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Description of key information

Strontium oxide cannot be tested in an in vitro or in vivo skin sensitisation assay, since it is classified as corrosive to the skin due to its strong acidic effect in water.

Supporting data with the non-corrosive strontium neodecanoate shows that the strontium cation (the species liberated by both substances upon dissolution) does not show skin irritating properties.

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:
supporting study
Study period:
2015-09-30 to 2015-11-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 1992-07-17
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
signed 2014-05-14
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at start of administration: 28 days
- Weight at start of administration: 314 - 342 g; positive control group: 323 – 350 g
- Housing: animals were kept in groups of 5 in MAKROLON cages (MZK 80/25); Granulated textured wood (Granulat A2, J. BRANDENBURG, 49424 Goldenstedt,
Germany) was used as bedding material in the cages.
- Diet (ad libitum): commercial diet, ssniff® Ms-H V2233 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: polyethylene glycol 400
Concentration / amount:
Intradermal induction: 0.01% suspension of the test item in the vehicle
Topical induction: 10% suspension of the test item in the vehicle
Challenge: 5% suspension of the test item in the vehicle
Route:
epicutaneous, occlusive
Vehicle:
other: polyethylene glycol 400
Concentration / amount:
Intradermal induction: 0.01% suspension of the test item in the vehicle
Topical induction: 10% suspension of the test item in the vehicle
Challenge: 5% suspension of the test item in the vehicle
No. of animals per dose:
10 male guinea pigs
Details on study design:
RANGE FINDING TESTS:
Eight animals were used for the preliminary test: 6 animals for the topical administration and 2 animals for the intracutaneous administration.
The allocation of different test sites of the animals was alternated in order to minimize site-to-site variations in response.
The shoulder and the flank region of the animals were shaved (approx. 5 cm x 5 cm). Animals, even if only slightly injured, were replaced.
(a) intracutaneous: 0.1 mL of the prepared test item was administered intracutaneously (shoulder region).
Six concentrations of strontium neodecanoate were tested by intracutaneous injection employing a 72-hour observation period: 0.01, 0.1, 0.5, 1, 5 or 10% suspensions in the vehicle. Three concentrations of the test item were injected intradermally into one, 3 further concentrations into a second animal.
(b) topical: six concentrations of strontium neodecanoate were tested by topical application to the shaved skin: 1, 5, 10, 25, 50 and 75% suspensions in the vehicle.
The test area of the animals each was shaved. 2 mL of the test preparation was spread over a filter paper (2 cm x 4 cm) and applied to the test area and held in contact by an occlusive dressing (Urgoplast®, FOURNIER Pharma GmbH, 66280 Sulzbach, Germany).
Two concentrations each were applied to the flanks of each animal.
The occlusive dressing and the filter paper containing the test item were removed after 24 or 48 hours from respective 3 animals and the application sites were assessed 24 and 48 hours (24-hour exposure) or immediately and 24 hours (48-hour exposure) after removal of the filter paper for erythema and oedema using the Magnusson and Kligman scale.

Results:
Intracutaneous injection:
The concentration of 0.01% revealed a moderate and confluent erythema 24 and 48 hours, a discrete or patchy erythema 72 hours after start of exposure. The concentrations of 0.1% and above revealed an intense erythema and swelling 24, 48 and 72 hours after start of exposure.
Topical application:
Concentrations of 1 or 5% did not reveal any skin reactions. A concentration of 10% revealed a discrete or patchy erythema 48 and 72 hours or 24 to 72 hours after start of 48- and 24-hour exposure, respectively. Concentrations of 25% and above revealed an intense erythema and swelling 48 and 72 hours or 24 to 72 hours after start of 48- and 24-hour exposure, respectively, and the test item adhered to the skin so the skin was torn off at patch removal.
Hence, it was decided to use a 0.01% suspension for the intracutaneous induction stage, a 10% suspension for the topical induction stage and a 5%
suspension for the challenge in the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal injection and dermal application)
- Site: shoulder region of the animals were shaved (approx. 5 cm x 5 cm).
- Frequency of applications: three pairs of intradermal injections were given once and 7 days later the same site was treated with a topical application. One day before the dermal application was applied the area was pretreated with 10% sodlium lauryl sulfate in vaseline in order to induce a local irritation, since 10% concentration of strontium neodecanoate in polyethylene glycol 400 was only slightly irritating in the 48-hour exposure to the skin of the test animals in the preliminary experiment.
- Exposure period: 48 hours (dermal application only)
- Concentrations:
Test animals:
Intradermal injections:
i) 0.1 mL FCA (diluted 1:1 with 0.9% NaCl)
ii) 0.1 mL test item in polyethylene glycol 400 (test item concentration: 0.01%)
iii) 0.1 mL test item in a 1+1 mixture (v/v) FCA/physiological saline (test item concentration: 0.01%)
Topical application:
10% test material

Control animals:
Intradermal injection:
i) 0.1 mL FCA (diluted 1:1 with 0.9% NaCl)
ii) 0.1 mL polyethylene glycol 400
iii) 0.1 mL polyethylene glycol 400 in a 1+1 mixture (v/v) FCA/physiological saline
Topical application:
polyethylene glycol 400

The skin reaction results of the intradermal induction exposure were evaluated at 24 and 48 hours, of the topical induction at 48 and 72 hours after start of exposure.
Evaluation of skin reactions according to the Magnusson and Kligman grading scale.

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (topical application two weeks after topical induction)
- Exposure period: 24 hours
- Site: flanks (right flank: polyethylene glycol 400; left flank: 5% of the test item)
- Evaluation (hr after challenge): 24 and 48 hours after patch removal
Evaluation of skin reactions according to the Magnusson and Kligman grading scale.

OBSERVATIONS:
- mortality: daily during the observation period
- clinical signs: daily during the observation period
- body weight: at start of study and at study termination
Challenge controls:
5 male guinea pigs were used as control group.
Challenge dose: 5% of the test item
Positive control substance(s):
yes
Remarks:
α-hexyl cinnamic aldehyde (85%) (vehicel: sesame oil; intracutaneous induction:10% v/v; topical induction: undiluted; challenge: 0.01%)
Positive control results:
Dunkin-Hartley guinea pigs treated with α-hexyl cinnamic aldehyde in sesame oil exhibited a sensitising reaction in all animals in form of a discrete or patchy erythema (grade 1) or a moderate and confluent erythema (grade 2) 48 and 72 hours after start of exposure.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
5% test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Body weight gain of the animals treated with strontium neodecanoate was within the range of the vehicle control during the experiment. Behaviour remained unchanged during the course of the study.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5% test item. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Body weight gain of the animals treated with strontium neodecanoate was within the range of the vehicle control during the experiment. Behaviour remained unchanged during the course of the study..
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
5% test item
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Body weight gain of the animals treated with strontium neodecanoate was within the range of the vehicle control during the experiment. Behaviour remained unchanged during the course of the study.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5% test item. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: Body weight gain of the animals treated with strontium neodecanoate was within the range of the vehicle control during the experiment. Behaviour remained unchanged during the course of the study..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5% test item
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 5% test item. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5% test item
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 5% test item. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
0.01% α-hexyl cinnamic aldehyde
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 0.01% α-hexyl cinnamic aldehyde. No with. + reactions: 20.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
0.01% α-hexyl cinnamic aldehyde
No. with + reactions:
20
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 0.01% α-hexyl cinnamic aldehyde. No with. + reactions: 20.0. Total no. in groups: 20.0.

MAIN STUDY:

1) Induction:

A 0.01% suspension of strontium neodecanoate in polyethylene glycol 400 chosen for the intracutaneous induction stage revealed a moderate and confluent erythema or discrete or patchy erythema 24 hours in all 10 test item-treated animals and a discrete or patchy erythema 48 hours after administration in 4 of the 10 test item- treated animals.

2 mL of a 10% suspension of strontium neodecanoate in polyethylene glycol 400/animal chosen for the topical induction stage were only slightly irritating to the shaved skin in the preliminary experiment. Hence, in the main study the skin was coated with sodium lauryl sulfate on the day before topical induction in order to induce a local irritation. This treatment resulted in a moderate and confluent erythema 48 hours and a discrete or patchy erythema 72 hours after start of exposure in all 15 animals (test and control animals).

2) Challenge:

The challenge with 2 mL of a 5% suspension of strontium neodecanoate in polyethylene glycol 400 /animal revealed no skin irritation in any animal and, thus, the test item had no sensitising properties.

The vehicle control revealed no skin reactions during the challenge.

OBSERVATIONS:

- body weight: body weight gain of the animals treated with strontium neodecanoate was within the range of the vehicle control during the experiment.

- clinical signs: behaviour remained unchanged during the course of the study.

Interpretation of results:
not sensitising
Conclusions:
Strontium neodecanoate was tested for its ability to produce skin sensitisation reactions in guinea pigs using the protocol according to the OECD TG 406.
A 0.01 % suspension of Strontium Neodecanoate in PEG 400 chosen for the 1 st (intracutaneous) induction stage revealed a moderate and confluent erythema or discrete or patchy erythema 24 hours in all 10 test-item treated animals and a discrete or patchy erythema 48 hours after administration in 4 of the 1 0 test item treated animals. 2 ml of a 10% suspension of Strontium Neodecanoate in PEG 400/animal chosen for the 2nd (topical) induction stage were only slightly irritating to the shaved skin in the preliminary experiment. Hence, in the main study the skin was coated with sodium lauryl sulfate on the day before stage 2 induction in order to induce a local irritation. This treatment resulted in a moderate and confluent erythema 48 hours and a discrete or patchy erythema 72 hours after start of exposure in all 15 animals. The challenge with 2 ml of a 5% suspension of Strontium Neodecanoate in PEG 400/animal revealed no skin irritation in any animal and, thus, the test item had no sensitising properties.
The vehicle control revealed no skin reactions during the challenge. Animals of the same strain treated with a-hexyl cinnamic aldehyde in sesame oil exhibited a sensitising reaction in all animals in form of a discrete or patchy erythema (grade 1) or a moderate and confluent erythema (grade 2) 48 and 72 hours after start of exposure.
Under the conditions of the test system, strontium neodecanoate was found to be not sensitising to guinea pigs.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Strontium oxide cannot be tested in an in vitro or in vivo skin sensitisation assay, since it is classified as corrosive to the skin due to its strong acidic effect in water. However, supporting data with the substance strontium neodecanoate shows that the strontium cation (the species liberated by both substances upon dissolution) does not show skin irritating properties:

A Guinea pig maximisation test according to OECD Guideline 406 conducted with strontium neodecanoate is considered to be reliable without restrictions. The results showed that the test item has no skin sensitisation potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Skin sensitisation

A skin sensitisation study cannot be performed with strontium oxide, since the substance is a strong base. Based on the information of a highly soluble non-corrosive strontium substance one may conclude that the assessment entity strontium does not have skin sensitising properties. An in vivo skin sensitisation study with strontium neodecanoate in Guinea pigs shows no skin sensitisation potential. Thus, strontium oxide does not require classification as skin sensitiser according to Regulation (EC) No 1272/2008 and subsequent regulations.