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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across based on grouping of substances (category approach)
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-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Percutaneous uptake of zinc in rabbit skin
Author:
Kapur SP, Bhussry BR, Rao S & Harmuth-Hoene E
Year:
1974
Bibliographic source:
Proc. Soc. Exp. Biol. Med. 145(3):932-937

Materials and methods

Principles of method if other than guideline:
The percutaneous uptake of Zinc in rabbits was studied radiochemically and radioautographically using single- and double-dose applications of the test material.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc oxide
- Preparation: 65Zinc oxide was prepared by adding Sodium hydroxide to a solution of Zinc chloride (International Chemical and Nuclear Corporation, Irvine, CA) and drying the resulting precipitate at 125 °C
- Locations of the label (if radiolabelling): 65Zn
Radiolabelling:
yes

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Adult
- Weight at study initiation: 2 kg

Administration / exposure

Type of coverage:
open
Vehicle:
other: 1:1 mixture of glycerin and propylene glycol
Duration of exposure:
30 or 48 h
Doses:
- Dose: 2.5 mg Zinc compound containing 5 µCi 65Zn
No. of animals per group:
Treatment: Two
Control: One
Control animals:
yes
Remarks:
Treated with non-radioactive test material
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: 65Zinc oxide was prepared by adding Sodium hydroxide to a solution of Zinc chloride (International Chemical and Nuclear Corporation, Irvine, CA) and drying the resulting precipitate at 125 °C.


APPLICATION OF DOSE: Test material, specific activity of 131 µCi/mole of 65Zn, applied topically on four circular areas, 1 in. in diameter, on the saved skin on animal’s back


SAMPLE COLLECTION
- Analysis of skin: Treated skin areas were excised and fixed in cold alcoholic formalin


ANALYSIS
- Method type(s) for identification: Automatic Gamma Counter (Nuclear Chicago Model 4222 with a 3-in. sodium iodide crystal):


HISTOLOGY
- Blocks of the skin were routinely processed & embedded in paraffin; 6 µm sections were taken and stained with heamtoxylin and eosin.
- Blank slides coated with emulsion, developed and fixed in a similar fashion were used as controls for checking the background fog.
- Zinc was localized histochemically by the diphenylthiocarbazone method. Sulfhydryl (-SH) and disulfide (-SS) groups were localized using alkaline tetrazolium method. 0.1 M n-ethyl maleimide in 0.1 M phosphate buffer was used at pH 7.4 for blocking the sulfhydryl (-SH) groups.
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:
No data
Total recovery:
No data
Conversion factor human vs. animal skin:
No data

Any other information on results incl. tables

Radiocounts of 65Zn:

-Optimal activity was observed at 6 h after each application; reduced at 24 h after application of first or second dose (see table 1).

- High concentration was observed in the cortical and cuticular zones of the hair shaft, optimal in the keratogeous zone

- 65Zn localisation was very low in the epidermis, dermis and in blood vessels of both dermis and hypodermis

 

Histology:

- Optimal staining intensity was seen in the cortex of the hair shaft and in the keratogenous matrix of the hair papilla

Table 1. 65Zn Retention on excised skin blocks (cpm X 103)*

Compound

Total applied dose of Zn compound

Time after last application

6 h

24 h

Applied

Retained

%

Applied

Retained

%

Zinc oxide (Single dose)

2.5 mg

784

161

20.6

784

185

23.6

Zinc oxide (double dose)

2.5 mg

1478

314

21.2

1478

369

25.0

* Results corrected for background and counted simultaneously with an aliquot of the applied sample. Second dose was always applied 24 h after the first application.

Applicant's summary and conclusion

Conclusions:
Under the test conditions, percutaneous uptake of the zinc in rabbit skin was observed on topical application of the radioactive test material.
Executive summary:

ZnO, zinc omadine, zinc sulphate and zinc undecylenate (131mCi/mole of65Zn2+) were used for topical application on shaved skin on the back of rabbits. Each application consisted of 2.5 mg Zn-compound containing 5mCi65Zn2+. Two animals received one application on four skin areas left of the spine, while the four skin areas on the right side received two applications, the second one 24 hours after the first one. The rabbits were killed 6 and 24 hours after the second application. One rabbit served as control animal.

No significant differences were found in the amount and location of 65Zn2+in skin treated with 4 different zinc compounds. High concentrations of 65Zn2+were observed in the cortical and cutical zones of the hair shaft, being the highest in the keratogenous zone. Accumulation of65Zn2+in epidermis was very low but heavy in the subdermal muscle layer. Since no different rates of absorption and concentrations of zinc compounds with different oil/water solubility, pH, and molecular weight were seen, it was suggested that the major mode of65Zn2+uptake in skin is by diffusion through the hair follicles due to the heavy localization of65Zn2+primarily in the hair shaft and hair follicles. According to the investigators this emphasizes that chemical differences in the compounds may not play a very important role in the skin uptake of65Zn2+. No data were given on systemic absorption.