Registration Dossier

Toxicological information

Dermal absorption

Currently viewing:

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Mass balance not complete, no cage wash reported, non-GLP

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
This study examined radiolabel excretion patterns after intravenous (iv) and topical administration of 14C-radiolabeled test substance in weanling Yoryshire sows. Radiolabel recovery from excrement collected over 6 days following iv does was calculated. Percutaneous absorption was determined from total urine and fecal excretion of radiolabel after topical application, corrected for incomplete excretion following iv administration.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
substance radiolabelled as [7-14C] benzoic acidPurity: the radiochemical purity >97%
Radiolabelling:
yes

Test animals

Species:
pig
Strain:
other: Yorkshire swine
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS- Age at study initiation: weanling- Weight at study initiation: approximately 20 kg each- Housing: a stainless steel metabolism cage- Individual metabolism cages: yes- Diet (e.g. ad libitum): 15% pig and sow pellets- Water (e.g. ad libitum): ad libitum- Acclimation period: at least 1 weekENVIRONMENTAL CONDITIONS- Temperature (°F): at standard temperature 72 °F- Photoperiod (hrs dark / hrs light): light-dark cycle (12 : 12 hr)No additional data

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Topical: ethanol, Intravenous: physiological saline
Duration of exposure:
6 days
Doses:
- Nominal doses: 40 μg/cm2- Dose volume: 200 μLNo additional data
No. of animals per group:
intravenous iv study: 4 pigsintravenous iv and topical administration study: 4 pigs
Control animals:
no
Details on study design:
DOSE PREPARATION- Method for preparation of dose suspensions: Dosing solutions were prepared for iv injection by addition of cold compound in ethanol solution to the radiolabeled material. This was further diluted in sterile physiological (pH 7.4) saline to a final concentration of 0.02 mg/mL and a radioactive concentration of 1 μCi/mL. For topical administration, dosing solutions were prepared by diluting cold and radiolabeled compound in 100% ethanol, to a final concentration of 1 mg/mL and 50 μCi/mL.- Method of storage: Both topical and iv dosing solutions were prepared within approximately 1 week of use and were stored refrigerated until needed.VEHICLE- Amount(s) applied (volume or weight with unit): 200 μLTEST SITE- Preparation of test site: abdominal area- Area of exposure: 5 × 1 cm- Type of cover / wrap if used: A nylon screen and a nonocclusive gauze pad were used to cover the foam border and were held in place by wrapping the pig's midsection with tape.SAMPLE COLLECTION- Collection of urine and faeces: Total urine and feces could be collected separately (at room temperature. Urine was collected at 6, 12 (where available), and 24 hr and daily thereafter for a total of 6 days. Feces were collected daily for 6 days.- Analysis of organs: At the end of the study, pigs were euthanized with 60-80 mg/kg (iv) pentobarbital solution. Liver, both kidneys, and spleen were removed and weighed. Skin at the application site was excised.- Pad and faom border were assessed for radioactivitySAMPLE PREPARATION- Storage procedure: Urine: The volume of each collection was measured and an aliquot was stored in a polypropylenevial at -20℃ until analysis. Feces: The total sample, placed in plastic bags, was stored at -20℃. Organs: Small samples of each organ, along with samples of lung, colon, skeletal muscle, and skin were stored as described above.ANALYSIS- Method type(s) for identification (e.g. GC-FID, GC-MS, HPLC-DAD, HPLC-MS-MS, HPLC-UV, Liquid scintillation counting, NMR, TLC) The trapped radiolabel was measured using Liquid scintillation counting.No additional data

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
- Urine: 23.7% ± 2.7%No additional data
Total recovery:
Radiolabel recovery (% dose) following iv administration of 14C-labeled compounds to pigsUrine: 84.5±9.0, Feces: 4.6±1.2, Carcass: 0.1±0.05, Total recovery: 89.3±9.3Radiolabel recovery (% dose) following topical administration of 14C-labeled compounds to pigsUrine: 20.0±2.3, Feces: 2.9±0.3, Carcass: 0.8±0.4, Boder: 40.2±0.3, Dosed skin: 12.2±1.0, Adjacent skin: 9.1±2.1, Total recovery: 85.4±4.2
Percutaneous absorptionopen allclose all
Dose:
40 μg/cm2
Parameter:
percentage
Absorption:
>= 23.3 - <= 28.1 %
Remarks on result:
other: 72 h
Remarks:
Corrected absorption (% dose) of total excrement
Dose:
40 μg/cm2
Parameter:
percentage
Absorption:
>= 21 - <= 26.4 %
Remarks on result:
other: 72 h
Remarks:
Corrected absorption (% dose) of urine alone
Conversion factor human vs. animal skin:
No information provided

Applicant's summary and conclusion

Conclusions:
The test substance was primarily excreted into urine > 80%. Corrected absorption (% dose) of total excrement was 25.7%.
Executive summary:

This study examined radiolabel excretion patterns after intravenous (iv) and topical administration of 14C-radiolabeled test substance in weanling Yoryshire sows. Radiolabel recovery from excrement collected over 6 days following iv does was calculated. Percutaneous absorption was determined from total urine and fecal excretion of radiolabel after topical application, corrected for incomplete excretion following iv administration.

The test substance was primarily excreted into urine > 80%. Corrected absorption (% dose) of total excrement was 25.7%.