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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
3 Jan - 8 Feb 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study tested with the source substance CAS 1327-41-9. According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
Scale for classification of sensitizing potential is used (see materials&methods)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
As no studies investigating the skin sensitisation of reaction mass of aluminium hydroxide and aluminium nitrate and aluminium sulphate are available in accordance to Regulation (EC) No. 1907/2006 Annex XI, 1.5 a read-across from supporting substances (structural analogues) e.g. aluminium compounds was considered. This study is not LLNA but LLNA studies available for other supporting substances. Moreover, LLNA is not always the most adequate approved method to assess Skin Sensitization. Additionally LLNA is in-vivo method and nowadays in vivo methods must not be performed without approval, preferably in-vitro methods are recommended.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Chlorhydrol Ultrafine
- Physical state: solid (white powder)
- Lot/batch No.: confidential information
- Storage condition of test material: 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: David Hall Limited, Burton-on-Trent, Staffordshire, UK
- Age at study initiation: 7-11 weeks
- Weight at study initiation: 334-411 g
- Housing: in groups of up to 4 animals
- Diet : ad libitum
- Water: tap water, ad libitum
- Acclimation period: approximately 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 45-65
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12-12

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: distilled water
Concentration / amount:
Intradermal induction: 0.1% w/w
Topical induction: 50% w/w
Topical challenge: 50% w/w
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: distilled water
Concentration / amount:
Intradermal induction: 0.1% w/w
Topical induction: 50% w/w
Topical challenge: 50% w/w
No. of animals per dose:
Treatment group: 20
Control group: 10
Details on study design:
RANGE FINDING TESTS:
Dose levels for each of the three stages of the main study were determined. Groups of two or more guinea pigs were used and up to two dose levels were tested on each group of animals.
Intradermal injection: Dilutions of test material in distilled water were tested to determine the highest level, up to 5% (w/v), that could be well tolerated both locally and systemically.
Topical application: Dilutions of the test material in distilled water were tested to determine the highest level which did not produce excessive inflammation and irritation in animals injected with FCA at least seven days previously.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous)
- Exposure period: 48 hours (epicutaneous)
- Test groups: 1 (20 animals)
- Control group: 1 (10 animals)
- Site: Shoulder region (40x60 mm)
- Frequency of applications: once


Treatment group:
- Intradermal (row of 3x0.1 ml injections on each side of the midline):
1. FCA plus distilled water in the ratio 1:1
2. A 0.1% (w/v) dilution of test material in distilled water
3. A 0.1% (w/v) dilution of test material in a 1:1 prepartion of FCA plus distilled water
- Epicutaneous:
Topical occlusive application of 0.2-0.3 mL test material (50% w/w in distilled water) on filter paper

Control group:
- Intradermal (row of 3x0.1 mL injections on each side of the midline):
1. FCA plus distilled water in the ratio 1:1
2. Distilled water
3. FCA plus distilled water in the ratio 1:1
- Epicutaneous:
Topical occlusive application of 0.2-0.3 mL distilled water on filter paper

B. CHALLENGE EXPOSURE
- No. of exposures:
- Day(s) of challenge:
- Exposure period: 24 hours
- Test groups: 1 (20 animals)
- Control group: 1 (10 animals)
- Site: 50-70 x 50 mm area on both flanks
- Concentrations: 50% in distilled water
- Evaluation (hr after challenge): 24 and 48 hours after removal of dressing. Four-point scale was used to record erythematous reactions:
0 - no reaction
1 - scattered mild redness
2 - moderate and diffuse redness
3 - intense redness and swelling

Number of positive responses was recorded, the sensitization response was calculated (% positive reactions) and this was compared with the following scale:
0% - non-sensitizer
1-28% - mild sensitizer
29-65% - moderate sensitizer
66-100% - strong sensitizer

OTHER:
Body weights measured at start and end of study.
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% Chlorhydrol Ultrafine
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No adverse skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% Chlorhydrol Ultrafine. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No adverse skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50% Chlorhydrol Ultrafine
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No adverse skin reactions
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% Chlorhydrol Ultrafine. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No adverse skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50% Chlorhydrol Ultrafine
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No adverse skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50% Chlorhydrol Ultrafine. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No adverse skin reactions.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50% Chlorhydrol Ultrafine
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No advese skin reactions
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% Chlorhydrol Ultrafine. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No advese skin reactions.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Remarks on result:
not measured/tested
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

Bodyweight gains of guinea pigs in the test group betwee day 0 and day 24 were comparable to those in the control group over the same period.

Applicant's summary and conclusion

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

A Guinea Pig Maximisation Test of Skin Sensitization was performed with the test substance according to OECD guideline 406 (Jones, 1986) and GLP. 20 female guinea pigs were treated with test substance and compared to 10 negative control animals. A 0.1% dilution of the test substance in water was used for intradermal induction symmetrically in two rows on each side of the spine and 50% used for epidermal induction on the shoulder region of test animals. All animals were challenged for 24 hours epicutaneously on the flank region with the 50% test. 24 and 48 hours after removal of the dressing, no positive skin were observed. Based on the study results no classification is required according to EU classification criteria for skin sensitisation.