Antimony sulphide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across based on grouping of substances (category approach)

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)

Justification for type of information:

Upon dissolution in aqueous media at physiologically relevant concentrations and pH conditions, the only aqueous antimony species emerging from all considered trivalent antimony substances is the trivalent antimony cation. In vitro bioaccessibility testing in various artificial body fluids (Hedberg et al., 2010) has shown that diantimony trisulfide compared to diantimony trioxide has a similar release rate of antimony ions.
Thus, with respect to systemic toxicity, read-across from diantimony trioxide toward diantimony trisulfide is justified

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

, EC Guideline B.6. (96/54/EC)

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

old study - old standard for skin sensitisation testing

Test material

Test material information

Constituent 1

Reference substance name:

Diantimony trioxide

EC Number:

215-175-0

EC Name:

Diantimony trioxide

Cas Number:

1309-64-4

Molecular formula:

Sb2O3

IUPAC Name:

dioxodistiboxane

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)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: aqua ad iniectabilia

Induction 2

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)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: aqua ad iniectabilia

Challenge 2

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)

Results

Results 1

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.

Results 2

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.

Results 3

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

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.

Results 4

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

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.

Results 5

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).

Results 6

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.