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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:
3 January 1986 - 8 February 1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study was conducted according to OECD guideline 406 and under GLP conditions

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:
criteria for classification of sensitizing potential is used (see materials&methods). No data on control positive.
Principles of method if other than guideline:
At the time of study completion (1986), the LLNA OECD test method was not adopted.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
At the time of study completion (1986), the LLNA OECD test method was not adopted.

Test material

Constituent 1
Test material form:
solid: particulate/powder
Details on test material:
- Name of test material (as cited in study report): Chlorhydrol ultrafine
- Physical state: Solid (white powder)
- 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: 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 (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum, tap water
- Acclimation period: Min. 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
Vehicle:
water
Remarks:
distilled water
Concentration / amount:
0.1% w/w
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
distilled water
Concentration / amount:
50% w/w
Day(s)/duration:
Day 8 / 48 hours
Adequacy of induction:
other: highest level which did not produce excessive inflammation
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
- Concentrations:

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.
Challenge controls:
No data.
Positive control substance(s):
not specified

Results and discussion

Positive control results:
No data.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
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:
no indication of skin sensitisation
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:
no indication of skin sensitisation
Key result
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:
no indication of skin sensitisation
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:
no indication of skin sensitisation
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:
GHS criteria not met
Conclusions:
Under the conditions of this Guinea Pig Maximisation Test (OECD 406), Chlorhydrol Ultrafine did not induce any adverse skin reactions in the test group (sensitization rate: 0%). Therefore, the substance is not classified as a sensitiser according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In a Magnusson & Kligman maximisation study (GPMT) performed according to OECD Guideline 406 and in compliance with GLP, 20 female Dunkin-Hartley guinea pigs were exposed once intradermally (0.1%) and 2 times epicutaneously (50%) to the test article. Ten control animals were only exposed once epicutaneously (50%) during challenge. Positive skin reactions were evaluated according to a grading scale, and were used to calculate the sensitization rate. Body weights were measured before and after study.

No mortality was observed during the test. No skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48 h observations. Chlorhydrol Ultrafine produced a 0 % (0/20) sensitisation rate and was considered to be a non-sensitiser to guinea pig skin. Body weight gain was comparable between the test and control group.

Under the conditions of this Guinea Pig Maximisation Test (OECD 406), Chlorhydrol Ultrafine did not induce any adverse skin reactions in the test group (sensitization rate: 0%). Therefore, the substance is not classified as a sensitiser according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.