Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Landsteiner-Draize Method. No more information.
GLP compliance:
no
Type of study:
other: Landsteiner / Draize method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Aluminium oxide AK 43/79 and aluminium oxide AK 44/79
- Analytical purity: no data

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: albino SPF
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of laboratory Animals, TNO, Zeist, The Netherlands
- Age at study initiation: young adult
- Weight at study initiation: 276 - 348 g
- Housing: animals were individually housed in suspended stainless steel cages, fitted with wire mesh floors and fronts
- Diet : all animals were fed stock diet (produced by Hope Farms, Woerden, The Netherlands), ad libitum. The composition of the diet and Al content are not provided (not a critical omission).
- Water: tap water ad libitum
- Acclimation period: 3 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 24 ± 1°C
- Humidity (%): 45 ± 5%
- Photoperiod (hrs dark / hrs light): Artificial light was used 12 hours daily from 6 a.m. to 6 p.m.

Randomization: Animals were randomly assigned to 4 treatment groups – two test groups and two control groups with 8 animals in each group.

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
other: It was mentioned that both test compounds were administered as aqueous suspensions. No details were available on the preparation of test item for administration, however.
Concentration / amount:
The concentration 33.33% was selected based on the results of a preliminary study that showed that one intra-dermal injection of 0.1 ml of a 33.33% aqueous suspension induced a mild skin reaction. Therefore, a 33.33% dilution was used for the induction and challenge injections.
Challengeopen allclose all
Route:
intradermal
Vehicle:
other: It was mentioned that both test compounds were administered as aqueous suspensions. No details were available on the preparation of test item for administration, however.
Concentration / amount:
The concentration 33.33% was selected based on the results of a preliminary study that showed that one intra-dermal injection of 0.1 ml of a 33.33% aqueous suspension induced a mild skin reaction. Therefore, a 33.33% dilution was used for the induction and challenge injections.
No. of animals per dose:
Test groups: 8 animals;
Control group: 8 animals.
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10 intra-dermal injections
- Site: on the right flank within an area of 3 x 4 cm
- Frequency of applications: 3 times weekly for 3 weeks
- Concentrations: During the first injection, each animal received 0.05 ml of the administered solution, in the second to the tenth injections 0.1 ml was administered to each animal
- The injection sites were examined 24 hours after the injection.

B. CHALLENGE EXPOSURE
- Concentrations: 0.05 ml of the 33.33% diluted test sample
- Evaluation (hr after challenge): 2 weeks after the last injection
- The reaction sites were examined 24 hours after the injection.

OTHER:
Observations
Data on body weights, mortality and signs of systemic toxicity during the study are not available.

Skin reactions:
The test compounds caused mild (after 1 to 7 injections in 8 animals) to moderate (after 8 injection in 2 animals, after 9 injection in 4 animals and after 10 injections in 8 animals) skin reactions during the induction period.
Challenge controls:
The control animals were treated at the same time as test animals with 0.05 ml of the 33.33% dilution of the each test sample.
Positive control substance(s):
no

Results and discussion

Positive control results:
not applicable

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
33.33%
No. with + reactions:
8
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 33.33%. No with. + reactions: 8.0. Total no. in groups: 8.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
33.33%
No. with + reactions:
8
Total no. in group:
8
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 33.33%. No with. + reactions: 8.0. Total no. in groups: 8.0.

Any other information on results incl. tables

Test groups (8 animals)

AK 43/79

After the challenge dose of AK 43/79, all animals from this group developed a mild skin reaction.

 

AK 44/79

The challenge dose of AK 44/79 provoked mild reaction in 6 animals and moderate reaction in 2 animals.

 

Control group (8 animals)

AK 43/79 (controls)

After the challenge dose of AK 43/79, the control animals showed a mild reaction in 7 and a moderate reaction in 1 animal. 

 

AK 44/79 (controls)

The challenge dose of AK 44/79 provoked 7 mild reactions and 1 moderate reaction.

 

No significant differences were reported between both test compounds and the control animals with respect to the degree and incidence of erythema and oedema.

Individual data are provided in Table 1 and 2 of the report.

 

Table 1. Individual positive reactions (marked with + signs) observed during the induction and challenge period with AK 43/79

Test animals

Control animals

No.

Individual direct reaction

challenge

No.

Reaction to injection at the same time as the challenge

1

2

3

4

5

6

7

8

9

10

2278

+

+

+

+

+

+

+

+

+

++

+

2286

+

2279

+

+

+

+

+

+

+

++

++

++

+

2287

+

2280

+

+

+

+

+

+

+

+

+

++

+

2288

+

2281

+

+

+

+

+

+

+

++

++

++

+

2289

++

2282

+

+

+

+

+

+

+

+

++

++

+

2290

+

2283

+

+

+

+

+

+

+

+

+

++

+

2291

+

2284

+

+

+

+

+

+

+

+

++

++

+

2292

+

2285

+

+

+

+

+

+

+

+

+

++

+

2293

+

2298

 

+

+

+

+

++

++

++

++

++

+

2306

+

2299

+

+

+

+

+

++

++

++

++

++

+

2307

+

2300

+

+

+

+

+

+

++

+

++

++

++

2308

++

2301

+

+

+

+

+

+

++

++

++

++

+

2309

+

2302

+

+

+

+

+

++

++

++

++

++

+

2310

+

2303

+

+

+

+

+

++

++

++

++

++

+

2311

+

2304

+

+

+

+

+

+

++

++

++

++

+

2312

+

2305

+

+

+

+

+

++

++

++

++

++

++

2313

+

 Degree of reaction: + = mild; ++ = moderate

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Based on the reaction to the challenge dose, it can be concluded that Al oxide AK 43/79 and Aluminium oxide AK 44/79 has no sensitisation potential under the experimental conditions.
Executive summary:

The skin sensitisation potential of two samples aluminium oxide, namely aluminium oxide TBH: AK 43/79 and aluminium oxide TOF: AK 44/79, was assessed in guinea pigs (male albino SPF, 8 animals in each group) using the Landsteiner/Draize method (Central Institute for Nutrition and Food Research, Germany) at the request of Degussa AG, Germany (1979). Both compounds were administered by intra-dermal injections. A 33.3% aqueous suspension was used in both the induction and challenge phases. During the induction phase, the test animals received 10 intra-dermal injections of the test suspension, 3 times per week over a 3 week period. The test suspensions were administered to different shaved spots on the right flank of the animals within an area of 3 x 4 cm. The injected volume was 0.05 mL for the first injection and 1.0 mL for subsequent. The control group received a single injection during this phase. The injection sites were examined 24 hours after the injection and the diameter, colour and thickness of any lesions were used as criteria for the intensity of the reaction. In the induction phase,following 1 to 7 injections of AK 43/79, all animals showed mild reactions. Two animals showed moderate reactions after the 8th injection, an additional 2 animals showed moderate reactions after the 9th injection and all 8 animals showed a moderate reaction after the 10th injection. Data were provided on any skin reactions on the single injection received by the control animals. For AK 44/79, all reactions were mild until after the 6th injection when 5 animals showed a moderate reaction. All animals showed moderate reactions

after the 7th to 10th injections.  Two weeks after the last injection, guinea pigs from both test groups and the control group received the challenge dose in the amount of 0.05 mL per animal. The reaction sites were examined 24 hours after the injection.After the challenge dose of AK 43/79, all animals exposed during the induction period developed a mild skin reaction. A mild reaction was also found in 7 and a moderate reaction in 1 of the animals in the control group. The challenge dose of AK 44/79 provoked a mild reaction in 6 animals and moderate reaction in 2 animals exposed during the induction period. In the control animals, 7 mild reactions and 1 moderate reaction were observed. No significant differences were observed between the test and control animals with respect to the degree and incidence of erythema and oedema. Under the conditions of this test, aluminium oxide AK 43/79 and aluminium oxide AK 44/79 are not skin sensitizers (Landsteiner/Draize test, guinea pig).