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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
No data
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Study was not conducted according to a guideline or under GLP conditions. Detailed methods and results not reported.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Pathological Changes Associated with Aluminum and Zirconium Compounds
Author:
Prior JT and Cronk GA.
Year:
1959
Bibliographic source:
Arch Dermatol. 80:447-454.

Materials and methods

Test guideline
Qualifier:
no guideline followed
GLP compliance:
no
Remarks:
pre-GLP
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): Aluminum chlorohydroxide complex, 22 %

Test animals

Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 4 months
- Weight at study initiation: 1500-2500 g

Administration / exposure

Type of coverage:
not specified
Vehicle:
not specified
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
No data
Frequency of treatment:
No data
Doses / concentrations
Remarks:
Doses / Concentrations:
Subcutaneous: 110 mg; intracutaneous: 22 mg of Aluminum chlorohydroxide complex, 22 %
Basis:
nominal per unit area
No. of animals per sex per dose:
No data
Control animals:
no
Positive control:
None

Examinations

Observations and examinations performed and frequency:
- Reactions from the injections were measured after 24 and 48 h, 1, 2, 3 and 4 weeks. The diameter of the inflammatory infiltrate was determined and used as an index of the severity of the reaction.
- Biopsy specimens were taken at intervals to correlate the gross and microscopic findings.
Other examinations:
None
Statistics:
None

Results and discussion

Results of examinations

Clinical signs:
not examined
Dermal irritation:
effects observed, treatment-related
Mortality:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Details on results:
Acute inflammatory reactions with tissue necrosis and ulceration were noted in association with the subcutaneous and intracutaneous injection of the aluminum compounds. There was a more marked reaction at the injection sites in areas that had been previously injured. Repeated injections, either subcutaneously or intracutaneously, resulted in the same type of cutaneous ulcers, but these were not felt to be more severe than those following the original injections. Granulomas were seen only after the subcutaneous injection of aluminum chlorohydroxide complex. All lesions went on to normal, although delayed, healing. The percutaneous application of these chemical compounds failed to produce any significant lesions.
- See the attached document for detailed results.

Effect levels

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

See the attached document for tables of results

Applicant's summary and conclusion

Conclusions:
Acute inflammatory reactions with tissue necrosis and ulceration were noted in association with the subcutaneous and intracutaneous injection of the aluminum compounds. There was a more marked reaction at the injection sites in areas that had been previously injured. Repeated injections, either subcutaneously or intracutaneously, resulted in the same type of cutaneous ulcers, but these were not felt to be more severe than those following the original injections. Granulomas were seen only after the subcutaneous injection of aluminum chlorohydroxide complex. All lesions went on to normal, although delayed, healing. The percutaneous application of these chemical compounds failed to produce any significant lesions.
Executive summary:

Study was conducted to determine the tissue reactions to subcutaneous and intracutaneous injections and to percutaneous application of a variety of aluminum salts. Aluminum salts were administered as follows:

Subcutaneous (0.5 mL), using the skin of the rabbit's back; intracutaneous (0.1 mL), using the skin on the inner aspect of the rabbit's ear; percutaneous using cotton pads saturated with test solution and held to the skin of the rabbit’s ear by Scotch tape. The three basic routes of administration were modified further by being applied to intact undamaged skin, damaged skin and finally by repeated applications.

Aluminum chlorohydroxide complex, 22 %: Subcutaneous - 110 mg; intracutaneous - 22 mg

Aluminum sulfate, 17 %: Subcutaneous - 85 mg; intracutaneous - 17 mg

 

Acute inflammatory reactions with tissue necrosis and ulceration were noted in association with the subcutaneous and intracutaneous injection of the aluminum compounds. There was a more marked reaction at the injection sites in areas that had been previously injured. Repeated injections, either subcutaneously or intracutaneously, resulted in the same type of cutaneous ulcers, but these were not felt to be more severe than those following the original injections. Granulomas were seen only after the subcutaneous injection of aluminum chlorohydroxide complex. All lesions went on to normal, although delayed, healing. The percutaneous application of these chemical compounds failed to produce any significant lesions.