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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Guinea pig maximisation test (GPMT) (OECD 406)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 Sept 1989 - 13 Apr 1990
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
12.5.1981
GLP compliance:
not specified
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The GPMT study was conduct in 1990 prior recommendation to use LLNA

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Bor: DHPW
Sex:
not specified
Details on test animals and environmental conditions:
- Weight at study initiation: 431 g (test group); 454 g (controls)
- Housing: 1-5 animals in Macrolon cages type IV
- Diet (e.g. ad libitum): ad libitum, guinea pig complete diet G4
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 deg C
- Humidity (%): 60 +/- 5 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12TEST ANIMALS

Study design: in vivo (non-LLNA)

Induction
Route:
intradermal
Vehicle:
corn oil
Concentration / amount:
0.1ml 0.5 % test substance
Day(s)/duration:
7 days
Challenge
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Day(s)/duration:
2
No. of animals per dose:
20 (test item)
10 (control)
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 intradermal and topical
- Test groups: 1
- Control group: 1
- Site: Three pairs of intradermal injections of 0.1 ml volume are given in the shoulder region which is cleared of hair so that one of each pair lies on each side of the midline.
- Frequency of applications: once
- Duration: 7 days
- Concentrations:
Day 0: Intradermal application:
Test animals (20): 0.1 ml mixture (1:1) FCA and H2O ; 0.1 ml 0.5% test substance in corn oil ; 0.1 ml 0.5% test substance in FCA:H2O (1:1).
Control animals (10): 0.1 ml mixture (1:1) FCA and H2O ; 0.1 ml corn oil ; 0.1 ml FCA:H2O (1:1).
Day 7: Topical application:
Test group: A filter paper (2 x 4 cm) was fully-loaded with test substance applied to the test area and held in contact by an occlusive dressing for 48 hours.
Control animals: Corn oil was applied in the similair manner

B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 7 & 21
- Exposure period: 2 days
- Test groups: 1
- Control group: 1
- Concentrations: All animals: A patch loaded with the test substance is applied to one flank of the animals and a patch with the vehicle only was applied to the other flank. The patches are held in contact by an occlusive dressing for 48 hours (1st challenge) and 24 hours (2nd challenge)
- Evaluation (hr after challenge): 24h and 48h

OTHER: Approximately twenty-four hours before the topical induction application, the test area was treated with 10% SDS in vaseline, in order to create a local irritation.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
100 % test substance
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
100 % test substance
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Group:
positive control
Remarks on result:
not measured/tested

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Conclusions:
Tetrakis(2-ethylhexane-1,3-diolato)titanium demonstrated no sensitizing effect on the skin of female guinea pigs in the Magnusson-Kligman maximization test.
Executive summary:

Three pairs of intradermal injections of 0.1 ml were given in the shoulder region of animals (20 animals).

Injection 1: a 1:1 mixture (v/v) FCA/water

Injection 2: the 0.5% test substance in corn oil

Injection 3: the 0.5 % test substance in a 1:1 mixture (v/v) FCA/water

 

Control animals were treated with similar manner

Injection 1: a 1:1 mixture (v/v) FCA/water

Injection 2: corn oil

Injection 3: a 1:1 mixture (v/v) FCA/corn oil

 

At day 6 before the topical induction application, as the substance was not a skin irritant, the test area, after shaving was handled with 10% SDS in vaseline in order to create a local irritation. At day 7 a filter paper (2 x 4 cm) was fully-loaded with 100% test substance and applied to the test area and held in contact by an occlusive dressing for 48 hours. Control animals were exposed to corn oil in a similar manner. At day 21 second challenge was conducted. A patch loaded with the 100% test substance was applied to one flank of the animals. The patches were held in contact by an occlusive dressing for 24 hours. At 24 hours and 48 hours skin reactions were observed and recorded according to the Magnusson and Kligman grading scale.

At challenge no skin reactions were observed in any animals tested.