Dialuminium chloride pentahydroxide

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 November 1996 - 29 November 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to Draft OECD guideline for in vitro cutaneous penetration and under GLP conditions.

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:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 428 (Skin Absorption: In Vitro Method)

Deviations:

yes

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Aluminiumchlorohydrate
- Substance type:
Three different formulations:
Antitranspirant Roll-on
Deo Creme
Deo Roll-on
- Composition of test material, percentage of components:
Antitranspirant Roll-on: Aqueous-ethanolic solution with 8% content of active ingredient (about 61% water, 24% ethanol and 5% polypropyleneglycol)
Deo Creme: Emulsion with 10% content of active ingredient (64% water, remainder propyleneglycol, fatty alcohol, paraffin, glyceride)
Deo Roll-on: Emulsion with 7.5% content of active ingredient (78% water, remainder isopropylmyristat and ethoxylized fatty alcohols)
- Lot/batch No.: Confidential information

Radiolabelling:

no

Test animals

Species:

pig

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

Not relevant

Administration / exposure

Type of coverage:

open

Vehicle:

other: three different formulations

Duration of exposure:

24 hours

Doses:

- Nominal doses: 2.5 mg/cm2
- Dose volume: 10 ul
- Rationale for dose selection: Corresponds well with the human use situation (average quantity of 500 mg deodorant is assumed to be applied on an area of 400 cm2)

No. of animals per group:

Not relevant

Control animals:

no

Remarks:

not relevant

Details on study design:

Not relevant

Details on in vitro test system (if applicable):

SKIN PREPARATION
- Source of skin: Local butcher
- Ethical approval if human skin: Not relevant
- Type of skin: back and flank of male, castrated pig
- Preparative technique:
Skin cleaned with tap water under a shower. Bristles cut with an electric cutter. Skin surface shortly washed with 70% ethanol and blotted with soft household paper and then stored for approximately 16 hours at 4 Degrees Celsius in a refrigerated room. Strips measuring 7.5x40 cm cut out with a scalpel and marked for identification of the initial position. Subcutaneous fat removed with electrical knife using a guide of 4 mm thickness. In the next step a 1 mm thick layer of the skin strips was cut off using an air-driven high speed dermatome. Skin strips were made up of the horny layer, epidermis, part of the dermis but no subcutaneous fat.
- Thickness of skin (in mm): 1 mm
- Membrane integrity check: Tested prior to each experiment. 3.648 ml of a 1% solution of caffeine in aquadest applied on the skin for five hours. Collection vessels were changed every hour and the caffeine content was measured by HPLC analysis. After 5 hours the caffeine-solution was aspirated and the skin blotted dry with Kleenex tissue. Permeation of a maximum of 0.2% per hour of the applied total amount into the receptor fluid is accepted as criterion for the integrity of the skin.
- Storage conditions: Used immediately or sealed in plastic bags and stored frozen in a flat, horizontal position at -20 Degrees Celsius for up to one year

PRINCIPLES OF ASSAY
- Diffusion cell: Permeation chamber system in incubator with surface of 9.6 cm2
- Receptor fluid: ?
- Solubility od test substance in receptor fluid:
- Flow-through system: Multichannel pump outside the incubator distributes receptor fluid to chambers from collection vessels and back. Flow rate was regulated to deliver 5 ml/hour to the chamber system.
- Test temperature: 32-33 Degrees Celsius
- Humidity: 50-60%
- Occlusion: Air exposure of stratum corneum

Results and discussion

Absorption in different matrices:

Antitranspirant Roll-on:
- Skin wash: 84.0-108.1%
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): Test substance could not be detected up to the detection limit of 0.01 ug/ml
- Skin preparation (in vitro test system): Remainder in horny layer: 1.70-5.80%
- Stratum corneum (in vitro test system): 0.40-0.90%

Deo Creme:
- Skin wash: 95.1-108.8%
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): Test substance could not be detected up to the detection limit of 0.01 ug/ml
- Skin preparation (in vitro test system): Remainder in horny layer: 1.50-5.70%
- Residual skin (in vitro test system): 0.70-4.30%

Deo Roll-on:
- Skin wash: 93.8-122.8%
- Receptor fluid, receptor chamber, donor chamber (in vitro test system): Test substance could not be detected up to the detection limit of 0.01 ug/ml
- Skin preparation (in vitro test system): Remainder in horny layer: 3.0-9.10%
- Residual skin (in vitro test system): 0.10-2.80%

Total recovery:

Antitranspirant Roll-on:
- Total recovery: 86.9-110.5% (103.3 +/- 9%)
- Recovery of applied dose acceptable: No, total recovery does not match the criteria outlined in OECD 428 (100 +/- 10%), as the lower recovery percentage is below 90% and the upper percentage is slightly above 110%
- Results adjusted for incomplete recovery of the applied dose: No
- Limit of detection (LOD): 0.01 ug/mL (receptor fluid)
- Quantification of values below LOD or LOQ: No test substance detected in receptor fluid (<0.01 ug/mL)

Deo Creme:
- Total recovery: 100.6-115.2% (105.4 +/- 5.1%)
- Recovery of applied dose acceptable: No, total recovery does not match the criteria outlined in OECD 428 (100 +/- 10%), as the upper percentage is above 110%
- Results adjusted for incomplete recovery of the applied dose: No
- Limit of detection (LOD): 0.01 ug/mL (receptor fluid)
- Quantification of values below LOD or LOQ: No test substance detected in receptor fluid (<0.01 ug/mL)

Deo Roll-on:
- Total recovery: 100.9-131.3% (115.5 +/- 10.9%)
- Recovery of applied dose acceptable: No, total recovery is does not match the criteria outlined in OECD 428 (100 +/- 10%), as the upper percentage is above 110%
- Results adjusted for incomplete recovery of the applied dose: No
- Limit of detection (LOD): 0.01 ug/mL (receptor fluid)
- Quantification of values below LOD or LOQ: No test substance detected in receptor fluid (<0.01 ug/mL)

Percutaneous absorption

Percutaneous absorption 1

Dose:

2.5 mg/cm2

Parameter:

percentage

Absorption:

ca. 0 %

Remarks on result:

other: 72h

Remarks:

Antitranspirant Roll-on

Percutaneous absorption 2

Dose:

2.5 mg/cm2

Parameter:

percentage

Absorption:

ca. 0 %

Remarks on result:

other: 72h

Remarks:

Deo Creme

Percutaneous absorption 3

Dose:

2.5 mg/cm2

Parameter:

percentage

Absorption:

ca. 0 %

Remarks on result:

other: 72h

Remarks:

Deo Roll-on

Conversion factor human vs. animal skin:

Taking into account the highest amounts found in the horny layer and in the residual skin in the experiment with Deo-Creme the absorption will be 3.53 ug/cm2 (5.7% of applied dose, mean of six skins). Human armpit area: 400 cm2, mean body weight: 60 kg. Result: 23.6 ug/kg bw uptake.

Any other information on results incl. tables

The collected volumes of the receptor fluid show that in the experiments between 5.10 and 5.60 (antitranspirant) and 5.40 to 5.50 ml receptor fluid (Deo Roll-on and Deo Creme) per hour were aspirated and drawn through the flow-trough chambers.

Skin integrity was tested in all three independently performed experiments. Cumulative amounts of caffeine in receptor fluid were <0.03% to 0.10% of the applied dose. The demand of the draft OECD guideline to use a minimum of four cells with similar skin integrity could therefore be fullfilled.

Applicant's summary and conclusion

Conclusions:

This study found that Aluminiumchlorohydrate does not penetrate pig skin well, the article was undetectable in recepter fluid and only minor percentages of the applied dose were found in the horny layer and/or residual skin. In worst case an uptake of 3.53 ug/cm2 (5.7%) was found, resembling an uptake of 23.6 ug/kg bw for humans.

Executive summary:

Three different formulations of alumniumchlorohydrate (antitranspirant Roll-on, an aqueous-ethanolic solution with 8% contect of active ingredient; Deo Creme, an emulsion with 10% contect of active ingredient; Deo Roll-on, an emulsion with 7.5% active ingredient) were tested for cutaneous penetration and absorption through pig skin in vitro. Skin preparations measuring 1000 um in thickness with stratum corneum, stratum germinativum and blood-vessel-containing parts of the dermis were obtained from pigs using a modified dermatome.

 

Subsequently in three independent experiment for each formulation six skin preparations were mounted in Teflon diffusion chamers which were continously rinsed with physiological receptor fluid. After checking the flow rate and carrying out a skin integrity test using the marker substance caffeine, the test formulations were applied to each skin at a dose of 10 mg/4 cm2 in a practive-relevant manner for 24 hours and subsequently washed off with a neutral shampoo.

 

After 0, 16, 24, 40, 48, 56 and 72 hours, the cutaneous permeation of Aluminium chlorohydrate was determined by quantifying aluminium with atomic absorption analysis in the receptor fluid. Furthermore, to check the experiment conditions, Aluminiumchlorohydrate was analysed in the horny layer, residual skin and the rinsing fluids.

 

In each experiment the integrity of the skin membranes used could be demonstrated by HPLC analysis with cumulative amounts over five hours with <0.03% to 0.10% of the applied caffeine dose, which lay under the limit of 0.2% per hour of the total caffeine dose applied. Thus, the demand of the draft of the OECD-guideline to use a minium of four cells with similar integrity could be fullfilled in each experiment.

 

It was found that in each experiment no Aluminium passed through the skin barrier up to the detection limit of <0.010 ug/ml at collection time of 0, 16, 24, 40, 48, 64 and 72 hours. After extraction, only small quantities of Aluminium could be detected in the horny layer and in the residual skin. In each experiment the greater part of the substance was recovered in the rinsing solution with average recovery rates of about 95 -100% of the dose applied.

 

It is concluded that the cutaneous permeation of Aluminium is in each case less than 0.022% of the applied dose. Taking into consideration the highest average amounts found in the horny layer and residual skin in the experiment with Deo-Creme, the above value will rise to 3.53 ug/cm2. With a humans armpoit areas of 500 cm2 and a mean body weight of 60 kg, this would result in an updatke of 23.53 ug per kg body weight.

 

This is a worst-case assumption, because Aluminium could not be detected in the receptor fluid up to the detection limit even after a collection time of 72 hours.