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Description of key information

To evaluate the irritation potential of the test article, skin or eyes of rabbits were treated with the test substance or a structural analogue and reactions were observed and scored up to 72h post-treatment. Application onto skin provoked slight erythema which resolved within 72h. In contact with eyes, slight reactions at conjunctiva and cornea were observed. All reactions were reversible within 72h and are below the threshold of significance. The test substance is considered to be as non-irritating to skin or eyes.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
other: The procedure adopted was the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).
Principles of method if other than guideline:
The procedure adopted was the patch-test technique described in the "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the US Association of Food and Drug Officials (AFDO).
GLP compliance:
not specified
Species:
rabbit
Strain:
other: English Silver strain
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: /
- Age at study initiation: /
- Weight at study initiation: 2-3 kg
- Housing: singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: /

ENVIRONMENTAL CONDITIONS
- Temperature (°C):/
- Humidity (%):/
- Air changes (per hr):/
- Photoperiod (hrs dark / hrs light):/

IN-LIFE DATES: From: To:/
Type of coverage:
occlusive
Preparation of test site:
other: shaved and left hand side abraded
Vehicle:
other: 50 % polyethylene glycol suspension
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): 50% solution

VEHICLE
- PEG 400
Duration of treatment / exposure:
24h
Observation period:
72h
Number of animals:
6 (3 per sex)
Details on study design:
TEST SITE
- Area of exposure: back and flanks
- % coverage: /
- Type of wrap if used: A gauze patch 2.5 x 2.5 cm was soaked with the test substance and immediately applied to the prepared skin. The patch was covered with a plastic film 5 x 5 cm, which was fixed to the body with adhesive tape.

REMOVAL OF TEST SUBSTANCE
- no washing

SCORING SYSTEM: Draize system
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 and 72h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 and 72h
Score:
0
Max. score:
4
Interpretation of results:
GHS criteria not met
Conclusions:
The substance is to be considered as non-irritant to the skin of rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
other: see below
Principles of method if other than guideline:
"Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.
GLP compliance:
not specified
Species:
rabbit
Strain:
other: English Silver strain
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: /
- Age at study initiation: /
- Weight at study initiation: /
- Housing: singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: /

ENVIRONMENTAL CONDITIONS
- Temperature (°C): /
- Humidity (%): /
- Air changes (per hr): /
- Photoperiod (hrs dark / hrs light): /

IN-LIFE DATES: From: To: /
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
30 sec until washing, 7 days without washing (observation period)
Observation period (in vivo):
7d
Number of animals or in vitro replicates:
3 per sex
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): 10 ml warm water
- Time after start of exposure: after 30 sec

SCORING SYSTEM: "Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics" (1959) of the AFDO.

TOOL USED TO ASSESS SCORE: hand-slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: all time points
Score:
0
Max. score:
80
Irritation parameter:
iris score
Basis:
mean
Time point:
other: all time points
Score:
0
Max. score:
10
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: all time points
Score:
0
Max. score:
20
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is to be considered as non irritant to the eye of rabbits.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Read across justification

The potential to cause irritation at skin or eyes was assessed at the test item itself and, additionally, at a structural analogue. Both substances share high similarity in structure; the test substance itself is a calcium salt whereas the analogue is barium salt. Moreover,both substances are minimal soluble in water. Therefore, it is acceptable to derive additional information on skin and eye irritation from the data of the analogue substance.

 

Procedure and observations

The skin and eye irritation potential of the test substance was evaluated in four studies. In addition, two studies from a structural analogue are also available.

In the course of the skin irritation study (Ciba, 1972), six (three per sex) English silver Strain rabbits were exposed for 24 hours to 0.5 g of the substance. Effects were scored 24 and 72 hours after removal of the wrap.The test article did not induce any effects on intact or abraded rabbit’s skin.

Another skin irritation study was performed similar to OECD guideline 404 (Synthesia 1993). Application of the substance onto skin did not provoke any effects and is therefore not considered to be irritating. However, analytical data and purity of the test material were not confirmed by the provider. Thus, this study is regarded as not reliable.

Read Across to CAS 5280-70-6

In this study (Ciba, 1980), primary skin irritation properties of the test material were investigated by topical application of 0.5 g of the test article in PEG onto shaved intact and abraded flank skin of each of three male and three female Californian rabbits. The scoring of skin reactions was performed 24 and 72 hours after removal of the dressing. Under the conditions of this experiment, the test substance induced slight erythema when applied onto abraded rabbit skin. All reactions resolved within 72h.

A study according to OECD 405 was performed to evaluate the eye irritation potential of the test article (Ciba, 1972b). Six English Silver Strain rabbits (three per sex) were exposed to 0.1 g of the test article. The treated eyes were rinsed at three of six animals 30 sec after application. Scoring of irritation effects was performed 1, 2, 3, 4 and 7 days after test article application. The test article did not cause any reaction to washed or unwashed eyes.

A supporting eye irritation test in rabbits was performed according OECD guideline 405 (Synthesia 1993). The test material was instilled into the conjunctival sac of a rabbit eye (three animals each). Effects on cornea, iris and conjunctiva were scored 1, 24, 48 and 72h after treatment. Swelling and redness were observed after 1h and 24h. All symptoms resolved within 72h. However, analytical data and purity of the test material were not confirmed by the provider. Thus, this study is regarded as not reliable.

Read Across to CAS 5280-70-6

The eye irritation potential of the analogue substance was investigated by instillation of 0.1 mg into one eye of each of three male and three female Californian rabbits (Ciba, 1980a). The treated eyes were rinsed at three of six animals 30 sec after application. Scoring of irritation effects was performed 1, 24, 48 and 72 hours after test article application. The substance induced slight reactions at conjunctiva (redness, chemosis and discharge) and cornea (opacity). All effects were reversible within 72h. Washed eyes tended to show a less severe reaction.

 

Discussion

Application of the test substance or the analogue onto skin induced slight erythema. Administration into the conjunctival sac of the rabbit eye induced slight redness and opacity. All reactions were reversible within 72h and are below the threshold of significance.

Therefore, the test substance is considered to be as non-irritating to skin or eyes.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified as irritating for skin or eyes under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for irritation under Regulation (EC) No. 1272/2008,

as amended for the second time in Directive (EC 286/2011).