Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1991-10-28 to 1991-11-01
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable well-documented study report which meets basic scientific principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guideline
Qualifier:
no guideline required
Principles of method if other than guideline:
This study was conducted according to the EPA Good Laboratory Practice Standards outlined in 40 CFR Part 792, Federal Register Vol. 54, p. 158, 8/17/89 and according to EHSL SOP B.11.1.1. Method was used to assess dermal absorption

GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): SHF-61
- Specific activity (if radiolabelling): 92.5 nCi/mg
- Storage condition of test material: in hood at room temperature
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Taconic Farms
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 150-250g
- Housing: individual
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum):ad libitum
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 70
- Humidity (%): 50
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12


Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
The topical dose was administered to the clipped dorsal surface of the animals followed by covering the dosed area with a non-occlusive protective cell. After 24 h of exposure, the cell was removed and the dosed area wiped with olive oil.
Doses:
40mg (8mg/cm2 skin surface). Coverage is comparable to dermal administration at 2g/kg body weight
No. of animals per group:
5 female rats
Control animals:
no
Details on study design:
Five rats were administered a single topical dose of 40mg of SHF-61 containing 3.7uCi of 3H-SHF-61 (specific activity of 92.5 nCi/mg).

The topical dose was administered to the clipped dorsal surface of the animals followed by covering the dosed area with a non-occlusive protective cell. After 24 h of exposure, the cell was removed and the dosed area wiped with olive oil.

Animals were placed in individual metabolism cages. Urine and feces were collected at 24, 48, 72, and 96 hours post-dose. At the 96 hour time point, the animals were sacrificed by exposure to 100% CO2. The following tissues/organs were removed and analyzed for radioactivity: blood, small and large intestines, liver, kidney, stomach, retroperitoneal fat, treated (dose site) and untreated skin. The residual carcass was lyophilized prior to homogenization and measurement of 3H-activity. Radioactivity in the urine, urine wash and cage wash was counted. Fecal and most tissue samples were homogenized, oxidized and counted for radioactivity.

Results and discussion

Absorption in different matrices:

- Skin test site: 2.9%
- Skin, untreated site: 0.759%
- Blood: 0.14%
- Fat:0.158%
- Kidney: 0.02%
- Liver: 0.458%
- Small Intestine: 0.262%
- Large intestine 0.264%
- Stomach: 0.66%
- Carcass: 2.9%
- Urine: 2.0%
- Cage wash + cage wipe:
- Faeces: 7.8%
- Serial non-detects in excreta at termination:
- Receptor fluid, receptor chamber, donor chamber (in vitro test system):
Percutaneous absorptionopen allclose all
Dose:
40mg
Parameter:
percentage
Absorption:
ca. 2.9 %
Remarks on result:
other: 24h
Remarks:
treated skin
Dose:
40mg
Parameter:
percentage
Absorption:
ca. 4.9 %
Remarks on result:
other: 24h
Remarks:
tissues
Dose:
40
Parameter:
percentage
Absorption:
9.8 %
Remarks on result:
other: 24
Remarks:
excreted (7.8% in the feces, 2.0% in urine)

Applicant's summary and conclusion

Executive summary:

Five female Sprague Dawley rats were administered a single topical dose of 40mg SHF-61 (8mg/cm2 skin surface) fortified with 3H-labeled SHF-61 to determine the percutaneous absorption. The topical dose was administered to the clipped dorsal surface of the animals and covered with a non-occlusive protective cell.  After 24 h of exposure, the cell was removed and the dosed area wiped with olive oil.  Urine and feces were collected at 24, 48, 72, and 96 hours post-dose.  At the 96 hour time point, the animals were sacrificed and the amount of absorbed SHF-61 and its metabolites in the body was determined.  Nearly 18% (0.06 mg/cm2/hr) of the applied dose was absorbed in the rats with 2.9, 4.9% and 9.8% of the applied activity present in the treated skin, tissues and excreta, respectively.  The latter consists of 7.8% in the feces and 2.0% in the urine.  Low levels of activity were found in the liver (0.5%), untreated skin (0.8%) and remaining tissues (0.8%).

Detailed substance identity details supporting the use of 1-decene homopolymer, hydrogenated (CAS No. 68037-01-4) as read-across can be found in ‘Section 13-Assessment Reports’ of the IUCLID dossier.