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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:
2010-05-18 to 2010-06-28
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study reliable without restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
, 2002-04-24
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 chloride di-hydrate
- EC No.: 233-788-1
- Molecular formula: BaCl2 * 2H20
- Molecular weight: 244.26
- Physical state: White crystalline powder (determined at NOTOX)
- Stability under storage conditions: Stable
- Storage condition of test material: At room temperture in the dark
- pH: 5.5 - 7.5 (100 g/L at 20 °C)
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: 9 - 11 weeks old
- Weight at study initiation: 2.210 kg - 2.261 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: 18.8 – 23.4ºC
- Relative humidity: 38 - 81%
- Air changes: Approximately 15 air changes per 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): On average 99.5 mg (range 98.9 - 99.9 mg) of the test substance was installed 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):
Approximately 1, 24, 48 and 72 hours and 7 and 14 days (all animals) 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 performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 3 weeks later, after considering the degree of eye irritation observed in the first animal.

SCORING SYSTEM: draize scoring system was used. 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.

TOOL USED TO ASSESS SCORE: Immediately after the 24-hour observation, a solution of 2% fluorescein (Merck, Darmstadt, Germany) in water was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Where standard lighting was considered inadequate for observing minor effects, eye examinations were performed using an ophthalmic examination lamp.

OBSERVATIONS.
Mortality/Viability: Twice daily
- Toxicity: At least once daily
- Body weight: Day of treatment (prior to instillation) and after the final observation
Necrospy: no necropsy was performed.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #1
Time point:
other: 24, 48, and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #2
Time point:
other: 24, 48, and 72 hours
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
0.3
Max. score:
1
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
2.7
Max. score:
3
Reversibility:
fully reversible within: 21 days
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
animal #3
Time point:
other: 24, 48, and 72 hours
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
The corneal injury consisted of opacity (maximum grade 1: Scattered or diffuse areas of opacity, details of iris clearly visible) and epithelial damage (maximum 10, 15 or 20% of the corneal area). Slight dulling of the normal luster of the cornea was also observed. The corneal injury fully resolved within 72 hours in two animals and within 7 days in the other animal.
Iridial irritation grade 1(Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive)) 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 (maximum grade 3: Diffuse beefy red), chemosis (maximum grade 3: Swelling with lids about half closed) and discharge (Discharge with moistening of the lids and hairs just adjacent to lids to any amount different from normal and/or lacrimation) and completely resolved within 14 days in one animal and within 21 days in the other two animals.
There was no evidence of ocular corrosion.
No staining of (peri) ocular tissue by the test substance was observed and no test substance remnants were seen.
Other effects:
Toxicity/Mortality:
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 2 (irritating to eyes) based on GHS criteria
Conclusions:
According to the Regulation (EC) No 1272/2008, barium chloride dihydrate should be classified as Irritating to eyes (Category 2).
According to the criteria specified by Directive 67/548/EEC and subsequent regulations, the test item is classified as eye irritant ("irritating to eyes"