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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:
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:
Zinc Absorption Through Skin: Correction of Zinc Deficiency in the Rat
Author:
Keen CL, Hurley BS & Hurley LS
Year:
1977
Bibliographic source:
Am. J. Clin. Nutr. 30: 528-530

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The plasma zinc level was measured after topical application of zinc chloride in pregnant rats consuming a diet deficient in zinc.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Zinc chloride
Radiolabelling:
no

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Simonsen Labs, Gilroy, Calif
- Housing: Housed individually in stainless steel cages
- Diet: Purified diet containing adequate zinc (100 ppm) before mating and purified diet deficient in zinc (less than 0.4 ppm) after mating during whole experimental period; ad libitum
- Water: Distilled deionized water; ad libitum

Administration / exposure

Type of coverage:
other: Covered with gauze and bandaged
Vehicle:
corn oil
Duration of exposure:
8 or 24 h
Doses:
0.4 mL of oil preparation containing 7,500 ppm zinc (as zinc chloride)
No. of animals per group:
5-7
Control animals:
yes
Details on study design:
STUDY DESIGN: Females were mated with males night before experimental day. Copulation was determined by the presence of sperm in the vaginal
smear next morning. The animals were divided into following five groups:
-Normal control (1 group): Sacrificed at the beginning of the experiment (time zero) to obtain representative plasma zinc levels of animals consuming an adequate zinc diet.
-Untreated and fed zinc-deficient diet (2 groups): Oil preparation (containing less than 4 ppm zinc) applied for the full 24 h in one group, and for the last 8 h in the other.
-Treated and fed zinc-deficient diet (2 groups): Same as above except that zinc chloride was added to oil.

TEST SITE
- Preparation of test site: Test sites (dorsal thoracic surface along the spinal axis) treated with a depilatory agent to remove a patch of hair (approximately 3 x 4 cm2).
- Type of cover / wrap if used: Covered with gauze and bandaged

CONTROL FOR INGESTION: As a control for the possibility of oral intake of zinc, Oil Red O was added as a marker so that any oil seeping through the bandages would be seen.

SAMPLE COLLECTION
- Terminal procedure: Sacrificed with ether after 24 h
- Collection of blood: Cardiac puncture
PLASMA ZINC ANALYSIS
- Method type(s) for identification: Atomic absorption spectrophotometry
- Limits of detection: 0.02 ppm zinc


Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
Plasma:
Untreated and zinc-deficient diet group:
-8 and 24 h application: Plasma zinc values significantly lower than all other groups after 24 h in both the groups

Treated and zinc-deficient diet group:
-8 h application: Plasma zinc values similar to those of the control group fed an adequate zinc diet and significantly higher than those of rats that received no zinc application to the skin.
-24 h treatment: Plasma zinc values significantly higher than in any other group, including normal controls (See Table 1 for details)
Total recovery:
Not determined
Percutaneous absorption
Remarks on result:
other: Not determined
Conversion factor human vs. animal skin:
Not applied

Any other information on results incl. tables

Table 1. Influence of topical zinc chloride on plasma zinc

 

Diet and topical application

Treatment time (h)

Rats (no.)

Plasma zinc

(µg/100 mL)

 

Time

Total duration

 

 

Control diet

0

0

5

114.6 ± 5.2*

Zinc-deficient diet

 

 

 

 

Oil

16-24

8

5

74.6 ± 2.5

Oil

0-24

24

6

63.2 ± 3.2

Oil + Zinc

16-24

8

7

114.8 ± 3.7*

Oil + Zinc

0-24

24

6

182.5 ± 8.9* # @

*Significantly higher than groups receiving oil without zinc, P < 0.001

#Significantly higher than the group receiving oil plus zinc for 8 hr, P < 0.001

@Significantly higher than control group, P < 0.001

Other data: There was no trace of Oil Red O stain in the area outside of the bandage in any of the animals tested, indicating that leakage did not occur. Therefore, the possibility of oral intake of zinc was discounted. Food intake was similar among all groups.

Applicant's summary and conclusion

Conclusions:
In conclusion, zinc was absorbed in clinically significant amount after topical application of zinc chloride in pregnant rats consuming a zinc-deficient diet.
Executive summary:

The effect (effect on plasma zinc concentration) of topical administration of zinc chloride was tested in pregnant rats consuming a diet deficient in zinc.

 

Four groups of rats were fed a zinc-deficient diet for 24 h. Half of the animals were treated during this period with a topical application of oil saturated with zinc chloride, for the full 24 h in one group, and for the last 8 h in the other. In the remaining two groups, oil without zinc chloride was applied under the same conditions as described above, and in all cases oral ingestion of the supplement was prevented. At the end of the 24 h period, the animals were sacrificed and plasma zinc was determined. An additional group of animals consuming a diet adequate in zinc was sacrificed without any treatment to provide control values of normal plasma zinc.

 

Rats consuming the deficient diet and without topical zinc supplementation had plasma zinc values significantly lower than all other groups after 24 h. Animals receiving zinc supplementation for 8 h had plasma levels similar to those of the control group fed an adequate zinc diet and significantly higher than those of rats that received no zinc application to the skin. In animals in which zinc was applied for 24 h, plasma zinc values were significantly higher than in any other group, including normal controls.

 

In conclusion, zinc was absorbed in clinically significant amount after topical application of zinc chloride in pregnant rats consuming a zinc deficient diet.