin.

Administration / exposure

Type of coverage:
open
Vehicle:
ethanol
Duration of exposure:
24 hours
Doses:
AHTN was prepared as a 1% (w/v) solution in ethanol (96% v/v). Target dose: 20 µl/cm2
No. of animals per group:
N/A
Control animals:
no

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Total recovery:
Overall recovery was 92,5%
Percutaneous absorption
Dose:
200 ug AHTN/cm2
Parameter:
percentage
Absorption:
ca. 4.1 %
Remarks on result:
other: 24 hours
Remarks:
4.06% of the applied dose in 24 hours
Conversion factor human vs. animal skin:
N/A

Any other information on results incl. tables

Following 24 hours exposure, 0.760 ug test compound/cm2 (corresponding to 0.379% of the applied dose) had permeated through epidermal membranes. The majority of applied test compound (84.7% of the applied dose) was found in the 24 hour surface wipe and donor chamber wash plus wipe. The stratum corneum tape strips contained 3.80% of the applied dose and the epidermis, plus any remaining stratum corneum after tape strpping, 3.49% of the applied dose. The levels of test compound in the epidermis, plus any remaining stratum corneum after tape stripping, filter paper and receptor fluid were combined to produce a total absorbed dose value of 4.06% of the applied dose.

Applicant's summary and conclusion

Conclusions:
This in vitro dermal absorption study with 14C-ring labelled AHTN using human epidermal membranes indicated that 4.1% of the applied dose is absorbed over 24 hours.
Executive summary:

The dermal absorption (non-GLP, but with QA-statement) of AHTN was determined over a 24-hr period according to the methodology of the SCCNFP. Radiolabeled 14C-AHTN (uniformly labelled in the aromatic ring – radiochemical purity 99.6%) was applied in 1% (w/v) solution in ethanol (96% v/v) to human epidermal membranes (prepared from full thickness female breast or abdominal skin and assayed for integrity with tritiated water) supported on a piece of filter paper (for strength) in glass diffusion cells (n=12). There were two control cells. The area of the membrane available for absorption was approximately 1 cm2 and the applied dose was a mean of (n=12) 20±0.4 μL/cm2 (hence, 200 μg AHTN/cm2). Receptor fluid (6% Volpo N20 (to enhance solubility) in pH 7.4 phosphate buffered saline) was sampled at 1, 2, 6, 12 and 24 hrs. After 24 hrs the epidermal membranes were wiped and stripped. The amount of material absorbed into the receptor phase after 24 hr was 0.38±0.06% of the applied dose. The majority of applied AHTN (85±2% of the applied dose) was found in the 24-hr surface wipe and donor chamber wash plus wipe. The stratum corneum tape strips contained 3.8±0.3% of the applied dose and the remaining stratum corneum plus epidermis 3.5±0.3% of the applied dose. As per SCCNFP guidelines, levels of AHTN in the remaining stratum corneum plus epidermis, filter paper (on which the epidermis samples rested; 0.19±0.03% of the applied dose) and permeated AHTN were combined to produce a total absorbed dose value of 4.1±0.4% of the applied dose. The evaporative loss (assessed in a separate experiment under the same conditions) over 24 hrs was 2.9% of the applied dose. Overall-recovery of radioactivity at 24 hrs was 92.5±0.7%.