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Administrative data

Description of key information

Calcium sulfate is not considered to be irritating to the 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
Study period:
Not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to internationally accepted testing guidelines.
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Not applicable
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Provided by Grabjas Jordi
- Age at study initiation: ~ 12 weeks
- Weight at study initiation: 2.5 - 2.7 kg
- Housing: The rabbits were accommodated individually in stainless steel cages. The cages were provided with a rack floor and placed on shelves
- Diet: Rabbit standard diet ad libitum
- Water: ad libitum
- Acclimation period:


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2ºC
- Humidity (%): 40 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h of light and 12 h of darkness every 24 h.


Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
no
Amount / concentration applied:
0.5 g, moistened with distilled water.
Duration of treatment / exposure:
4 h
Observation period:
The response in the application area was evaluated after 30 - 60 min and 24, 48 and 72 h approximately once the exposure period had finished.
Number of animals:
3 animals
Details on study design:
The animals were shaved 24 h before the application using an electric shaver. Fur was removed from the dorsal area and flanks from the pelvic waist to the scapular waist. Over the shaved and healthy skin of the right side, a square test area of approximately 6 cm2 was delimited.
The substance was applied using an only dose of 0.5 g moistened with distilled water. Each time the test substance was placed over the corresponding test area and covered with an hydrophillic gauze of 2.5 x 2.5 cm approximately. The semi-occlusive patches were attached to the animal body using surgical tape.
Finally a gauze band was wrapped around the trunk of the rabbit and it was stuck with hypoallergenic surgical tape to keep the bandage in place. The objective of this bandage was maximising the cutaneous absorption of the test substance.
After 4 h of exposure, the bandage and the patches were removed. The residual product was cleaned softly using cotton wet with distilled water.
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
30 min after the removal of the semi-occlusive patch, very light erythema (grade 1) was observed for the three animals. 24 h after the application, only 2 animals showed hardly visible erythema (grade 1). During the readings performed 48 and 72 h after the treatment, no dermal alterations were observed in rabbits, so that the study was considered finished after this reading.
The average of the erythema and edema assessments for the 3 animals after 24, 48 and 72 h was 0.2 and 0.0 respectively.
Other effects:
The behaviour and physical condition of the rabbits were normal during the whole study. There were no mortalities.

Table 1: Primary dermal irritation following application of 0.5 g of the test substance:

Animal No.

Reaction

30 – 60 min

24 h

48 h

72 h

970

Erythema

1

0

0

0

Edema

0

0

0

0

966

Erythema

1

1

0

0

Edema

0

0

0

0

987

Erythema

1

1

0

0

Edema

0

0

0

0

Interpretation of results:

The substance was classified according to the following scale, in accordance with Guideline 83/467/CEE, Annex VI, part IIB.

A substance or preparation is considered irritant if the inflammation of the skin with duration of at least 24 h corresponds to one of the following values:

- average value for the whole group of animals:

Erythemose lesions - 2 or higher

Edematose lesions - 2 or higher

- or lesions equivalent to the average values mentioned above, calculated for each animal, to 2 animals at least.

It is necessary to use the measure performed in every reading (24, 48, 72 h) of each type of lesion to calculate the respective average values. A substance is considered corrosive if it produces tissue destruction in the whole skin thickness, to at least 1 animal. It is considered to produce burns if tissue lesions in the whole skin thickness appear in an exposure period no longer than 4 h. If tissue lesions in the whole skin thickness appear in an exposure period no longer than 3 min, the product is considered to produce serious burns.

Interpretation of results:
GHS criteria not met
Conclusions:
Calcium sulfate is not irritating to skin.
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
Study period:
Not specified
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was performed according to internationally accepted testing guidelines.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: provided by Granjas Jordi.
- Age at study initiation: ~ 12 weeks
- Weight at study initiation: 2.2 - 2.7 kg
- Housing: The rabbits were accommodated individually in stainless steel cages with rack floors
- Diet: Rabbit standard diet ad libitum
- Water : Water available ad libitum



ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 ± 2ºC
- Humidity (%): 46 - 70 %
- Photoperiod (hrs dark / hrs light): 12 h of light and 12 h of dark every 24 h


Vehicle:
not specified
Controls:
other: One eye in each rabbit was treated, with the other eye remaining as a control.
Amount / concentration applied:
100 mg of anhydrite was applied to each animal.
Duration of treatment / exposure:
A single dose of anhydrite was applied to each animal. The animal was immobilised for the application and the product was placed in the conjunctival sac of the right eye, which was perfectly accessible by gently pulling the lower lid away from the eyeball.
Observation period (in vivo):
The behaviour of the animals was observed immediately after the product instillation and then they were returned to their cages. The grade of eye irritation was evaluated for every rabbit 1, 24, 48 and 72 h after the treatment.
After 24 h further corneal observations were performed by the instillation of a 2 % aqueous solution of fluorescein sodium, The aqueous solution was intilled on the test area, washing this with a physiological solution. Once the excess fluorescein was removed, the corneal alterations were observed with the aid of a transiluminator fitted with a cobalt blue filter.
Number of animals or in vitro replicates:
3
Details on study design:
The lids of the treated eye were then hed together for about 1 sec. The left eye was untreated and served as a control. Immediately after the product instillation, the rabbits were kept with a plastic collar for 1 h so that they could not rub their eyes.
In order to facillitate the evaluation of the eye alterations, the document "Illustrated Guide for Grading Eye Irritation by Hazardous Substances", was used, edited by Superintendent Documents, Government Printing Office, Washington D. C. USA.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
iris score
Basis:
mean
Remarks:
all animals
Time point:
24/48/72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
not fully reversible within: 72 hrs
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hrs
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 48 hrs
Irritant / corrosive response data:
The substance anhydrite induced, 1 h after the instillation, blood vessels of a diffused crimson colour (grade 2) in the conjunctivae, accompanied by obvious swelling with partial eversion fo the eyelids (grade 2) and slight lacrimation (grade 1). One rabbit also showed an area of diffuse opacity in the cornea. All the animals showed irridial lesions (grade 1).
24 h after the treatment, blood vessels of a diffused crimson colour (grade 2) in the conjunctivae were observed in one animal and blood vessels clearly hyperaemic (grade 1) were observed in the other two. Two rabbits showed slight eyelid swelling (grade 1). One rabbit also showed an area of opacity in the cornea (grade 1) that covered less than a quarter of it.
48 h after application, two animals showed hyperaemia (grade 1).
72 h after instillation, only one animal showed blood vessels slightly hyperaemic (grade 1) in the conjunctivae.
Other effects:
The behaviour and physical condition of the rabbits were normal during the whole study; there were no mortalities.

Table 1: Observations of ocular alterations after administration:

Animal No.

Region of the eye

1 h

24 h

48 h

72 h

951

Cornea

0

0

0

0

Iris

1

0

0

0

Conjunctiva: Hyperemia

2

1

1

1

Conjunctiva:Edema

2

0

0

0

973

Cornea

0

0

0

0

Iris

1

0

0

0

Conjunctiva: Hyperemia

2

1

0

0

Conjunctiva:Edema

2

1

0

0

593

Cornea

1

1

0

0

Iris

1

0

0

0

Conjunctiva: Hyperemia

2

2

1

0

Conjunctiva:Edema

2

1

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Calcium sulfate is not irritating to eyes
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In a reliable OECD guideline in vivo skin irritation study (Canut 1990) 0.5 g calcium sulfate anhydrite was applied to the shaved skin of 3 New Zealand White rabbits under a semiocclusive patch for 4 hours.Animals were observed after removal of the patch at 30 and 60 mins and 24, 48 and 72 h. The average of the erythema and edema assessments for the 3 animals after 72 h was 0.0. Calcium sulfate was found to be non-irritating to the skin in rabbits.

 

Eye irritation

In a reliable OECD guideline in vivo eye irritation study (Canut 1990) 100 mg calcium sulfate anhydrite was instilled into the eyes of 3 New Zealand White rabbits. Ocular observations were made at 1, 24, 48 and 72 h after instillation. Grade 1 and 2 conjunctival hyperaemia as well as grade 1 chemosis were observed 24h after application, which fully recovered within 72h in two of three animals. Taken together, calcium sulfate need not to be classified as irritating to the eyes.

Justification for classification or non-classification

In the in vivo skin and eye irritation studies calcium sulfate was non-irritant and required no classification under CLP.