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Toxicological information

Dermal absorption

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Administrative data

Endpoint:
dermal absorption in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Industry initiated study, accepted for EU risk assessment for zinc sulphate, reliable study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999

Materials and methods

Principles of method if other than guideline:
cutaneous penetration and absorption through pig skin in vitro
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
solution of ZnSO4 monohydrate

Test animals

Species:
other: pig skin in vitro
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
not applicable

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Duration of exposure:
see results section
Doses:
not applicable
No. of animals per group:
not applicable
Details on study design:
see reference
Details on in vitro test system (if applicable):
A solution of ZnSO4 monohydrate at a concentration of 40 mg/ml in water, was tested for cutaneous penetration and absorption through pig skin in vitro. Skin preparations measuring 1 mm in thickness with stratum corneum, stratum germinativum and blood-vessel-containing parts of the dermis were obtained from pigs using a modified dermatome.

Results and discussion

Signs and symptoms of toxicity:
not examined
Dermal irritation:
not examined
Absorption in different matrices:
Dermal absorption of Zn (% of dose) through pig skin in vitro within 72 hours of ZnSO4 application:
receptor fluid: 0.3%, horny layer: 1.3%, residual skin: 0%, potentially absorbed dose: 1.6%
Total recovery:
Total recoveries of applied zinc ranged from 82.0 to 109.6%
Conversion factor human vs. animal skin:
see results

Any other information on results incl. tables

Table 1 Dermal absorption of Zn (% of dose) through pig skin in vitro within 72 hoursa

 

ZnSO4

ZnO

Receptor fluid

0.3 %

0.03 %

Horny layer

1.3 %

12.3 %

Residual skin

0 %

2.6 %

Potentially absorbed dose

1.6%

14.9%

aCorrected for background levels of zinc in receptor fluid and skin.

Applicant's summary and conclusion

Conclusions:
The authors concluded that dermal penetration of zinc was below 1% based on the cumulative amount recovered from the receptor fluid at 72 hours. However, the amount retained in the skin should be regarded as being absorbed because it may become available at a later stage. Hence, the rapporteur concludes that the dermal absorption of zinc from a solution of zinc sulphate monohydrate and a suspension of zinc oxide in this in vitro system may amount to 1.6% and 14.9%, respectively.
Executive summary:

Industry initiated an in vitro testing programme on two representative zinc compounds (zinc oxide and zinc sulphate) for percutaneous absorption (Grötsch, 1999). In this study, a solution of ZnSO4monohydrate and a suspension of ZnO, each at a concentration of 40 mg/ml in water, were tested for cutaneous penetration and absorption through pig skinin vitro. Skin preparations measuring 1 mm in thickness with stratum corneum, stratum germinativum and blood-vessel-containing parts of the dermis were obtained from pigs using a modified dermatome.In two independent experiments for each compound seven skin preparations were mounted in Teflon flow-through diffusion chambers which were continuously rinsed with physiological receptor fluid (0.9% NaCl in aqua bidest with antibiotics). After an integrity check using the marker substance caffeine, each of the test formulations were applied to six skins at a dose of 1 mg/cm2for 8 hours without occlusion, and subsequently washed off with a neutral shampoo. After 0, 2, 4, 6, 8, 16, 24, 40, 48, 64 and 72 hours, the cutaneous permeation was determined by quantifying zinc with atomic absorption spectroscopic analysis (detection limit: 10 ng/ml) in the receptor fluid. The experiment was stopped at 72 hours. Furthermore, zinc was analysed in the skin preparations and the rinsing fluids. In addition, blanks were measured in an unloaded control chamber.

Total recoveries of applied zinc in both experiments ranged from 82.0 to 109.6%. The results of analysis of the receptor fluid used and of the blank chambers without topical application of zinc compounds indicated that both the receptor fluid and porcine skin contain an intrinsic level of zinc. The amounts of zinc detected in receptor fluid and different layers of the skin were therefore corrected for background levels.

The authors concluded that dermal penetration of zinc was below 1% based on the cumulative amount recovered from the receptor fluid at 72 hours. However, the amount retained in the skin should be regarded as being absorbed because it may become available at a later stage. Hence, the rapporteur concludes that the dermal absorption of zinc from a solution of zinc sulphate monohydrate and a suspension of zinc oxide in thisin vitrosystem may amount to 1.6% and 14.9%, respectively.