Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 September 2000 and 21 October 2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study performed to GLP and guideline. Justification for read across: The chlorinated isocyanurates (sodium dichloroisocyanurate and sodium dichloroisocynaurate dihydrate) produce free available chlorine, in the form of hypochlorous acid (HOCl) as they dissolve in water. As the equilibria involve all of the possible chlorinated isocyanurates, the toxicity of sodium dichloroisocyanurate (NaDCC) and sodium dichloroisocyanurate dihydrate (NaDCC.2H2O) will be virtually equivalent at the same available chlorine concentration. The parent compound for all chlorinated isocyanurates is isocyanuric acid (cyanuric acid). All of the chlorinated isocyanurates are essentially equivalent, once they are dissolved in water at the low concentrations at which they are used. Therefore read across from sodium dichloroisocyanurate dihydrate to troclosene sodium is justified.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
GLP compliance:
yes (incl. certificate)
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ACL 56XG chlorinating composition
- Lot/batch No.: LI01-1005
- Storage condition of test material: room temperature in the dark over silica gel

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Burton-On-Trent, Staffordshire, UK
- Weight at study initiation: 257 to 359 g
- Housing: Solid floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 -23
- Humidity (%): 30 -70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 h light/12 h dark


Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal
Vehicle:
water
Concentration / amount:
Based on the results of sighting tests the concentrations of test material for the induction and challenge phases were selected as:

Intradermal induction: 0.1% w/w in distilled water
Topical induction: 1% w/w in distilled water
Topical challenge: 0.5% and 0.1% w/w in distilled water
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Based on the results of sighting tests the concentrations of test material for the induction and challenge phases were selected as:

Intradermal induction: 0.1% w/w in distilled water
Topical induction: 1% w/w in distilled water
Topical challenge: 0.5% and 0.1% w/w in distilled water
No. of animals per dose:
15 animals were used for the main study, ten test and five control
Details on study design:
The concentrations of test material to be used at each stage of the main study were determined by 'sighting tests' in which groups of guinea pigs were treated with various concentrations of test material.

Selection of concentration for intradermal induction:
Intradermal injections were made on the clipped shoulder of four guinea pigs (0.1%, 0.5%, 1% and 5% w/w in distilled water ). The degree of erythema was assessed at 24, 48, 72 hours and 7 days after injection. The highest concentration that caused only mild to moderate skin irritation was selected for intradermal induction for the main study.

Selection of concentration for topical induction:
2 guinea pigs (injected with Freunds Complete Adjuvent nine days earlier) were treated with four preparations of test material (75%, 50%, 25% and 10% w/w in distilled water). Due to severity of reactions two additional guinea pigs were treated with four lower concentrations (1%, 0.5% 0.1% and 0.05% in distilled water). The degree of erythema and oedema was evaluated at 1, 24 and 48 hours and the highest concentration producing mild to moderate dermal irritation was selected for topical induction stage of the main study.

Selection of concentration for topical challenge:
Four preparations of test material (1%, 0.5%, 0.1% and 0.05% w/w in distilled water) were applied to clipped flanks of two guinea pigs under occlusive dressing for 24 hours. The degree of erythema and oedema was evaluated at 1, 24 and 48 hours after dressing removal. The highest non-irritant concentration of test material and one lower concentration was selected fo the topical challenge stage of the main study.

Induction of test animals:
A row of three injections (0.1 ml each) were made on each side of the mid-line into a 20 mm x 40 mm area. The injections were:
a) Freunds Complete Adjuvant plus distilled water in the ratio 1:1
b) a 0.1% w/w formulation of the test material in distilled water
c) a 0.1% w/w formulation of test material in a 1:1 preparation of Freunds Complete Adjuvant plus distilled water

24 and 48 hours after intradermal injection the degree of erythema at the test material injection sites was evaluated.

On day 7 the same area used for the intradermal injections was treated with topical application of the test material formulation (1% w/w in distilled water). The occlusive dressing was kept in place for 48 hours. The degree of erythema and oedema was quantified one and twenty four hours following removal of the patches.

Induction of control animals:
Intradermal induction was performed using the same procedure as for the test animals except the test material was omitted. Injection b) was vehicle alone and injection c) was a 50% formulation of the vehicle in a 1:1 preparation of Freunds Complete Adjuvant plus distilled water. The topical induction was identical to that used for the test animals except the test material was omitted.

Challenge:
Shortly before treatment on day 21 an area of 50 mm x 70 mm on both flanks of each animal was clipped. The test material was applied at the maximum non-irritant concentration (0.5% w/w in distilled water) to the shorn right flank of the animal. To ensure that the maximum non-irritant concentration was used at challenge the test material at a concentration of 0.1% w/w in distilled water was similarly applied to a skin site on the left shorn flank. The patches were occluded. After 24 hours the dressing was removed. Approximately 24 and 48 hours after challenge dressing removal the degree of erythema and oedema was quantified.

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
0.1% and 0.5% w/w
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1% and 0.5% w/w. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1% and 0.5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1% and 0.5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
0.1% and 0.5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1% and 0.5%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1% and 0.5%
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.1% and 0.5%. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
Sodium dichloroisocyanurate dihydrate produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin under the conditions of the test.