Naphthenic acids, zinc salts

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Penetration of 65Zn through the skin of rats

Author:

Hallmans G & Liden S

Year:

1979

Bibliographic source:

Acta. Derm. Venereol. 59(2):105-112

Materials and methods

Principles of method if other than guideline:

The penetration of zinc through rat skin was studied radiochemically and radioautographically following application through suspension and tape containing radioactive zinc.

GLP compliance:

no

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): 65Zn-Zinc oxide suspension or 65-Zn labelled Zinc tape

Radiolabelling:

yes

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 85-180 g
- Housing: Individually in metabolism cages of acrylic resin and stainless steel
- Individual metabolism cages: yes
- Diet (e.g. ad libitum): Standard laboratory diet containing 100 µg Zinc/g, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

not specified

Duration of exposure:

2 h

Doses:

Zinc oxide, 125 µg Zn/mL

No. of animals per group:

Six

Details on study design:

DOSE PREPARATION
- 65Zn-Zinc oxide was used in a suspension (125 µg Zn and 0.7 mCi 65Zn/mL, pH 8, NEN Chemicals GmbH, Dreieich, West Germany) and in a Zinc tape.
- 65Zn-labelled Zinc tape was prepared by irradiating Zinc oxide powder in a quartz glass tube with thermal neutrons at a flux of approximately 2.2 X E-13 neutrons.cm-2.sec-1 for 72 h (AB Atomenergi, Studsvik, Sweden). The specific activity was 11.8 nCi 65Zn/µg Zn. The irradiated Zinc oxide was mixed mechanically for 3 h with an adhesive substance composed of gum, resin and trichloroethylene to give a final concentration of Zinc of 17% of the total dry weight. This mixture was then spread as evenly as possible on cotton gauze and dried. The range of 65Zn activity was 5-10 µCi/cm2.
- Tape was stored for one month before use in order to practically eliminate activity of other Zinc radioisotopes


APPLICATION OF DOSE:
- Suspension: 25 µL applied topically to 3 cm2 of shaved area on both side of the animal
- Tape: 5 cm2 piece of the Zinc-tape was applied and covered with a plastic film and a bandage of plastic coated tape


SAMPLE COLLECTION
- Collection of blood: Collected from tail vein
- Analysis of organs: Small tissue samples of liver, GIT, heart, testis & carcass were analysed for 65Zn activity by gamma scintillation
- Analysis of skin: Treated skin areas were analysed


ANALYSIS
- Method type(s) for identification: Gamma scintillation counter


HISTOLOGY
- Blocks of the skin were either frozen and sections were taken by cryostat or routinely processed & embedded in paraffin; 6 µm sections were taken and stained with haematoxylin

Details on in vitro test system (if applicable):

Not applicable

Results and discussion

Signs and symptoms of toxicity:

not examined

Dermal irritation:

not examined

Absorption in different matrices:

Absorption (%) from the skin: 1.9 ± 0.2
- % absorbed by carcass: 52.0 ± 4.2
- % absorbed by liver: 22.8 ± 1.6
- % absorbed by GIT: 25.2 ± 4.0

Absorption in blood: 65Zn rapidly appeared in the blood and other tissues. The maximum 65Zn activity in serum occurred within or around the first hour after the application of the test material.

Relative activity
- Serum: 1.2 ± 0.1
- Coagulation: 0.5 ± 0.1
- Liver: 8.0 ± 1.0
- Heart: 1.3 ± 0.2
- Testis: 0.3 ± 0.0

Autoradiography: 65Zn activity was seen in both dermis and panniculus carnosus. The activity was most concentrated on and near the epidermis and around hair follicles in dermis.

Total recovery:

No data

Percutaneous absorption

Dose:

125 µg Zn/mL, pH 8

Parameter:

percentage

Absorption:

1.9 %

Remarks on result:

other: 2 h

Remarks:

% absorbed activity

Conversion factor human vs. animal skin:

No data

Any other information on results incl. tables

Additional study: In the same study, percutaneous absorption of the 65Zinc in rat skin was observed to be 4.1 ± 0.6 & 1.6 ± 0.3% at pH 1 & 4, respectively on topical application of the radioactive zinc chloride in acidic solution (pH = 1). Less acidic solutions with ZnCl₂or with ZnO resulted in a dermal absorption of less than 2%. In this study only the absorption into the body, excluding the skin, was determined. No data were available as to the effect of zinc chloride solutions with pH = 1 on dermal integrity.

Applicant's summary and conclusion

Conclusions:

Under the test conditions, percutaneous absorption of the Zinc in rat skin was observed to be 1.9 ± 0.2% on topical application of the radioactive test material.

Executive summary:

A study was conducted to determine the penetration of 65Zn from Zinc oxide suspension and from a Zinc tape containing Zinc oxide through the intact skin of rats.

 

65Zn rapidly appeared in the blood and other tissues. The maximum 65Zn activity in serum occurred within or around the first hour after the application of the test material. Absorption through skin was estimated to be 1.9 ± 0.2% of which 52 ± 4.2, 22.8 ± 1.6 & 25.2 ± 4.0% was absorbed in carcass, liver & GIT, respectively. Autoradiographically, 65Zn activity was seen in both dermis and panniculus carnosus. The activity was most concentrated on and near the epidermis and around hair follicles in dermis. However it must be noted that in this study other zinc compounds were tested and no distinction was made between the different zinc compounds during the observations.

 

Under the test conditions, percutaneous absorption of the Zinc in rat skin was observed to be 1.9 ± 0.2% on topical application of the radioactive test material.