Zinc diricinoleate

Dermal absorption

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.

Justification for data waiving:

other:

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:

Unnamed

Year:

1974

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

Test material information

Constituent 1

Reference substance name:

Zinc oxide

EC Number:

215-222-5

EC Name:

Zinc oxide

Cas Number:

1314-13-2

IUPAC Name:

oxozinc

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 or test system 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 on systemic absorption. Concentration of 65 Zn in skin layers was determined.

Percutaneous absorption

Dose:

Not applicable

Remarks on result:

other: Not applicable

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: 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 of ⁶⁵Zn²⁺) were used for topical application on shaved skin on the back of rabbits. Each application consisted of 2.5 mg Zn-compound containing 5 mCi ⁶⁵Zn^{2 +}. 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  ⁶⁵Zn^{2 +} in skin treated with 4 different zinc compounds. High concentrations of  ⁶⁵Zn^{2 +} were observed in the cortical and cutical zones of the hair shaft, being the highest in the keratogenous zone. Accumulation of ⁶⁵Zn^{2 +} 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 of ⁶⁵Zn^{2 +} uptake in skin is by diffusion through the hair follicles due to the heavy localization of ⁶⁵Zn^{2 +} 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 of ⁶⁵Zn^{2 +}. No data were given on systemic absorption.