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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:
14 Jun - 16 Jul 2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP - Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted Jul 1992
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): SAPO-11
- Physical state: powder
- Analytical purity: > 91.0%
- Lot/batch No.: MG31582-17CP
- Expiration date of the lot/batch: none, stable for an indefinite period
- Storage condition of test material: at room temperature

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, UK
- Age at study initiation: approximately 4 - 7 weeks
- Weight at study initiation: 303 - 380 g
- Housing: in groups of five in suspended metal cages with wire mesh floors. Animals were given autoclaved hay 3 times/wk at irreglular intervals and plastic tubular pipes were included in the cage.
- Diet: vitamin C-enriched guinea-pig diet (Harlan Teklad 9600 FD2 SQC), ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 50 ± 20
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Induction: 7.5% (intradermal) and 65% (epicutaneous)
Challenge: 65%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Induction: 7.5% (intradermal) and 65% (epicutaneous)
Challenge: 65%
No. of animals per dose:
10 (test group)
5 (control group)
Details on study design:
RANGE FINDING TESTS:
Prior to the start of the main study, the intradermal and topical irritancy of the test substance was investigated to select the minimum irritant test substance concentrations for the induction phase, and the maximum non-irritant concentration by the topical route and a dilution of this for the challenge phase of the main study.
The animals for the topical irritancy investigations were pre-treated with an intradermal injection of Freund's Complete Adjuvant, 50:50 with sterile water, approximately one week prior to the start of the preliminary investigations.
Procedure for intradermal injections: Intradermal injections (0.1 mL/site) were made into the clipped and shaved flank of two guinea pigs, using a range of concentrations (0.1 to 10% w/v) of SAPO-11 in water. The resulting dermal responses were assessed approximately 24 and 72 hours later.
Procedure for topical application: Patches of Whatman No. 3 paper (2 cm x 2 cm) were saturated (volume approximately 0.2 mL per patch) with a range of concentrations (20 to 65% w/v) of SAPO-11 in water and applied to the clipped and shaved flanks of each of four guinea pigs. The patches were covered by a strip of "Blenderm" and firmly secured by "Elastoplast" wound round the trunk and fixed with an impervious plastic adhesive tape. The dressings were removed after an exposure period of approximately 24 h and the reaction sites were assessed for erythema and edema. Further examination of the sites was carried out approximately 24 and 48 h after removal of the dressings.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: single injection (epidermal) and 48 h (epicutaneous)
- Test groups:
Intradermal, Day 1 (3 pairs of injections, 0.1 mL/site):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: test substance in water
Injection 3: test substance in a 1:1 mixture (v/v) FCA/water

On Day 7, the test sites were treated with 0.5 mL 10% sodium lauryl sulfate.

Epicutaneous, Day 8: test substance in water

- Control group:
Intradermal, day 1 (3 pairs of injections, 0.1 mL/site):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: water
Injection 3: water in a 1:1 mixture (v/v) FCA/water

On Day 7, the test sites were treated with 0.5 mL 10% sodium lauryl sulfate.

Epicutaneous, Day 8: water

- Site: shoulder region (intradermal and epicutaneous)
- Frequency of applications: once (intradermal on Day 1 and epicutaneous on Day 8)
- Duration: Day 1 - 10
- Concentrations: 7.5% (intradermal), 65% (epicutaneous)

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day(s) of challenge: 22
- Exposure period: 24 h
- Test groups: test substance
- Control group: water
- Site: left flank
- Concentrations: 32.5 and 65% (anterior and posterior of left flank)
- Evaluation (hr after challenge): 48 and 72 h (after application)

OTHER: The dermal reactions to the intradermal injections were recorded 24 h after the injections, and the dermal reactions to the topical induction were recorded folowing patch removal.
Positive control substance(s):
yes
Remarks:
hexyl cinnamic aldehyde

Results and discussion

Positive control results:
A reliability check is carried out at regular intervals with hexyl cinnamic aldehyde to check the sensitivity of the test system and the reliability of the experimental methods used by the test laboratory. In an independent study performed in 2001 (report No. HLS/132), hexyl cinnamic aldehyde induced sensitisation in 100% (10/10) of the Himalayan guinea pigs challenged with undiluted test substance, and a 50% solution. A 10% solution was used for intradermal induction and undiluted test substance was used for topical induction.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
challenge: 32.5 and 65%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: challenge: 32.5 and 65%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
challenge: 32.5 and 65%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: challenge: 32.5 and 65%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
challenge: 32.5 and 65%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: challenge: 32.5 and 65%. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
challenge: 32.5 and 65%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: challenge: 32.5 and 65%. No with. + reactions: 0.0. Total no. in groups: 10.0.

Any other information on results incl. tables

Necrosis was observed at all the injection sites where FCA was injected with water or with test substance, while there were no effects at injection sites of test substance and water alone. There were no dermal effects at the topical induction site in any animal. No dermal effects were recorded at the application site following the challenge treatment. There was no mortality and no adverse clinical signs were observed. No effects on body weight were noted.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified