Registration Dossier

Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

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:
other: Guideline study but GLP status unclear

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Magnusson and Kilgmann method.
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
There were no clinical signs of toxicity observed in any animal in either the test or control groups throughout the course of the study. In addition to this, all animals showed an increase in body weight on completion of the study.

Test material

Constituent 1
Chemical structure
Reference substance name:
Dialuminium titanium pentaoxide
EC Number:
234-456-9
EC Name:
Dialuminium titanium pentaoxide
Cas Number:
12004-39-6
Molecular formula:
Al2O5Ti
IUPAC Name:
Dialuminum titanium pentaoxide
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Aluminium titanium oxide.
- Molecular formula (if other than submission substance): Al2TiO5
- Molecular weight (if other than submission substance): 181.83
- Physical state: White powder

In vivo test system

Test animals

Species:
guinea pig
Strain:
Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Japan SLC, Co., Ltd.
- Age at study initiation: 9 weeks old.
- Weight at study initiation: 371.4 - 478.2 g
- Housing: The animals were housed in groups of five in suspended aluminium cages with stainless steel wire-mesh front and floor (W450 x D550 x H350mm). Cages were replaced once every week with washed and sterilized cages.
- Diet (e.g. ad libitum): Labo G Standard, Nosan Corporation, Japan provided ad libitum throughout the study.
- Water (e.g. ad libitum): Filtered tap water available ad libitum throughout the study.
- Acclimation period: 42 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): More than 10 fresh air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark.

IN-LIFE DATES: From: June 27th 2007 To: 24th August 2007.

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Intradermal induction - Preliminary study: 5%, 2%, 1%, 0.5%, 0.2% and 0.1%.
Cutaneous application - Preliminary study: 25, 10 and 1%

Main study:
Induction: 5%
2nd Induction: 25%
Challenge: 25%.
No. of animals per dose:
Test groups: 10 animals per group.
Control group: 5 animals per group.
Details on study design:
RANGE FINDING TESTS:
A preliminary study was conducted to select the appropriate concentrations for induction and challenge. Two animals were intradermally treated with the test substance at 5%, 2%, 1%, 0.5%, 0.2% and 0.1% in water for injection and water for injection (0%) as a control. 0.1 mL was applied per site, with 7 doses per body. Observations were recorded 24 and 48 hours after injection, with no skin reactions recorded at any of the application sites.

Lint patches (2 cmx 2cm) saturated with 0.2 mL of the test substance at 25%, 10% and 1% in water were applied to 2 animals. Three doses were applied to each animal. Observations were recorded 24 and 48 hours after application, with no skin reactions recorded at any of the application sites.

The concentrations chosen for the main study were determined to be 5% for the 1st induction, 25% for the 2nd induction and 25% for the challenge application.

MAIN STUDY
A. INDUCTION EXPOSURE
The test animals received three intradermal injections of a 1:1 water in oil emulsion mixture of FCA and distilled water, 5% test substance suspension in water for injection and a 1:1 water in oil emulsion mixture of FCA and 10% test substance suspension in water for injection. 0.1mL was applied per site.
After 7 days, a lint patch, saturated with 0.4 mL of 25% test substance suspension in water for injection was applied and held in place for 48 hours. The day prior to the 2nd induction, 0.5ml of 10% sodium dodecyl sulfate in petrolactum was painted to the scapular area in order to cerate local irritation.

B. CHALLENGE EXPOSURE
Two weeks after the 2nd induction, a 2cm x 2cm lint patch saturated with 0.2mL of 25% test substance suspension in water was applied to the right flank of each guinea pig and the site was occluded for 24 hours. After this time, the patch was removed and the treated area was wiped with absorbent cotton dipped in tap water to remove residual test material.

The application sites were assessed for erythema and swelling 24 and 48 hours after removal of the patches and the applicaiton sites were scored as follows:

Grade Criteria:
0 No reaction
1 Slight reaction (edges of area not defined)
2 Moderate reaction (area well-defined)
3 Severe reaction.

OTHER:
All animals were observed daily for clinical signs of toxicity during the experimental period. The body weights of the animals were measured on the day of the first induction and on the challenge day.
Challenge controls:
5 animals per group were in the challenge control. These animals were treated with water instead of the substance during the induction phase.
Positive control substance(s):
not specified

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No test animals showed any signs of erythema or swelling 24 hours after challenge exposure.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No test animals showed signs of erythem or swelling 48 hours after challenge exposure.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No signs of erythema or swelling in the control animals 24 hours after exposure to the challenge application.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
25%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No signs of erythema or swelling in the control animals 48 hours after exposure to the challenge application.
Reading:
other: Indication of no positive control group
Hours after challenge:
24
Group:
positive control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Clinical observations:
No Positive Control group was performed

Any other information on results incl. tables

There were no clinical signs of toxicity observed in any animal in either the test or control groups throughout the course of the study. In addition to this, all animals showed an increase in body weight on completion of the study.

Table 1: Results of the skin sensitization test of Aluminium magnesium titanium oxide:

Group

Aluminium magnesium titanium oxide - sensitized group

Aluminium magnesium titanium oxide - control group

Test substance used for induction treatment

Aluminium magnesium titanium oxide

Not applicable

Test substance used for challenge treatment

Aluminium magnesium titanium oxide

Aluminium magnesium titanium oxide

Induction:

1stinduction (intradermal)

2ndinduction (epidermal)

 

5%

25%

 

-

-

Number of animals used

10

5

Challenge

Skin reaction

Number of animals used

24 hrs

48hrs

24hrs

48hrs

E

S

E

S

E

S

E

S

25%

0

10

10

10

10

5

5

5

5

1

0

0

0

0

0

0

0

0

2

0

0

0

0

0

0

0

0

3

0

0

0

0

0

0

0

0

E=erythema

S=swelling

0=No reaction

1=Slight

2=Moderate

3=Severe.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
not sensitising
Conclusions:
No evidence of skin senisitisation was seen under the conditions of this study.
Executive summary:

The potential of aluminium magnesium titanium oxide to act as a skin sensitiser was determined in a study conducted in accordance with the Magnusson and Kligmann method. Female guinea pigs were sensitised with 5% test substance in the 1st induction, 25%

suspension in water in the 2nd induction and were then exposed to a challenge 2 weeks after the 2nd induction, in which a 25%

suspension in water was applied for a 24 hour exposure period. Skin reactions were made 24 and 48 hours after the challenge period.

No positive skin reactions were recorded in any test animal 24 or 48 hours after the challenge exposure.

Under the conditions of the study, aluminium magnesium titanium oxide is not classified as a skin sensitizer and does not require classification according to Regulation (EC) No. 1272/2008.