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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from 2005-07-18 to 2005-08-30
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 406)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
, EC Guideline B.6. (96/54/EC)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
old study - old standard for skin sensitisation testing

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: supplier: Charles River Deutschland GmbH
- Age at study initiation: 29 days
- Weight at study initiation: 266 - 306 g (positive reference group: 310 - 381 g)
- Housing: MAKROLON cages (type III plus), granulated textured wood (bedding material)
- Diet (e.g. ad libitum): ssniff Ms-H V2233 (ssniff Spezialitäten GmbH) ad libitum
- Water (e.g. ad libitum): tap water in drinking bottles (ad libitum)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C±3°C
- Humidity (%): 55 % ± 15 %
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light


IN-LIFE DATES: From: To: 2005-08-26

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: aqua ad iniectabilia
Concentration / amount:
test group:
- Stage 1 intracutaneous: 10 % (w/w) suspension of Antimony trioxide in aqua ad iniectabilia (induction)
- Stage 2 topical: 50 % (w/w) suspension of Antimony trioxide in aqua ad iniectabilia (induction)
- Stage 3 topical: 50 % (w/w) suspension of Antimony trioxide in aqua ad iniectabilia (challenge)
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: aqua ad iniectabilia
Concentration / amount:
test group:
- Stage 1 intracutaneous: 10 % (w/w) suspension of Antimony trioxide in aqua ad iniectabilia (induction)
- Stage 2 topical: 50 % (w/w) suspension of Antimony trioxide in aqua ad iniectabilia (induction)
- Stage 3 topical: 50 % (w/w) suspension of Antimony trioxide in aqua ad iniectabilia (challenge)
No. of animals per dose:
- in-test group: 20 animals
- vehicle control group (negative control): 10 animals
- positive control group: 20 animals (historical background, July 2005)
- preliminary study group: 8 animals
Details on study design:
RANGE FINDING TESTS:
PRELIMINARY STUDY
- 8 animals
- determination of intracutaneous administration: ∙ concentrations of 0.001, 0.01 and 0.1 % of test substrate (0.1 ml each) were injected into the
shoulder region of one test animal
∙ concentrations of 1, 5 and 10 % of test substrate were injected in a second animal

- determination of topical administration: ∙ 3 animals - each shaved or shaved and depilated
∙ 2 ml of test substance preparation was spread over a filter paper
∙ 2 concentrations each of 0.5, 1, 5, 10, 25 and 50 % of test substrate were applied
∙ occlusive dressing
∙ removal of filter papers after 24 or 48 h
∙ assessing sites for erythema and oedema (0 h, 24 h and, at depilated sites 48 h, after removal)

- results: no skin reactions were observed
--> the of 10 % antimony trioxide for intracutaneous, and 50 % for topical administration in the main study

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intracutaneous (stage 1) + topical (stage 2))
- Exposure period: 48 h (stage 2l)
- Test groups: ∙ 3 pairs of injections (0.1 ml each); 1) a 1:1 mixture (v/v) Freund's complete adjuvant (FCA) :0.9 % NACl
2) 10% suspension of antimony in water
3) a 1:1 mixture (v/v) of antimony suspension : FCA / 0.9 % NACl (= 10 % antimony)
∙ 1 sodium lauryl sulfate (10%, 0,5 ml) coating on same area 6 days after injection, as skin is not irritated from injection
∙ 1 topical exposure of 2 ml of a 50 % suspension of antimony on the same region 7 days after injection
- Control group: ∙ negative control: vehicle control group treated with aqua ad iniectabilia in the same way as test group
∙ positive control: treated with 2 % (w/v) benzocaine solution intracutaneous; 5 % (w/v) benzocaine solution topical
- Site: shoulder region (cleared of hair)



B. CHALLENGE EXPOSURE
- No. of exposures: 1 topical exposure (stage 3)
- Day(s) of challenge: 21 days after injection
- Exposure period: 24 h
- Test groups: ∙ L flank - 2 ml of a 50 % suspension of antimony; R flank - vehicle aqua ad iniectabilia
- Control group: ∙ negative control: vehicle control; L flank - 50 % suspension of antimony; R flank - vehicle aqua ad iniectabilia
∙ positive control: 5 % (w/v) benzocaine solution
- Site: flank region (cleared of hair)
- Concentrations: 2 ml of a 50 % (w/w) suspension in vehicle
- Evaluation (hr after challenge): 48 hr and 72 hr


OTHER:
Challenge controls:
no
Positive control substance(s):
yes
Remarks:
benzocaine

Results and discussion

Positive control results:
No positive control group was tested concurrently in this study. A positive historical background data group from a study performed July 2005 in the same laboratory.
- 11 cases of discrete or patchy erythema and 9 cases of confluent erythema in a 20 animals group

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle only (0 %)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. Dose level: vehicle only (0 %). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
vehicle only (0%)
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: negative control. Dose level: vehicle only (0%). No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test group
Dose level:
2 ml of a 50 % (w/w) suspension in vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. Dose level: 2 ml of a 50 % (w/w) suspension in vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
2 ml of a 50 % (w/w) suspension in vehicle
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 2 ml of a 50 % (w/w) suspension in vehicle. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
5% (w/v) benzocaine in 40 % ethanolic 0.9 % NaCl solution
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema (in 11 cases) and confluent erythema (in 9 cases)
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 5% (w/v) benzocaine in 40 % ethanolic 0.9 % NaCl solution. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema (in 11 cases) and confluent erythema (in 9 cases).
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
5 % (w/v) benzocaine in 40 % ethanolic 0.9 % NaCl solution
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
discrete or patchy erythema (in 11 cases) and confluent erythema (in 9 cases)
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 72.0. Group: positive control. Dose level: 5 % (w/v) benzocaine in 40 % ethanolic 0.9 % NaCl solution. No with. + reactions: 20.0. Total no. in groups: 20.0. Clinical observations: discrete or patchy erythema (in 11 cases) and confluent erythema (in 9 cases).

Any other information on results incl. tables

- no animal was found dead
- body weight gain of the animals treated with Antimony trioxide was within the range of the vehicle control group
- behavior of the animals treated with Antimony trioxide remained unchanged
- topical induction was not irritating to the non-depilated skin

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
This study shows that diantimony trioxide does not have sensitising properties.