Registration Dossier

Administrative data

Description of key information

Not a skin sensitiser (OECD406 GPMT, GLP, Key, rel.1)

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:
29 September 1998 - 30 October 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was performed according to OECD guideline 406 and under GLP conditions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
1996
Deviations:
no
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 (1998), the LLNA OECD test method was not adopted.
Species:
guinea pig
Strain:
other: Pirbright-White
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann
- Age at study initiation: No data
- Weight at study initiation: 330-398 g (mean: 359 g)
- Housing: In groups of 5 animals
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum, tap water in plastic bottles
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 5
- Humidity (%): 50 +/-20
- Air changes (per hr): Fully airconditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal
Vehicle:
water
Remarks:
deionized water
Concentration / amount:
0.2%
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Concentration / amount:
25%
Day(s)/duration:
Day 8 / 48 hours
Adequacy of induction:
other: maximum concentration tested / No signs of skin irritation observed in the sighting study
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Remarks:
deionized water
Concentration / amount:
25%
Day(s)/duration:
Day 22 / 24 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Control: 5
Treatment: 10
Details on study design:
RANGE FINDING TESTS:
1. Primary non-irritant concentration:
Prior to the determination of the primary non-irritation concentration in a dermal-occlusive test the animals received 4 intradermal injections of a 50% FCA emulsion (4x0.1 ml) into the dorsal area, since FCA may lower the threshold of primary irritation. Thereafter, each of the followig test concentrations was administered to the flanks of two guinea pigs: 25%, 5% and 1% in deionized water.
Hair of the flanks of the animals was removed mechanically. 0.5 ml of the test substance preparation was administered to a 2x2 cm cellulose patch, which was fixed to the flank and covered occlusively for 24 hours with a bandage and film. 24 hours after removal of the patches, the treated skin areas were examined for erythema and oedema.
2. To determine the tolerance of intradermal injections, each of the following preparations was administered twice by intradermal injection to 2 guinea pigs. The injection-sites were all within a dorsal area measuring 2x4 cm in the vicinity of the shoulders. 24, 48, 72 and 96 hours after administration the injection sites were examined for local tolerance.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal + epicutaneous)
- Exposure period:
Intradermal: Day 1
Epicutaneous: Day 8-10 (48 hours)
- Test groups: 1 (10 animals)
- Control group: 1 (5 animals)
- Site: Dorsal area of 2x4 cm
- Frequency of applications: Once (intradermal and epicutaneous)
- Concentrations:
Intradermal: 0.2%
Epicutaneous: 25%
Exposure according to guideline.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: Day 22
- Exposure period: 24 hours
- Test groups: 1 (10 animals)
- Control group: 1 (5 animals)
- Site: Left flank area of 5x5 cm (shaved)
- Concentrations: 25% in deionized water on a 2x2 cellulose patch
- Evaluation (hr after challenge): 24 and 48 hours after removal of patches erythema and oedema were evaluated.

OTHER:
- Body weight recorded at day 0 and 25 of study (beginning and end)
Challenge controls:
Not relevant
Positive control substance(s):
yes
Remarks:
Benzocain was tested in study no 98.0293 (ID induction: 1% benzocain in sesame oil DAB 10 ; dermal induction and challenge: 25% benzocain in sesame oil DAB 10)
Positive control results:
After the second challenge treatment four animals (40%) showed a positive reaction during the observation period.
The results obtained are typical for weak sensitizers.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
25% Aluminiumhydroxychlorid
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
deionized water
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No skin reactions
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
25% Aluminiumhydroxychlorid
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No skin reactions
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
deionized water
No. with + reactions:
0
Total no. in group:
5
Clinical observations:
No skin reactions
Remarks on result:
no indication of skin sensitisation
Reading:
rechallenge
Group:
positive control
Dose level:
25% benzocain in sesame oil DAB 10
No. with + reactions:
4
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation

Primary irritant concentration

No signs of irritation occurred after administration of the different test concentrations. Based on these results, a concentration of 25% test article in deionized water was chosen for the challenge at day 22.

Tolerance of intradermal injections

The intradermal injections with the 5.0% and 1.0% preparation caused moderate erythema and oedema. Additionally encrustions and indurations were observed. Intradermal injections with the 0.2% preparation caused moderate up to well-defined erythema and oedema. Additionally indurations were observed. Based on this preliminary test, a 0.2% preparation was selected for the intradermal injections in the main test.

Main test

Body weight gains of the animals were not impaired. The treated animals showed no clinical signs of intoxication throughout the study.

Intradermal injections with FCA (with and without test article) caused severe erythema and oedema as well as indurations and encrustations. The administration sites treated with the test substance in deionized water showed well-defined erythema and oedema as well as indurations. Intradermal injections of the vehicle alone exhibited no signs of irritation.

Epicutaneous induction showed severe erythema and oedema, indurated, and encrusted skin as well as necrosis and open wounds after removal of the patches at day 10 previously treated with FCA. The administration sites treated with the test substance showed well-defined erythema and oedema. The administration sites treated with the vehicle alone showed no signs of irritation.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this Guinea Pig Maximisation Test (OECD 406), Aluminiumhydroxychlorid did not induce any adverse skin reactions in the test group (sensitization rate: 0%). Therefore, the substance was not classified as a skin sensitizer 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, 10 guinea pigs were treated with Aluminiumhydroxychlorid, 5 animals were used as control group. Induction was done by intradermal (0.2%) and epicutaneous administration (50%), after that the animals were challenged by epicutaneous administration (50%). Body weights were measured before and after study.

None of the ten animals of the treatment group showed a positive skin reaction after 24 and 48 hours. No reactions were observed in the control group.

 

The results indicate a sensitization rate of 0% (0/10), which is below the threshold of 30%. Therefore, Aluminiumhydroxychlorid does not need to be classified as a sensitizing substance 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:

A key study was identified (Jensch, 1998). In this Magnusson & Kligman maximisation study (GPMT) performed according to OECD Guideline 406 and in compliance with GLP, 10 guinea pigs were treated with Aluminiumhydroxychlorid, 5 animals were used as control group. Induction was done by intradermal (0.2%) and epicutaneous administration (50%), after that the animals were challenged by epicutaneous administration (50%). Body weights were measured before and after study.

None of the ten animals (0%) of the treatment group showed a positive skin reaction after 24 and 48 hours. No reactions were observed in the negative control group.

Moreover, test substance did not induce skin sensitisation in a human repeated insult patch test study (Beller, 1957).

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.