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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
in or before 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: acceptable, well-documented study which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Principles of method if other than guideline:
in vivo disposition after dermal administration
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): hydroxybenzoic acid, 4-hydroxybenzoic acid, p-hydroxybenzoic acid
- Radiochemical purity (if radiolabelling): C14-ring labelled
- Specific activity (if radiolabelling): 58.6 µCi/µmol
- Locations of the label (if radiolabelling): aromatic ring
- Producer: Moravek Biochemicals, Brea, CA, USA
- Radiochemical purity: > 98%
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC, USA
- Age at study initiation: 29 +-2days
- Weight at study initiation: 52-74 g
- Fasting period before study: 24 hours
- Housing: polycarbonate cages
- Individual metabolism cages: yes (individually 3 days before dosing)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 25 °C +-2°C
- Humidity (%): 50 +-10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: ethanol
Duration of exposure:
120 hours
Doses:
5 µg/animal, 3.9 µg/cm², approx. 2µCi
No. of animals per group:
3 or 4, no clear data
Control animals:
no
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: in Ethanol
- Method of storage:

APPLICATION OF DOSE:

VEHICLE
- Amount(s) applied (volume or weight with unit): test item applied in 10µL Ethanol
- Concentration of test item in vehicle: 5 µg/10µL

TEST SITE
- Preparation of test site: removel of hair with electric clipper, clipped skin was washed with acetone
- Area of exposure:1.27 cm2
- % coverage: 100
- Type of cover / wrap if used: 5 mL plastic cup glued (cyano acrylate adhesive) over treated skin

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes: latex tubing placed around the animals behind the forelegs using a wire

REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: yes
- Washing procedures and type of cleansing agent: 1 mL wash solution Ivory soap/water (1/1), cotton ball was used (forceps and rubbing) to absorb washing solution and test item, washing with soap: 2 times, followed by washing with water (1 mL, cotton ball): 2 times, followed by drying with cotton ball. Plastic cup replaced.
- Time after start of exposure: 24 h

SAMPLE COLLECTION
- Collection of urine and faeces: yes
- Collection of expired air: no
- Terminal procedure: after 120 h, animals were killed, plastic cup was removed, treated skin was cut away. Plastic cup, skin and whole animal were analyse for radioactivity.
- Analysis of organs: no

SAMPLE PREPARATION
- Preparation details: carcasses were frozen in liquid N2, homogenised, weighed, combusted (to absorb C14 labelled CO2) and analysed

CHEMICALS for Analysis:
- Flo-Scint II, Carbosorb and Permafluor V (all from Packard Instruments Co.

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
- urine was not analyzed with HPLC because of low counts.

Results and discussion

Signs and symptoms of toxicity:
no effects
Dermal irritation:
not specified
Absorption in different matrices:
- occlusive cover: yes
- Skin wash: after 24 hours
- Skin test site: dorsal skin
- Carcass: treated-slinsite
- Urine: yes
- Faeces: yes
Total recovery:
- Total recovery: 99.92%
- Wash: 95.9+-0.3%
- Body: 0.28+-0.01%
- Urine: 1.9+-0.3%
- Treated skin: 1.8+-0.2%
- Feces: 0.04+-0.19%
- Untreated skin: < 0.005%

Any other information on results incl. tables

The dermal absorption of radiolabelled 4 -HBA through the skin of 29-day-old female rats was examined over a period of 120 hours.

The dermal absorption was minimal, 4% of the dosage.

The recovery of the total radiolabelled dosage was 99.92%, 95.9% remained at the treated skin site.

Applicant's summary and conclusion

Conclusions:
Only a minimal amount of 4-HBA (4% of the dosage) was absorbed.
Executive summary:

The dermal absorption of radiolabelled 4 -HBA through the skin of 29-day-old female rats was examined over a period of 120 hours.

The dermal absorption was minimal, 4% of the dosage.

The recovery of the total radiolabelled dosage was 99.92%, 95.9% remained at the treated skin site.