Strontium nitrate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-05-18 to 2010-06-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study reliable without restrictions

Justification for type of information:

Prior to the start of this in vivo eye irritation study, a weight of evidence analysis was performed in the interest of animal welfare and to minimize any testing likely to produce severe responses in animals. All available information was evaluated to determine the need for in vivo eye testing. An in vitro study was considered, but a negative result was anticipated, which should be confirmed in an in vivo study. Based on the available information, it was concluded that there was a need to perform this in vivo eye irritation study in rabbit in order to establish the possible eye irritating properties of the test substance.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

, 2002-04-24

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Strontium nitrate

EC Number:

233-131-9

EC Name:

Strontium nitrate

Cas Number:

10042-76-9

Molecular formula:

Sr(NO3)2

IUPAC Name:

strontium nitrate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Strontium nitrate
- Molecular formula: Sr(NO3)2
- Molecular weight: 211.63
- Physical state: White crystals
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperature in the dark
- pH (1% in water, indicative range): 6.4 - 7.0 (determined at NOTOX)
No further information on the test material was stated.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan, Belton, Leics, England
- Age at study initiation: At least 6 weeks old
- Weight at study initiation: At least 1 kg
- Housing: Animals were individually housed in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet: Pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy) approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21.0 ± 3.0ºC (actual range: 18.8 – 23.4ºC)
- Relative humidity: 40-70% (actual range: 38 - 81%)
- Air changes: Approximately 15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12/12
No further information on the test animals was stated

Test system

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Animals were treated by instillation of, on average, 99.2 mg (range 98.9 - 99.6 mg) of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance. The other eye remained untreated and served as the reference control.
No further information on the amount/concentration applied was stated.

Duration of treatment / exposure:

No data

Observation period (in vivo):

Approx. 1, 24, 48 and 72 hours and 7 days (all animals) and 14 and 21 days (two animals) after instillation of the test substance.

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

The study was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 9 days later, after considering the degree of eye irritation observed in the first animal.

SCORING SYSTEM: Draize scoring system. Other (local) effects were also recorded

TOOL USED TO ASSESS SCORE: Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. This procedure was repeated to assess
recovery.
Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp. In cases of equivocal results when comparing the treated and untreated eyes, the illustrated guide from the Consumer Product Safety Commission, Washington, D.C. 20207 was used for additional control purposes.

OBSERVATIONS:
Mortality/Viability: Twice daily
Toxicity: At least once daily
Body weight: Day treatment (prior to instillation) and after the final observation
Necropsy: Not performed
No further information on the study design was stated.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 10

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

The corneal injury consisted of slight dulling of the normal luster of the cornea, opacity (maximum grade 1) and/or epithelial damage (maximum 10% of the corneal area). The corneal injury fully resolved within 24 hours in one animal and within 48 hours in the other two animals.
Iridial irritation grade 1 was observed and resolved within 24 hours in all animals.
There was no evidence of ocular corrosion.
The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in one animal. Although chemosis and discharge resolved within 7 days in the other two animals, redness did not recover within 21 days in these animals. In addition, these two animals showed yellowish particulate matter embedded in the nictating membrane from 48 hours after instillation onwards.

Other effects:

No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye)

Conclusions:

According to the Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures, strontium nitrate should be classified as Irreversible effects on the eye (Category 1) and labeled as H318: Causes serious eye damage.
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as eye irritant and labeled as risk of serious damage to eyes.