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Description of key information

Magnusson and Kligman test (OECD 406 test guideline, GLP, Kl. 2):  Chlorhydrol Ultrafine was tested in Guinea pig, 0% skin sensitisation rate.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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 with some deviations and under GLP conditions.
Qualifier:
according to
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:
Not applicable.
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.
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 hrs dark/12 hrs light.
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.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
distilled water
Concentration / amount:
50% w/w
Day(s)/duration:
Day 22 / 24 hours
Adequacy of challenge:
highest non-irritant concentration
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 criteria:
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
Positive control results:
No data.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
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
Key result
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 group
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
Key result
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
Key result
Reading:
other: Positive control
Group:
positive control
Remarks on result:
not measured/tested

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.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Literature search performed from 2010 to 2014 identified two sensitisation studies conducted in human with Aluminium chloride heaxhydrate and Aluminium chloride, respectively (Siemund et al., 2012; Schered et al., 2010). None of them was considered as reliable to assess the senitisation potential.

A key study was identified (Jones, 1986, Kr. 2). The study was conducted according to the OECD guideline No 406 and in compliance with GLP. In this study, 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 skin reactions were noted at the challenge sites of the test or control group animals at the 24 or 48 h observations. No effects were observed on body weight. Chlorhydrol Ultrafine produced a 0 % (0/20) sensitisation rate and was considered to be a non-sensitiser to guinea pig skin.

 

References:

- Siemund, Ingrid; Zimerson, Erik; Hindsen, Monica; Bruze, Magnus. Establishing aluminium contact allergy. Contact Dermatitis (2012), 67(3), 162-170.

- Scherer, K. 1 ; Simon, D. 2 ; Ballmer-Weber, B. 3 ; Pelloni, F. 4 ; Plaza, T. 5 ; Von Schulthess, A. 4 ; Kohler, E. 4 ; Drzimalla, K. 4 ; Bircher, A.J. (2010) Prevalence of contact sensitization to metals - First results of the scdrg study. Contact Dermatitis, suppl. SUPPL. 163: 95.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

- Skin sensitisation: based on the available data, no additional self-classification is proposed according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

- Respiratory sensitisation: No data was available for respiratory sensitisation. However, this substance is not a skin sensitizer, therefore according to Figure R.7.3 -2 of the Chapter R.7 (V 4.1 - October 2015) the chemical is not considered as a respiratory sensitizer.