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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 January 2013 - 12 February 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study in accordance with OECD Guidelines for Testing of Chemicals, Section 4, Health Effects, No.405, (EC) No 440/2008 Part B5; EPAOPPTS 870.2400.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report Date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Barium nitrate
- Substance type: White crystals
- Physical state: Solid
- Analytical purity: 99.52
- Lot/batch No.: 120724
- Expiration date of the lot/batch: 2013-09-13
- Storage condition of test material: Room temperature in the dark.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: At least 8 weeks.
- Weight at study initiation: At least 1.0 kg.
- Housing: 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 (e.g. ad libitum):Approximately 100 grams/day of pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy).
- Water (e.g. ad libitum): Ad libitum tap water.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): Aproximately 15
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

IN-LIFE DATES: From: 21 January 2013 To: 12 February 2013

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: One eye of each animal was left untreated as a reference control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):62.6 mg (range 62.2 – 63.0 mg). Equivalent to approximately 0.1 mL.

Duration of treatment / exposure:
24 hrs.
Observation period (in vivo):
14 days
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): None. 2% fluorecein stain was instilled to determine corneal damage.
- Time after start of exposure: 24 hr

SCORING SYSTEM: 1-4 for corneal irritation, iris, conjunctival irritation, chemosis, and discharge.

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24 hr
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hr
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hr
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
2
Reversibility:
fully reversible within: 72 hr
Irritant / corrosive response data:
Instillation of approximately 63 mg of barium nitrate (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in effects on the iris and conjunctivae. Iridial irritation grade 1 was observed and resolved within 24 hours in one animal and within 48 hours in the other two animals. The irritation of the conjunctivae consisted of redness, chemosis and discharge and completely resolved within 7 days in one animal and within 14 days in the other two animals.
No corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage.
Other effects:
There was no evidence of ocular corrosion. 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. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Barium nitrate was found to cause irritation to the rabbit eye. Since the redness of the conjunctivae exceeded the classification threshold of 2 in two (of the three) animals which did not recover within 7 days, and according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011), barium nitrate should be classified as irritating to eyes (Category 2A). According to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures, barium nitrate should be classified as irritating to eyes (Category 2) and labeled as H319 (causes serious eye irritation).