Registration Dossier

Administrative data

Endpoint:
dermal absorption in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given

Data source

Reference
Reference Type:
publication
Title:
A preliminary study of the dermal absorption of aluminium from antiperspirants using aluminium-26.
Author:
Flarend et al.
Year:
2001
Bibliographic source:
Food Chem Toxicol 2001; 39: 163-168.

Materials and methods

Test guideline
Qualifier:
no guideline required
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 26Al-labeled aluminium chlorohydrate - Analytical purity: no data
Radiolabelling:
yes
Remarks:
26Al

Test animals

Species:
human
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Not applicable.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Duration of exposure:
Single exposure
Doses:
21% ACH- The male had 13.3 mg Al applied containing 162 pCi of 26Al.- The female had 12.4 mg Al applied containing 151 pCi 26Al.
No. of animals per group:
Not applicable. (1 male and 1 female volunteer)
Control animals:
no
Details on study design:
Further Details on Administration:Subjects were requested not to use underarm products on the left axilla for 3 weeks prior to the study. 2 days prior to the study, the subjects shaved their axillae with an electric razor. Just prior to application of the ACH, the left axilla of each subject was washed with a damp cloth and mild soap and inspected for abrasions/nicks (none found).After the ACH had been applied and left to dry, the area was occluded with a bandage with adhesive edges that did not contact the area of ACH application. Sampling:26Al retained on/in surface layers of skin:Each morning for the next 6 days strips of tape were applied to the axilla and then stripped away. This was done twice and then the area gently washed with towelettes– the bandage, tape strippings and towelettes were sealed in freezer bags and stored in a refrigerator until analysis. During these 6 days, the subjects were asked to avoid activities that caused excessive sweating, not to swim or submerge the area of application in water and to avoid getting the underarm area wet when washing.The female subject developed a mild irritation to the bandage adhesive; by 48 hours after application of the ACH the skin was broken and ‘New Skin’ was applied to try to seal the surface and prevent enhanced absorption of the ACH. Despite the use of larger bandages, use of bandages had to be stopped in the female subject after 4 days. The male subject developed only mild irritation by day 5/6. The authors also reported that the bandages became loose at some points.Blood samples:Blood samples were taken by venipuncture before ACH application (0 hours) and also at 6 and 14 hours post-application; then on days 1,2,3,4,5,6,7,9,11,14,18,24,32,42 and 53 after application. The volume was not reported. They were taken into vacuum tubes with premeasured EDTA and refrigerated until analysis. Whole blood samples were combined with 2 mg 27Al and prepared for analysis by acid digestion and oxine precipitation.Urine samples:24 hour urine samples were collected daily for the first 11 days after application; then from days 13 to 14, 17 to 18, 23 to 24, 31 to 32, 41 to 42, and 52 to 53. The samples were preserved using 10-20% (by volume) conc. HNO3. Prior to analysis, the samples were concentrated by a factor of 5 by evaporation; combined with 3-5 mg 27Al and prepared for analysis by acid digestion and oxine precipitation.Chemical Analyses: 26Al in the samples was determined by accelerator mass spectrometry (AMS; tandem accelerator at PRIME lab, Purdue University; 5MV) using the 26Al/27Al ratio.ICP-MS was used to measure Al levels in a subset of urine samples (criteria used for selection of the subset were not specified) to ensure that the amount of Al in the urine would not influence the results from the AMS analyses.
Details on in vitro test system (if applicable):
Not applicable.

Results and discussion

Signs and symptoms of toxicity:
not specified
Dermal irritation:
not specified
Absorption in different matrices:
26Al recovered from the skin:Based on the amounts of 26Al in the bandages, tapes and towelettes, 48% of the Al applied to the underarm of the male subject was recovered from the skin surface in 6 days; 31% was recovered in 4 days in the female subject.26Al in blood:Levels of 26Al in the blood showed a clear increase after the application of ACH and could still be detected 15 days after application. Although 26Al could be detected in the blood, the levels were too low for reliable estimation of the % absorbed.26Al in urine:Results showed that 0.0082% of the estimated absorbed 26Al was eliminated in the urine of the male subject and 0.016% in the urine of the female subject. A correction factor of 0.85 was applied (assumes 80 to 90% of absorbed aluminium is eliminated in urine over the period of 40 days (Priest et al. 1995; Hum Exp Toxicol 14: 287-293 cited) and a factor of 2 to account for two underarms.
Total recovery:
No data.
Percutaneous absorptionopen allclose all
Dose:
12.4 mg
Parameter:
percentage
Absorption:
0.016 %
Remarks on result:
other: day 4
Remarks:
for the female volunteer (based on urine measurements)
Dose:
13.3 mg
Parameter:
percentage
Absorption:
0.008 %
Remarks on result:
other: day 6
Remarks:
for the male volunteer (based on urine measurements)
Conversion factor human vs. animal skin:
No data.

Applicant's summary and conclusion

Conclusions:
Aluminium is absorbed into the systemic circulation on single application with occlusion of aluminium chlorohydrate to underarms. Based on urine measurements, 0.01% of the applied aluminium was absorbed showing that aluminium does not cross the dermal barrier effectively.
Executive summary:

Flarend et al. (2001) studied the uptake of aluminium from aluminium chlorohydrate-containing antiperspirant using 26Al as a tracer. The study was carried out using two human volunteer subjects, one male and one female. 0.4 mL of 21% 26Al-ACH solution was applied to an area 3”x4” in the left axilla of the two volunteers. Application was done using a pre-soaked (deionized water) cotton swab. The area was allowed to air dry afterwards. After the ACH had been applied and left to dry, the area was occluded with a bandage with adhesive edges that did not contact the area of ACH application. Each morning for the next 6 days strips of tape were applied to the axilla and then stripped away, the area gently washed with towelettes–and the bandage, tape strippings and towelettes sealed in freezer bags and stored in a refrigerator until analysis. The female subject developed a mild irritation to the bandage adhesive that required cessation of their use after 4 days. Blood samples were taken by venipuncture before ACH application (0 hours) and also at 6 and 14 hours post-application; then on days 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 18, 24, 32, 42 and 53 after application. Twenty-four hour urine samples were collected daily for the first 11 days after application; then from days 13 to 14, 17 to 18, 23 to 24, 31 to 32, 41 to 42, and 52 to 53. The samples were preserved using 10-20% (by volume) conc. HNO3. 26Al in the samples was determined by accelerator mass spectrometry. ICP-MS was used to measure Al levels in a subset of urine samples to ensure that the amount of Al in the urine would not influence the results from the AMS analyses. Based on the amounts of 26Al in the bandages, tapes and towelettes, 48% of the Al applied to the underarm of the male subject was recovered from the skin surface in 6 days; 31% was recovered in 4 days in the female subject. Levels of 26Al in the blood showed a clear increase after the application of ACH and 26Al could still be detected 15 days after application. Although 26Al could be detected in the blood, the levels were too low for reliable estimation of the % absorbed. Results showed that 0.0082% of the estimated absorbed 26Al was eliminated in the urine of the male subject and 0.016% in the urine of the female subject. A correction factor of 0.85 was applied (assumes 80 to 90% of absorbed aluminium is eliminated in urine over the period of 40 days (Priest et al. 1995; Hum Exp Toxicol 14: 287-293 cited) and a factor of 2 to account for two underarms. In conclusion, aluminium is absorbed into the systemic circulation on single occluded application of aluminium chlorohydrate to underarms. Based on urine measurements, 0.01% of the applied aluminium was absorbed showing that aluminium does not cross the dermal barrier effectively.