Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18th April 2006 to 19 September 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Dikaliumheptafluorotantalat (Kaliumtantalfluorid)
- Substance type: White powder
- Storage condition of test material: At room temperature, tightly closed and dry.

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann, Gartenstrasse 27, D-33178 Borchen, Germany.
- Age at study initiation: Approximately 5-7 weeks at the first application
- Weight at study initiation: 295g to 407g at the first application.
- Housing: Grouped cages in plastic containers (46 cm x 105 cm x 36 cm)
- Diet: Altromin maintenance diet No. 3123 ad libitum.
- Water: Tap water ad libitum
- Acclimation period: Step 1 - 12 days; Step 2 - 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: Step 1 - 22.1ºC; Step 2 - 22.5ºC. (figures are averages).
- Humidity: Step 1 - 52.2%; Step 2 - 68.9% (figures are averages).
- Air changes (per hr): approximately 12 per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial light/12 hours darkness

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: Intradermal: physiological saline
Concentration / amount:
For epicutaneous exposure: 50 % (w/v) of test material to deionised water.
For intradermal exposure: 0.5 % (w/v) of test material to physiological saline.
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: Intradermal: physiological saline
Concentration / amount:
For epicutaneous exposure: 50 % (w/v) of test material to deionised water.
For intradermal exposure: 0.5 % (w/v) of test material to physiological saline.
No. of animals per dose:
10 females per dose for the test material and 5 females per control.
Details on study design:
MAIN STUDY
A. INDUCTION EXPOSURE
1st induction exposure: intradermal injection
- No. of exposures: 10 females.
- Two intradermal injections were made side by side at the following sites: cranial, middle and caudal.
- Volume administered in each case: 0.1 mL
- Concentrations: 0.5 % w/v of test material in physiological saline (step 1), 5% w/v of test material in physiological saline (step 2)
- FCA was used to enhance a possible sensitisation, and the test material was diluted with FCA.
- The sight was examined 24 hours after exposure.
- Control: 5 females were exposed in the same manner to physiological saline.

2nd induction exposure: epicutaneous exposure
- No. of exposures: The same 10 females were used as in the 1st induction.
- sight pretreated with n-dodecylsulfate, one day before exposure.
- Exposure was over a period of 48 hours with an occlusive dressing.
- Volume: either 0.5 mL of the test material or 0.5 mL of deionised water.
- Concentrations: 50 % (w/v) of test material in deionised water
- The sight was examined 24 hours after exposure.
- Control: The same 5 females were exposed in the same manner to deionised water.

B. CHALLENGE EXPOSURE
- No. of exposures: 10 females
- Day(s) of challenge: 24 hours with an occlusive dressing.
- Sight: left flank
- Volume: 0.5 mL of the test material and 0.5 mL of deionised water.
- Concentrations: Right flank was exposed to deionised water, the left flank was exposed to 50 % (w/v) of the test material in deionised water.
- Evaluation (hr after challenge): 21 hr after patch was removed the sight was cleaned, the approximately 3 hrs later the skin was examined.

All animals were observed daily for behavioural changes or signs of toxicity.

A supporting table (table 1) can be seen in the field "Any other information on materials and methods incl. tables".
Challenge controls:
5 females.
The right flank was exposed to deionised water.
The left flank was exposed to 50 % (w/v) of the test material in deionised water.
Positive control substance(s):
yes
Remarks:
hexyl cinnamic aldehyde

Study design: in vivo (LLNA)

Vehicle:
other:
Statistics:
The t-test was used to evaluate differences of the mean body weights between the test substance group and the control group on days 0 and 24.

Results and discussion

Positive control results:
10 females were exposed for the positive substance control and 5 females were exposed for the negative control group. 9/10 animals had a positive response to this test.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
other: 1st and 2nd
Hours after challenge:
48
Group:
test group
Dose level:
0.5% (w/v)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: other: 1st and 2nd. . Hours after challenge: 48.0. Group: test group. Dose level: 0.5% (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
other: 1st and 2nd
Hours after challenge:
48
Group:
test group
Dose level:
50% (w/v)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: other: 1st and 2nd. . Hours after challenge: 48.0. Group: test group. Dose level: 50% (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
other: 1st and 2nd
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: other: 1st and 2nd. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
other: 1st and 2nd
Hours after challenge:
48
Group:
negative control
Dose level:
50% (w/v)
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: other: 1st and 2nd. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% (w/v). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Any other information on results incl. tables

Table 2. Scheme for scoring the skin

Skin reaction Score Graded as 
no reaction 0 normal
very slight erythema 1 mild
well defined erythema 2 moderate
severe erythema and/or oedema 3 severe

Table 3. Results of skin examination

    Skin reaction after induction After challenge* Skin reaction positive (yes/no)
Step No. Animal No. intradermal** epicutaneous 24 hrs 48 hrs
1 61 2/2 3 0/0 0/0 no
  62 2/2 3 0/0 0/0 no
  63 2/2 3 0/0 0/0 no
  64 3/3 3 0/0 0/0 no
  65 3/3 3 0/0 0/0 no
  66 2/2 3 0/0 0/0 no
  67 2/1 3 0/0 0/0 no
  68 3/1 3 0/0 0/0 no
  69 3/3 3 0/0 0/0 no
  70 3/1 3 0/0 0/0 no
2 91 3/3 3 0/0 0/0 no
  92 3/3 3 0/0 0/0 no
  93 3/3 3 0/0 0/0 no
  94 3/3 3 0/0 0/0 no
  95 3/3 3 0/0 0/0 no
  96 1/3 3 0/0 0/0 no
  97 3/3 3 0/0 0/0 no
  98 3/3 3 0/0 0/0 no
  99 3/3 3 0/0 0/0 no
  100 3/3 3 0/0 0/0 no

*skin reactions were attributed to the adjuvant

**scores for left/right injection site

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, after the challenge exposures, no animal of the test material groups had a positive reaction at the test material treated sites 24 hours and/or 48 hours after the end of the exposure. No adverse skin reactions were observed in the control animals. Therefore no animal of the test material group was regarded as sensitised.
Executive summary:

The skin sensitisation potential of the test material was determined in a GLP-compliant guinea pig maximisation testing performed in accordance with standardised guidelines OECD 406 and EU Method B.6. The test material was applied as:

0.5% w/v in physiological saline for the intradermal induction (step 1)

5% w/v in physiological saline for the intradermal induction (step 2)

50% w/v in deionised water for the epicutaneous induction (each step) and

50% w/v in deionised water for the challenge exposure (each step).

No adverse clinical or behavioural signs were observed. No statistically significant differences were seen in mean body weights. Observations showed no adverse skin reactions in the control or animals exposed to the test material. Therefore, under the conditions of the study the test material was determined not to be a skin sensitiser.