Aluminium oxide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

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

Justification for non-LLNA method:

The study was conducted prior to the current requirement in Regulation (EC) 1907/2006 to perform a LLNA study (OECD 429) as the preferred in vivo skin sensitisation study.

Test material

Test material information

Constituent 1

Reference substance name:

Aluminium oxide

EC Number:

215-691-6

EC Name:

Aluminium oxide

Cas Number:

1344-28-1

Molecular formula:

Al2O3

IUPAC Name:

oxo[(oxoalumanyl)oxy]alumane

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)

Induction

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

33.3%

Day(s)/duration:

10 single injections (3 times weekly for 3 weeks)

Adequacy of induction:

other: Preliminary observations showed that one intradermal injection of 0.1 mL of a 33.3% aqueous suspension induced a mild skin reaction.

Challenge

No.:

#1

Route:

intradermal

Vehicle:

not specified

Concentration / amount:

33.3%

Day(s)/duration:

single injection

Adequacy of challenge:

other: Preliminary observations showed that one intradermal injection of 0.1 mL of a 33.3% aqueous suspension induced a mild skin reaction.

No. of animals per dose:

8

Details on study design:

RANGE FINDING TESTS: Preliminary observations showed that one intradermal injection of 0.1 mL of a 33.3% aqueous suspension induced a mild skin reaction.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 10 (test group), 1 (control group)
- Exposure period: 3 times weekly during 3 weeks
- Test groups: 0.05 mL of the 33.3% dilution at the first injection, 0.1 mL of the 33.3% dilution at all following injections (2 - 10)
- Control group: single injection of 0.05 mL of the 33.3% dilution
- Site: right flank
- Frequency of applications: 3 times weekly
- Duration: 3 weeks
- Concentrations: 33.3%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (test and control group)
- Day(s) of challenge: 2 weeks after the 10th injection of the induction phase
- Exposure period: single injection
- Test groups: 0.05 mL of the 33.3% dilution
- Control group: 0.05 mL of the 33.3% dilution
- Site: right flank
- Concentrations: 33.3%
- Evaluation (hr after challenge): 24

Positive control substance(s):

no

Results and discussion

Positive control results:

not applicable

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

33.3%

No. with + reactions:

8

Total no. in group:

8

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

33.3%

No. with + reactions:

8

Total no. in group:

8

Results 3

Reading:

1st reading

Group:

positive control

Dose level:

not examined

No. with + reactions:

0

Total no. in group:

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:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

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 8^th injection, an additional 2 animals showed moderate reactions after the 9^th injection and all 8 animals showed a moderate reaction after the 10^th 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 6^th injection when 5 animals showed a moderate reaction. All animals showed moderate reactions

after the 7^th to 10^th 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).