Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Results of the preliminary study are limited in their scope because the absorption rate could be affected by several conditions that were not included in this study. The most important conditions that differ from consumer use include the vehicle of delivery, the occlusive application, and the one-time application.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
A preliminary study of the dermal absorption of aluminium from antiperspirants using aluminium-26.
Author:
Flarend R, Bin T, Elmore D and Hem SL.
Year:
2001
Bibliographic source:
Food Chem Toxicol. 39(2):163-168.

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A study was performed to measure the dermal absorption of aluminium from a one-time application of aluminium chlorohydrate with the use of Accelerator mass spectrometry (AMS) and the isotope 26 Al.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Aluminium-26-labeled aluminium chlorohydrate (ACH)
Specific details on test material used for the study:
Aluminium-26-labeled aluminium chlorohydrate (ACH) was prepared by adding a very small amount of 26Al as 26AlCl3 solution to a larger amount of 27AlCl3 solution. Then, aluminium powder (27Al) was dissolved in the AlCl3 solution to produce the ACH.
Radiolabelling:
yes

Test animals

Species:
human
Sex:
male/female

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
Single dose
Doses:
- Nominal doses: 84 mg of labeled ACH (13.3 mg Al for male subject; 12.4 mg Al for female subject)
No. of animals per group:
Two adult volunteers (a male and a female subject)
Control animals:
no
Details on study design:
DOSE PREPARATION
- Method for preparation of dose suspensions: The original 26 Al-labeled ACH solution had a concentration of 42% (calculated assuming a dihydrate) and was diluted to 21% by the addition of deionized water.

APPLICATION OF DOSE: 0.4 mL of the 21% ACH solution was loaded into a syringe and applied to the left axilla surface of two adult volunteers (a male and a female subject).

TEST SITE
- Preparation of test site: For the 21 days prior to the application of the ACH and for the duration of the study, the subjects were requested not to use any underarm products on the axilla being tested. 2 days prior to the ACH application, the subjects shaved their axillae and just prior to the application, the area was washed using a damp cloth and mild soap then inspected to ensure it was free of nicks, scrapes or other broken skin.
- Area of exposure: left axilla surface
- % coverage: application area measured approximately 3 in. x 4 in.
- Type of cover / wrap if used: Once the applied ACH was dry, the area was covered with a large occlusive-type bandage with adhesive on the edge of the bandage.

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: Yes; During these first 6 days, the subjects were requested to refrain from any activity resulting in excessive sweating, not to swim or otherwise emerge the area in water, and to take precautions to keep the underarm as dry as possible when bathing.

REMOVAL OF TEST SUBSTANCE
- Each morning, for the next six mornings, the bandage was removed. Strips of tape were then applied to the axilla and removed to strip away dead skin and surface ACH. Each day, two strippings were performed on the entire application area and the area was then gently washed with commercial pre-wetted towelettes. The area was allowed to air-dry, and a new bandage was applied. The old bandage, tape strippings and the towelettes were placed in large self-sealing freezer bags and stored in a refrigerator until prepared for analysis.

SAMPLE COLLECTION
- Collection of blood: Blood samples were drawn before the ACH was applied and periodically for the following 7 week. Blood samples were drawn by venipuncture at 0, 6 and 14 h; 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 18, 24, 32, 42 and 53 days after the application of ACH.
- Collection of urine: 24 h urine samples were collected starting from the time of the application and also continuing periodically for the following 7 week. (24 h urine samples were collected for days 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, 8-9, 9-10, 10-11, 11-12, 13-14, 17-18, 23-24, 31-32, 41-42 and 52-53).

SAMPLE PREPARATION
- Blood samples were drawn in vacuum tubes with premeasured EDTA and refrigerated until prepared for analysis. Whole blood was combined with 2 mg aluminium-27 and prepared for analysis using acid digestion and oxine precipitation.
- Urine samples were preserved by the addition of 10-20% (by volume) concentrated nitric acid until they were prepared for analysis. Urine samples were concentrated by a factor of 5x by evaporation. Then aliquots of the concentrated urine were combined with 3-5 mg aluminium-27 and prepared for analysis as described elsewhere using acid digestion, and oxine precipitation (King et al., 1997).
- Bandage samples: The bandage samples (also containing the tape-strippings and washings) were prepared for AMS analysis by first drying at 150 °C for 30 min, and then ashing at 440 °C for 180 min in a porcelain bowl. The ashes were then redissolved in 5 N nitric acid and transferred to centrifuge tubes. The samples were then diluted to a concentration low enough to be measured by AMS. An aliquot of the final diluted sample was then combined with 4-20 mg aluminium-27 and prepared for analysis as described previously (Flarend and Elmore, 1997).

ANALYSIS
- Method type(s) for identification: Selected samples were analyzed by AMS at Purdue University’s PRIME Lab (Jackson et al., 1999) using a tandem accelerator operated at 5 MV. The amount of 26Al present in each sample was determined by measuring the 26Al:27Al ratio in the prepared samples.
- Selected urine samples were also measured for aluminium content using inductively coupled plasma-atomic emission spectrometry to find the amount of aluminium already present in the urine and not accounted for by the AMS preparation.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
yes
Absorption in different matrices:
- Bandage, tape-stripping and washing samples indicate that in the male subject at least 48 % (in 6 days) and in the female subject at least 31 % (in 4 days) of the applied aluminium was recovered from the skin surface. For both subjects, virtually all of this was in the first day (45 % for the male subject, and 30 % for the female subject).
- Blood: Aluminium-26 detected in the blood sample taken 6 h after application indicated that aluminium from ACH was being absorbed through the skin. Blood samples also indicate that aluminium from the applied ACH was still present in the blood at least 15 days after the application. The measured concentrations of 26 Al after the ACH was applied were increased from the concentrations which were measured just prior to the ACH being applied. Although 26Al from the labeled ACH could be detected in the blood of both subjects, the concentrations were too low for reliable quantitative determinations to be made. Thus, very few blood samples were actually measured and the quantitative analysis of the amount of aluminium absorbed was based on the urine data.
- Urine: Urine samples indicate that aluminium was absorbed and eliminated from the body during the first day following the ACH application, and continued for at least 44 days. Cumulative aluminium in urine, indicates that 0.0082 % (male subject) and 0.016 % (female subject) of the applied aluminium was eliminated in urine.
- As it has been reported (Priest et al., 1995) that 80-90 % of absorbed aluminium is eliminated in urine within a period of 1-40 days, a correction factor of 0.85 was used to estimate the amount of aluminium which was actually absorbed from the ACH. The factor of 2 in this equation accounts for the absorption of aluminium had the ACH been applied to both underarms.

Absorption of Al = (elimination of Al / 0.85) * 2

- Results indicate that only 0.012% of the applied aluminium was absorbed through the skin. At this rate, about 4 µg of aluminium is absorbed from a single use of ACH on both underarms. This is about 2.5% of the aluminium typically absorbed by the gut from food over the same time period.
Total recovery:
- Total recovery: Total aluminium found in the bandages, tapestrippings, washing samples and urinary excretion was 48 % of the applied dose for the female subject and 31 % for the male subject. Thus, total recovery was only 48 % and 31 %. The remaining 52 % or 69 % was either lost into the environment when the bandages came loose, or was retained as precipitated plugs in the sweat ducts.
Percutaneous absorption
Dose:
84 mg of the labeled ACH
Parameter:
percentage
Absorption:
0.012 %
Remarks on result:
other: 6 days
Remarks:
At this rate, about 4 µg of aluminium is absorbed from a single use of ACH on both underarms.
Conversion factor human vs. animal skin:
Not applicable

Any other information on results incl. tables

Table 7.1.2/1: Absorption and elimination of aluminium following the dermal application of aluminium chlorohydrate

Subjects

Aluminium applied (mg)

Aluminium recovered from skin (mg)

Aluminium eliminated in urine (µg)

*Aluminium absorbed through skin (µg)

Male subject

13.3

6.3

1.1

2.6

Female subject

12.4

3.8

1.9

4.5

Average

12.9

5.1

1.5

3.6

* Absorption corrected for 85% complete renal elimination and application of ACH to both underarms.

Applicant's summary and conclusion

Conclusions:
Results indicate that only 0.012% of the applied aluminium was absorbed through the skin. At this rate, about 4 µg of aluminium is absorbed from a single use of ACH on both underarms. This is about 2.5% of the aluminium typically absorbed by the gut from food over the same time period. Therefore, a one-time use of ACH applied to the skin is not a significant contribution to the body burden of aluminium. To further demonstrate the safe use of antiperspirants, it must now be verified that neither frequent use, method of delivery, specific formulation, nor physical activity increases the absorption of aluminium from antiperspirants to a level which could be deemed hazardous.
Executive summary:

In a dermal absorption study, 84 mg of Aluminium-26-labeled aluminium chlorohydrate (13.3 mg Al for male subject; 12.4 mg Al for female subject) was applied to a single underarm of two adult subjects under occlusive conditions. Blood and urine samples were collected over 7 weeks to determine the aluminium concentration using Accelerator mass spectrometry (AMS). Tape-stripping and mild washings of the skin were also collected for the first 6 days. 

Total aluminium found in the bandages, tape-strippings, washing samples and urinary excretion was 48 % of the applied dose for the female subject and 31 % for the male subject. Thus, total recovery was only 48 % and 31 %. Results indicate that only 0.012% of the applied aluminium was absorbed through the skin. At this rate, about 4 µg of aluminium is absorbed from a single use of ACH on both underarms. This is about 2.5% of the aluminium typically absorbed by the gut from food over the same time period. Therefore, a one-time use of ACH applied to the skin is not a significant contribution to the body burden of aluminium.