Registration Dossier

Administrative data

Endpoint:
dermal absorption in 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:
publication
Title:
In vivo percutaneous absorption of fragrance ingredients in rhesus monkeys and humans
Author:
Bronaugh RL, Wester RC, Bucks D, Maibach HI & Sarason R
Year:
1990
Bibliographic source:
Food Chem Toxicol 28, 369-373

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Benzophenone
- Substance type: aryl ketone
- Radiochemical purity (if radiolabelling): 99.9%
- Specific activity (if radiolabelling): 5.4 mCi/mmoL
- Other: Supplier: Pathfinder Laboratories, St. Louis, MO, USA)
Radiolabelling:
yes

Test animals

Species:
monkey
Strain:
other: rhesus
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: California Primate Centre
- Age at study initiation: 10, 14, 19 and 19 years
- Individual metabolism cages: yes

Administration / exposure

Type of coverage:
other: The application sites were occluded by one of two different methods. In some experiments, a plastic wrap was held in place over the application site with adhesive tape.In other experiments, a glass chamber was glued to the skin around the application site
Vehicle:
acetone
Remarks:
10 - 20 µL/cm2
Duration of exposure:
24 hours
Doses:
- Nominal doses: 4 µg/cm2 to a lightly clipped skin area of 1 cm2
No. of animals per group:
A total of 4 animals was used
Control animals:
no
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: the radiolabelled test item was diluted with acetone
- Method of storage: no storage

VEHICLE
- Justification for use and choice of vehicle (if other than water): good solubility
- Amount(s) applied (volume or weight with unit): 10-20 µL/cm2 of skin

TEST SITE
- Preparation of test site: the test site was lightly clipped
- Area of exposure: 1 cm2
- % coverage: no data
- Type of cover / wrap if used: plastic wrap or glass chamber

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: monkeys were restrained in metabolic chairs for 24 hours

REMOVAL OF TEST SUBSTANCE
- Removal of protecting device: after 5 days p.a.
- Washing procedures and type of cleansing agent: 24 hour p.a., the test sites were washed with soap and water. The wash solution was applied to a ryon-cotton ball atached to a pair of curved foreceps.
- Time after start of exposure: 24 hours

SAMPLE COLLECTION
- Collection of blood: not sampled
- Collection of urine and faeces: urine samples were collected in metabolic cages for anotherv4 days after the 24 hour exposure period
- Collection of expired air: not sampled
- Terminal procedure: none
- Analysis of organs: not performed

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting
- Liquid scintillation counting results (cpm) converted to dpm as follows: with a parenteral correction factor according to Feldmann and Maibach (1969)
- Validation of analytical procedure: no data
- Limits of detection and quantification: no data

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
- Skin wash: wash solutions were determined for radioactivity
- Urine: detemined for 4 days after 24 hours exposure
Percutaneous absorptionopen allclose all
Dose:
4 µg/cm2
Parameter:
percentage
Absorption:
ca. 43.8 %
Remarks on result:
other: Urine collection over 5 days; means and SD
Remarks:
Unoccluded site
Dose:
4 µg/cm2
Parameter:
percentage
Absorption:
ca. 68.7 %
Remarks on result:
other: Urine collection over 5 days; means and SD
Remarks:
Plastic wrap
Dose:
4 µg/cm2
Parameter:
percentage
Absorption:
ca. 68.6 %
Remarks on result:
other: Urine collection over 5 days; means and SD
Remarks:
Glass chamber
Conversion factor human vs. animal skin:
Percutaneous absorption in humans was determinded by measuring the radioactivity excreted in the urine samples collected each day, using liquid scintillation counting and then correcting the amount of radioactivity for complete excretion with a parenteral correction factor. Topical values were divided by this percentage to give total percutaneous absorption.
The means of these values were 92.6% for benzophenone in monkeys.

Any other information on results incl. tables

Table 1: Percutaneous absorption of Benzophenone in the monkeys

Absorption (% of the applied dose)

 

Site occluded with

Compound

Unoccluded site

Plastic wrap

Glass chamber

Benzophenone

43.8 ± 7.5

68.7 ± 6.4

68.6 ± 4.6

 

Applicant's summary and conclusion

Conclusions:
The percentage of dermal absorption for Benzophenone in rhesus monkeys was about 70% after occlusive conditons. The authors concluded that the skin of rhesus monkeys resembles well the human skin with regard to percutaneous absorption of fragrance ingredients.
Executive summary:

The percutaneous absorption of benzophenone and other fragrances was determined in vivo in monkeys. Absorption through occluded skin was high (about 70% of the applied dose within 24 hours). Under unoccluded conditions skin penetration was reduced, presumably because of evaporation.