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Diss Factsheets

Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Non GLP and non guideline study, but sufficient for hazard assessment together with a read-across on a in vivo study with a structural analogue substance (Key.001.Read-Across.CsNO3.in vivo Eye irritation.TOXI-COOP.2013) and in vitro data (Supporting.002.in vitro Eye irritation.TOXI-COOP.2013).
Justification for type of information:
Rubidium nitrate (CAS no. 13126-12-0, EC no. 236-060-1)

Rubidium (Rb+) is an alkali metal which belongs to Group 1 of the periodic table sharing comparable physical and chemical properties with other Group 1 elements, including lithium, sodium, potassium, cesium and francium.
Therefore, accumulation and excretion of rubidium is similar to potassium, such that body K+ appears to be a reliable index to estimate retention of Rb+. Physiological similarity of rubidium and potassium was reported by the team of Relman AS in the sixties. In fact, Rb+ follows the movement of K+ in the body and competes with K+ for transport across cell membranes. Physiological experiments indicate exchangeability of rubidium for potassium in blood, plasma, and tissue (Relman AS, 1956).
Medical and toxicological literatures generally indicate a very low degree of toxicity (Johnson et al., 1975; Khamidulina, 1987; Wagner, 2011). In many cases, the health risks of rubidium compounds are associated with the anion, e.g., hydroxide, or fluoride, rather than the rubidium cation.

Literature
Hall PWH and Relman AS. 1960. Acid excretion in rubidium- and cesium-substituted rats. J Clin Invest. 39:171–177.
Johnson GT, Lewis RT, Wagner WD. 1975. Acute toxicity of cesium and rubidium compounds. Toxicol App Pharmacol. 32:239-245.
Khamidulina Kh. Kh. 1987. Gig. Tr. Prof. Zabol. (9), 55 (Russian paper)
Relman AS, Roy AM, Schwartz. 1955. The acidifying effect of Rubidium in normal and potassium-deficient alkalotic rats. J Clin Invest. 34: 538–544.
Relman AS. 1956. The physiological behaviour of Rubidium and Cesium in relation to that of potassium. Yale J Biol Med. 29:248-62.
Wagner FS. 2011. Rubidium and Rubidium Compounds. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc.
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
water solubility
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 February 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 105 (Water Solubility)
Version / remarks:
OECD Method 105, adopted by the Council on 27 July 1995
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of method:
other: In a preliminary test a portion (approximately 100 mg) of the test item was found to dissolve readily in 200 μL of purified water, forming a single phase with no separated material, indicating a solubility of greater than 500 g/L of solvent.
Specific details on test material used for the study:
Identity: Rubidium nitrate
Appearance: White crystalline powder
Storage conditions: Room temperature (15 to 25C), desiccated, dark
Batch number: 215091B002
Purity: 100%
Expiry date: September 2017
Date received: 03 November 2016
Key result
Water solubility:
> 500 g/L
Conc. based on:
test mat.
Remarks on result:
completely miscible
Conclusions:
The test substance was found to have a solubility of greater than 500 g/L of water.
Executive summary:

The purpose of this study was to determine the water solubility of the test substance. The study was conducted in accordance with accepted principles in order to meet the requirements of REACH Regulation (EU) No 1907/2006 of the European Parliament and of the Council, REACH Regulation (EC) No 440/2008 (as amended) of 30 May 2008 (Method A.6) and the OECD Guidelines for Testing of Chemicals (Method 105). The test substance was found to have a solubility of greater than 500 g/L of water.

Reason / purpose for cross-reference:
read-across source
Reference
Endpoint conclusion:
no adverse effect observed (not irritating)
Endpoint conclusion:
no adverse effect observed (not irritating)
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
skin irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP and non guideline study, but sufficient for hazard assessment together with in vitro data (Key.001.Skin / corrosion.TOXI-COOP.2011).
Justification for type of information:
Rubidium nitrate (CAS no. 13126-12-0, EC no. 236-060-1)

Rubidium (Rb+) is an alkali metal which belongs to Group 1 of the periodic table sharing comparable physical and chemical properties with other Group 1 elements, including lithium, sodium, potassium, cesium and francium.
Therefore, accumulation and excretion of rubidium is similar to potassium, such that body K+ appears to be a reliable index to estimate retention of Rb+. Physiological similarity of rubidium and potassium was reported by the team of Relman AS in the sixties. In fact, Rb+ follows the movement of K+ in the body and competes with K+ for transport across cell membranes. Physiological experiments indicate exchangeability of rubidium for potassium in blood, plasma, and tissue (Relman AS, 1956).
Medical and toxicological literatures generally indicate a very low degree of toxicity (Johnson et al., 1975; Khamidulina, 1987; Wagner, 2011). In many cases, the health risks of rubidium compounds are associated with the anion, e.g., hydroxide, or fluoride, rather than the rubidium cation.

Literature
Hall PWH and Relman AS. 1960. Acid excretion in rubidium- and cesium-substituted rats. J Clin Invest. 39:171–177.
Johnson GT, Lewis RT, Wagner WD. 1975. Acute toxicity of cesium and rubidium compounds. Toxicol App Pharmacol. 32:239-245.
Khamidulina Kh. Kh. 1987. Gig. Tr. Prof. Zabol. (9), 55 (Russian paper)
Relman AS, Roy AM, Schwartz. 1955. The acidifying effect of Rubidium in normal and potassium-deficient alkalotic rats. J Clin Invest. 34: 538–544.
Relman AS. 1956. The physiological behaviour of Rubidium and Cesium in relation to that of potassium. Yale J Biol Med. 29:248-62.
Wagner FS. 2011. Rubidium and Rubidium Compounds. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
not specified
GLP compliance:
no
Specific details on test material used for the study:
High purity material in excess of 99%
Species:
rabbit
Strain:
other: albino
Details on test animals or test system and environmental conditions:
no data
Type of coverage:
semiocclusive
Preparation of test site:
other: abraded and intact skin was tested
Vehicle:
water
Controls:
other: positive (50% HCl) and negative (water) control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 5 % in water

Duration of treatment / exposure:
48 h (no rinsing up to the end of the observation periode)
Observation period:
24 and 48 h
Number of animals:
6 animals
Details on study design:
The backs of the animals were clipped free of hair. The skin on the right side of the backs was abraded at each of the test sites, while the skin on the
left side remained intact. The sites were abraded by uaing a crosshatch design, deep enough to penetrate the epidermis without bleeding. (Abrasions were made using two No. 11 Bard-Parker scalpel blades inserted in a cork stopper approximately 2 mm apart.) The test material (0.1 ml) was applied at each of the test sites. Each test site was covered with a gauze patch measuring 20 mm by 20 mm. Each animal was provided with a leather harness for the initial 24-hour exposure.
Irritation parameter:
overall irritation score
Basis:
mean
Remarks:
of six animals
Time point:
other: 24 and 48 h
Score:
0
Max. score:
4
Remarks on result:
other: The max. score gives the theoretically highest reachable value.
Irritation parameter:
other: cellular toxicity on abraded skin
Basis:
mean
Remarks:
of six animals
Time point:
other: 24 h
Score:
>= 0 - <= 1
Max. score:
4
Reversibility:
fully reversible within: 48 h
Remarks on result:
other: The max. score gives the theoretically highest reachable value.
Interpretation of results:
GHS criteria not met
Conclusions:
Rubidium iodide was non-irritating to skin in this in vivo study in rabbits.
Executive summary:

Rubidium iodide was non-irritating to skin in this in vivo study in rabbits. On intact skin a 5 % solution of Rubidium iodide in water induced no irritating effects, e.g. erythema, edema. Only a mild cellular toxic effect was observed on abraded skin which was fully reversible within 48 h. Therefore, RbI is considered safe for intact or abraded human skin.

Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, equivalent or similar to OECD and EU guideline.
Justification for type of information:
Rubidium nitrate (CAS no. 13126-12-0, EC no. 236-060-1)

Rubidium (Rb+) is an alkali metal which belongs to Group 1 of the periodic table sharing comparable physical and chemical properties with other Group 1 elements, including lithium, sodium, potassium, cesium and francium.
Therefore, accumulation and excretion of rubidium is similar to potassium, such that body K+ appears to be a reliable index to estimate retention of Rb+. Physiological similarity of rubidium and potassium was reported by the team of Relman AS in the sixties. In fact, Rb+ follows the movement of K+ in the body and competes with K+ for transport across cell membranes. Physiological experiments indicate exchangeability of rubidium for potassium in blood, plasma, and tissue (Relman AS, 1956).
Medical and toxicological literatures generally indicate a very low degree of toxicity (Johnson et al., 1975; Khamidulina, 1987; Wagner, 2011). In many cases, the health risks of rubidium compounds are associated with the anion, e.g., hydroxide, or fluoride, rather than the rubidium cation.

Literature
Hall PWH and Relman AS. 1960. Acid excretion in rubidium- and cesium-substituted rats. J Clin Invest. 39:171–177.
Johnson GT, Lewis RT, Wagner WD. 1975. Acute toxicity of cesium and rubidium compounds. Toxicol App Pharmacol. 32:239-245.
Khamidulina Kh. Kh. 1987. Gig. Tr. Prof. Zabol. (9), 55 (Russian paper)
Relman AS, Roy AM, Schwartz. 1955. The acidifying effect of Rubidium in normal and potassium-deficient alkalotic rats. J Clin Invest. 34: 538–544.
Relman AS. 1956. The physiological behaviour of Rubidium and Cesium in relation to that of potassium. Yale J Biol Med. 29:248-62.
Wagner FS. 2011. Rubidium and Rubidium Compounds. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Remarks:
, e.g. 9 instead of 10 animals
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
Remarks:
, e.g. 9 instead of 10 animals
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
High purity material in excess of 99%
Species:
rat
Strain:
other: Charles River albino rats
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, cesarian-derived albino rats
- Weight at study initiation: 175 -250 g
- Fasting period before study: yes (overnight, 16 h)
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: good solubility in water
Doses:
First main test: 820, 1170, 1660, 2350, 3340, 4750 mg/kg
Second main test: 1890, 2120, 2515, 2680, 3010 mg/kg
No. of animals per sex per dose:
9 male rats
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 1 and 4 h following administration and dayly thereafter for the 14-day period
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, histopathology, behavioral observations
Statistics:
The LD50 values and their 95% confidence limits were calculated by probit analysis of Finney (1971).
Preliminary study:
not applicable; however, range finding study was performed:
The test material was administered as a single dose, orally by stomach tube, to caesarean-derived rats weighing between 175 and 250 grams. Eight test groups of three animals per group (24 total) were used. The animals were fasted from food for approximately 16 hours prior to dosing. The test material was dissolved in deionized and distilled water. Observations for morbidity and mortality were recorded at 1 and 4 hours following administration and daily thereafter for the 7-day period. Gross necropsy observations were made on all animals which died or were sacrificed at the end of the 7-day observation period.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
4 708 mg/kg bw
Based on:
test mat.
Remarks:
RbI
95% CL:
ca. 4 413 - ca. 5 026
Mortality:
yes. All deaths occured within the first 72 hr after dosing.
Body weight:
No data on body weight.
Other findings:
The most notable necropsy findings in rats that died following the administration of RbI were congested, cyanotic lungs with petechial hemorrhages and fluid-distended stomach which appeared to result from spasm of the pyloric sphincter following the dosing. All deaths occured within the first 72 hr after dosing.
Interpretation of results:
not classified
Conclusions:
The acute oral LD50 of Rubidium iodide in albino rats was determined to be 4708 mg/kg bw.
Executive summary:

In an acute oral toxicity study, groups of 9 fasted male albino rats were given a single oral dose of Rubidium iodide (> 99 %) in water at 11 different doses and observed for 14 days.

Oral LD50 Males = 4708 mg/kg bw (95% C.L: 4413 - 5026 mg/kg)

Rubidium iodide is not classified after oral administration based on the LD50 obtained in male rats.

Reason / purpose for cross-reference:
read-across source
Reference
Endpoint:
eye irritation: in vivo
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Non GLP and non guideline study, but sufficient for hazard assessment together with a read-across on a in vivo study with a structural analogue substance (Key.001.Read-Across.CsNO3.in vivo Eye irritation.TOXI-COOP.2013) and in vitro data (Supporting.002.in vitro Eye irritation.TOXI-COOP.2013).
Justification for type of information:
Rubidium nitrate (CAS no. 13126-12-0, EC no. 236-060-1)

Rubidium (Rb+) is an alkali metal which belongs to Group 1 of the periodic table sharing comparable physical and chemical properties with other Group 1 elements, including lithium, sodium, potassium, cesium and francium.
Therefore, accumulation and excretion of rubidium is similar to potassium, such that body K+ appears to be a reliable index to estimate retention of Rb+. Physiological similarity of rubidium and potassium was reported by the team of Relman AS in the sixties. In fact, Rb+ follows the movement of K+ in the body and competes with K+ for transport across cell membranes. Physiological experiments indicate exchangeability of rubidium for potassium in blood, plasma, and tissue (Relman AS, 1956).
Medical and toxicological literatures generally indicate a very low degree of toxicity (Johnson et al., 1975; Khamidulina, 1987; Wagner, 2011). In many cases, the health risks of rubidium compounds are associated with the anion, e.g., hydroxide, or fluoride, rather than the rubidium cation. In the specific case of rubidium hydroxide; it needs to be taken into account the higher alkaline efficiency due to the hydroxide.

Literature
Hall PWH and Relman AS. 1960. Acid excretion in rubidium- and cesium-substituted rats. J Clin Invest. 39:171–177.
Johnson GT, Lewis RT, Wagner WD. 1975. Acute toxicity of cesium and rubidium compounds. Toxicol App Pharmacol. 32:239-245.
Khamidulina Kh. Kh. 1987. Gig. Tr. Prof. Zabol. (9), 55 (Russian paper)
Relman AS, Roy AM, Schwartz. 1955. The acidifying effect of Rubidium in normal and potassium-deficient alkalotic rats. J Clin Invest. 34: 538–544.
Relman AS. 1956. The physiological behaviour of Rubidium and Cesium in relation to that of potassium. Yale J Biol Med. 29:248-62.
Wagner FS. 2011. Rubidium and Rubidium Compounds. Kirk-Othmer Encyclopedia of Chemical Technology. John Wiley & Sons, Inc.
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
the test materials at various concentrations (0.1, 0.5, 1.0, and 5.0%) was placed in one eye of each animal by pulling the lower lid of the eyeball to form a cup into which the compounds under investigation were instilled. The eyelids were held together for approximately 1 set and the animal was then released. The animals were exposed to the test compound for either 5 min or 24 hr before washing the eye with approximately 300 ml of distilled water instilled over a 2-min period. The eyes were examined with the aid of fluorescein but without the aid of a hand slit-lamp at 1, 24, 48, and 72 hr and at 7 days; if any injury persisted, the eyes were reexamined at 14 and 21 days.
Grading of the severity of the eye irritation was performed by a modification of the method of Draize (1944) based upon the presence and degree of ulceration or opacity of the cornea and iris and erythema, chemosis and ulceration or necrosis of the conjunctival mucosa.
GLP compliance:
no
Specific details on test material used for the study:
High purity material in excess of 99%
Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2 - 3 kg

Vehicle:
water
Controls:
other: the untreated eye of each animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 5 %

Duration of treatment / exposure:
5 min (5 animals) and 24 h (3 animals)
Observation period (in vivo):
1 h, 24 h, 48 h, 72 h, 7 days; in case of persistent damage: 24 days, 21 days
Number of animals or in vitro replicates:
8 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: 250 ml water
- Time after start of exposure: 5 min or 24 h, respectively

SCORING SYSTEM:
- Cornea: 0-4
- Iris: 0-2
- Conjunctive Redness: 0-3
- Chemosis: 0-4

Irritation parameter:
other: Draize method (1944)
Basis:
animal #1
Time point:
other: 5 minutes
Reversibility:
not specified
Remarks on result:
positive indication of irritation
Remarks:
Extremely irritant and corrosive
Irritant / corrosive response data:
- RbOH (5%) - 5 min exposure: Extremely irritant and corrosive (only one animal used) - 24 hours exposure: no data
- RbOH (1%) - 5 min exposure: Marginal (5 animal used) - 24 hours exposure: negative (3 animals used)
Interpretation of results:
study cannot be used for classification
Conclusions:
Rubidium hydroxide is higly irritating and corrosive for the eyes of rabbits. However, the corossivity is due to the hydroxide. In the context of the registration of rubidium nitrate, this study needs to be disregarded.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Acute toxicity of cesium and rubidium compounds
Author:
Johnson, G.T.; Lewis, R.T. and Wagner, W.D.
Year:
1975
Bibliographic source:
Toxicology and applied pharmacology 32, 239-245 (1975)
Reference Type:
publication
Title:
Unnamed
Year:
1972

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not specified
Principles of method if other than guideline:
the test materials at various concentrations (0.1, 0.5, 1.0, and 5.0%) was placed in one eye of each animal by pulling the lower lid of the eyeball to form a cup into which the compounds under investigation were instilled. The eyelids were held together for approximately 1 set and the animal was then released. The animals were exposed to the test compound for either 5 min or 24 hr before washing the eye with approximately 300 ml of distilled water instilled over a 2-min period. The eyes were examined with the aid of fluorescein but without the aid of a hand slit-lamp at 1, 24, 48, and 72 hr and at 7 days; if any injury persisted, the eyes were reexamined at 14 and 21 days.
Grading of the severity of the eye irritation was performed by a modification of the method of Draize (1944) based upon the presence and degree of ulceration or opacity of the cornea and iris and erythema, chemosis and ulceration or necrosis of the conjunctival mucosa.
GLP compliance:
no

Test material

Constituent 1
Reference substance name:
Rubidium iodide
EC Number:
232-198-1
EC Name:
Rubidium iodide
Cas Number:
7790-29-6
Molecular formula:
IRb
IUPAC Name:
Rubidium iodide
Specific details on test material used for the study:
High purity material in excess of 99%

Test animals / tissue source

Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2 - 3 kg

Test system

Vehicle:
water
Controls:
other: the untreated eye of each animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): 5 %

Duration of treatment / exposure:
5 min (5 animals) and 24 h (3 animals)
Observation period (in vivo):
1 h, 24 h, 48 h, 72 h, 7 days; in case of persistent damage: 24 days, 21 days
Number of animals or in vitro replicates:
8 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: 250 ml water
- Time after start of exposure: 5 min or 24 h, respectively

SCORING SYSTEM:
- Cornea: 0-4
- Iris: 0-2
- Conjunctive Redness: 0-3
- Chemosis: 0-4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 8 animals
Time point:
other: 1 h, 24 h, 48 h, 72 h, 7 days
Score:
0
Max. score:
4
Remarks on result:
other: The max. score gives the theoretically highest reachable value.
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 8 animals
Time point:
other: 1 h, 24 h, 48 h, 72 h, 7 days
Score:
0
Max. score:
2
Remarks on result:
other: The max. score gives the theoretically highest reachable value.
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of 8 animals
Time point:
other: 1 h, 24 h, 48 h, 72 h, 7 days
Score:
0
Max. score:
3
Remarks on result:
other: The max. score gives the theoretically highest reachable value.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 1 h, 24 h, 48 h, 72 h, 7 days
Score:
0
Max. score:
4
Remarks on result:
other: The max. score gives the theoretically highest reachable value.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Rubidium iodide was non-irritating to eyein this in vivo study in rabbits.
Executive summary:

Rubidium iodide was non-irritating to eye in this in vivo study in rabbits. There were no effects on cornea, iris and conjuctivae or the incidence of chemosis to any time point.