Neodecanoic acid, zinc salt, basic

Dermal absorption

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 oxide, 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

Test material information

Constituent 1

Reference substance name:

Zinc oxide

EC Number:

215-222-5

EC Name:

Zinc oxide

Cas Number:

1314-13-2

Molecular formula:

ZnO

IUPAC Name:

oxozinc

Details on test material:

suspension of zinc oxide

Test animals

Species:

other: pig skin in vitro

Strain:

not specified

Sex:

not specified

Details on test animals or test system 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 ZnO at a concentration of 40 mg/ml in water, were 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 hours^a

	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 anin vitrotesting 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.