Registration Dossier

Administrative data

Description of key information

Skin irritation/corrosion:
Cesium iodide was tested in the in vitro skin irritation test using the EPISKIN model. The results obtained from this study indicated that the test item is considered to be a non-irritant. In addition, published in vivo data with cesium iodide support this conclusion.
Eye irritation in vitro:
In the in vitro eye corrosives and severe irritants study, using the Isolated Chicken Eye model with cesium iodide, no ocular corrosion or severe irritation potential was observed. Thus, according to the guideline OECD 438, cesium iodide cannot be classified as an ocular corrosive or severe eye irritant.
Eye irritation in vivo:
In conclusion, test item cesium iodide applied to the rabbits' eye mucosa, caused slight to severe conjunctival and slight corneal irritant effects, fully reversible within 1 week.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vitro / ex vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011-07-27 to 2011-07-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP, CLP and Guideline compliant study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)
Version / remarks:
22 July 2010
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)
Version / remarks:
Version 1.8 (February 2009)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
other: reconstituted human epidermis
Strain:
other: reconstituted human epidermis
Details on test animals and environmental conditions:
EpiSkinTM Small Model (EpiSkinTMSM), EPISKIN SNC Lyon, France, is a three-dimensional human epidermis model. Adult human-derived epidermal keratinocytes are seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen. A highly differentiated and stratified epidermis model is obtained after 13-day culture period comprising the main basal, supra basal, spinous and granular layers and a functional stratum corneum. Its use for skin irritation testing involves topical application of test materials to the surface of the epidermis, and the subsequent assessment of their effects on cell viability.

Source: Skinethic, Nice, France
Batch No.: 11-EKIN-030
Expiry date: 01 August 2011
Type of coverage:
other: not applicable (reconstituted human epidermis)
Preparation of test site:
other: not applicable (reconstituted human epidermis)
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
The test item was applied in its original form, no formulation was required. 10 mg of the test item was applied to each EpiSkin epidermis units.
Duration of treatment / exposure:
15 min
Observation period:
Not applicable (reconstituted human epidermis)
Number of animals:
Not applicable (reconstituted human epidermis). However, in this assay 3 replicates for the test item and 3 negative controls + 3 positive controls were used.
Details on study design:
The following steps were performed under axenic conditions.

Pre-incubation (day [-1]):
The “maintenance medium” was pre-warmed to 37°C. The appropriate number of assay plate wells were filled with the pre-warmed medium (2 mL per well). The epidermis units were placed, with the media below them in contact with the epidermis, into each prepared well and then incubated overnight at 37°C in an incubator with 5% CO2.

Application (day 0):
Test Item
Epidermal surface was first moistened with 10 µL deionised water and then 10 mg of the test item was applied evenly on the skin. Test substance was spread gently with a curved flat spatula in order to cover evenly all the epidermal surface.

Positive and negative control
A volume of 10 µL positive control (SDS 5 % aq.) or negative control (1x PBS) was applied on the skin surface by using a suitable pipette. Chemicals were spread gently with the pipette tip in order to cover evenly all the epidermal surface if necessary.

Exposure (day 0):
The plates with the treated epidermis units were incubated for the exposure time of 15 minutes at room temperature.

Rinsing (day 0):
After the incubation time the EPISKIN-SM units were removed and rinsed thoroughly with PBS 1x solution (0.9%) to remove all of the test material from the epidermal surface. The rest of the PBS was removed from the epidermal surface with a suitable pipette tip linked to a vacuum source (care was taken to avoid the damage of epidermis).

Post-incubation (day 0-2):
After rinsing the units were placed into the plate wells with fresh pre-warmed “maintenance medium” (2 mL/well) below them and then incubated for 42 hours at 37°C in an incubator with 5% CO2.

MTT test after 42 hours incubation (day 2):
After the 42 hours incubation the EPISKIN-SM units were transferred into the MTT solution filled wells (2 mL of 0.3 mg/mL MTT per well) and then incubated for 3 hours at 37°C in an incubator with 5 % CO2 protected from light.

Formazan extraction (day 2):
At the end of incubation with MTT a formazan extraction was undertaken:
A disk of epidermis from each replicate was cut from the unit using a biopsy punch. The epidermis was separated with the aid of forceps and both parts (epidermis and collagen matrix) were placed into a tube of 500 µL acidified isopropanol.

The capped tubes were thoroughly mixed by using a vortex mixer to achieve a good contact of all of the material with the acidified isopropanol then incubated for about two hours at room temperature protected from light with gentle agitation (~150 rpm) for formazan extraction.

Cell viability measurements (day 2):
Following the formazan extraction, 2×200 µL samples from each tube were placed into the wells of a 96-well plate (labelled appropriately). The OD (Absorbance / Optical Density) of the samples in a 96-well plate spectrophotometer was read at 570 nm using acidified isopropanol solution blank (6×200 µL).
Irritation / corrosion parameter:
other:
Value:
101
Remarks on result:
other:
Remarks:
Basis: mean. Time point: 42 h total incubation time. (migrated information)
Irritant / corrosive response data:
The results obtained from the in vitro skin irritation test in the EPISKIN model with cesium nitrate indicated a mean viability of 101 % (SD 6.48) after a total 42 h incubation time and therfore the test item is considered to be a non-irritant (NI) [UN GHS: No Category].
Other effects:
none
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this in vitro skin irritation test in the EPISKIN model with test item cesium iodide the results indicated that the test item is considered to be a non-irritant (NI) [UN GHS: No Category].
Executive summary:

In this in vitro skin irritation test using the EPISKIN model, the test item cesium iodide did not show a significantly reduced cell viability in comparison to the negative control. All obtained test item viability results were above 50% when compared to the viability values obtained from the negative control. Positive and negative controls showed the expected cell viability values within acceptable limits, thus the experiment was considered to be valid. The results indicated that the test item revealed no skin irritantion potential under the utilised testing conditions. According to the current OECD Guideline No. 439, the test item is considered a non-irritant to skin and is therefore not classified.

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:
2012-10-09 to 2012-10-16
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP and guideline compliant study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S & K LAP Kft. 2173 Kartal, Császár út 135, HUNGARY
- Age at study initiation: Young adult rabbits
- Weight at study initiation: 2870-2925 g
- Housing: Animals were housed individually in metal cages.
- Diet: Fattening mixed diet, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 9-12 changes/hour
- Photoperiod: Artificial light, from 6 a.m. to 6 p.m.
Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0. 1 g
Duration of treatment / exposure:
In the first step an initial test was performed using one animal. The test item was firstly well grinded and was poured into the conjunctival sac of the left eye. The eyelids were held closed gently for several seconds to prevent the loss of the test item. The contralateral eye served as control. Immediately after the administration of the test item, an assessment of the initial pain reaction was made according to the six point scale.
After consideration of the ocular responses produced in the first animal, two additional animals were treated.
Before the administration, the eyes of the second and the third animal were not anaesthetised, because the score of initial pain reaction was 2 in the first animal. The eyes of the test animals were not washed out after the application of test item.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours after the application.
Number of animals or in vitro replicates:
3 animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
None
SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (24th April 2002).
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72 h
Score:
0.33
Max. score:
4
Reversibility:
fully reversible within: 24 h
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24, 48, 72 h
Score:
0
Max. score:
2
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24h
Score:
2
Max. score:
3
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48 h
Score:
0.33
Max. score:
3
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72 h
Score:
1
Max. score:
3
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24 h
Score:
1.33
Max. score:
4
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48 h
Score:
0
Max. score:
4
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72 h
Score:
0.33
Max. score:
4
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 24 h
Score:
2
Max. score:
3
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 48 h
Score:
0.33
Max. score:
3
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Irritation parameter:
conjunctivae score
Remarks:
discharge
Basis:
mean
Remarks:
of 3 animals
Time point:
other: 72 h
Score:
1.33
Max. score:
3
Remarks on result:
other: The max score gives the theoretically highest reachable score.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In conclusion, test item cesium iodide applied to the rabbits' eye mucosa, caused slight to severe conjunctival and slight corneal irritant effects, fully reversible within 1 week.
According to the Commission Directive 2001/59/EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.
According to Regulation (EC) No. 1272/2008, the test item has not been classified into any category.
Executive summary:

The eyes were examined at 1, 24, 48 and 72 hours then 1 week after the application. One hour after treatment, some hyperemic blood vessels (score 1) were observed in all animals. The obvious swelling with partial eversion of lids (score 2) was detected in animal No.: 1742 and the swelling was different from normal (score 1) in two animals (No.: 1735, 1732). The discharge with moistening of the lids and hairs just adjacent to lids (score 2) were observed in two animals (No.: 1742, 1735) and the discharge moistened lids and hairs on considerable area around the treated eye (score 3) was recorded in animal No.: 1732. Diffuse areas of opacity were detected and the details of iris were clearly visible (score 1) in two animals (No.: 1742, 1732). Area of cornea involved was greater than one quarter, but less than half (score 2) in both animals. 24 hours after treatment, some hyperemic blood vessels (score 1) were observed in two animals (No.: 1735, 1732) and diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) occurred in animal No.: 1742. The obvious swelling with partial eversion of lids (score 2) was detected in animal No.: 1742 and the swelling was different from normal (score 1) in animal (No.: 1732). The discharge with moistening of the lids and hairs just adjacent to lids (score 2) were observed in two animals (No.: 1742, 1732) and the amount of the discharge was different from normal (score 1) in animal No.: 1735. Diffuse areas of opacity were detected and the details of iris were clearly visible (score 1) in animal No.: 1742. Area of cornea involved was at least one quarter, but not zero (score 1) in this animal. 48 hours after treatment, some hyperemic blood vessels (score 1) were observed in animal No.: 1732 and diffuse, crimson coloured conjunctivae with not easily discernible individual vessels (score 2) occurred in animal No.: 1742. The swelling was different from normal (score 1) in animal (No.: 1742). The discharge with moistening of the lids and hairs just adjacent to lids (score 2) were observed in animal No.: 1742 and the amount of the discharge was different from normal (score 1) in animal No.: 1732. 72 hours after the treatment, the state of animals was unchanged. 1 week after the treatment the study was terminated, since no primary irritation symptoms occurred. During the study the control eyes of the animals were symptom-free. General state and the behaviour of the animals were normal throughout the study period. There were no effects on body weight attributable to the treatment with the test item during the contact and observation period.

In conclusion, test item cesium iodide applied to the rabbits' eye mucosa, caused slight to severe conjunctival and slight corneal irritant effects, fully reversible within 1 week.

According to the Commission Directive 2001/59/EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

According to Regulation (EC) No. 1272/2008, the test item has not been classified into any category.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation/corrosion

In the in vitro skin irritation test using the EPISKIN model, the test item cesium iodide did not show a significantly reduced cell viability in comparison to the negative control. All obtained test item viability results were above 50% when compared to the viability values obtained from the negative control. Positive and negative controls showed the expected cell viability values within acceptable limits, thus the experiment was considered to be valid. The results indicated that the test item revealed no skin irritantion potential under the utilised testing conditions. According to the current OECD Guideline No. 439, the test item is considered a non-irritant to skin and is therefore not classified according to Regulation No (EC) 1272/2008 (CLP) or Directive 67/548/EEC (DSD) criteria.

In addition, published in vivo data with cesium iodide support this conclusion.

Eye irritation in vitro

The in vitro Isolated Chicken Eye Test (ICET) was perfomed according to OECD guideline 438 and EU method B.48 to evaluate the potential ocular corrosivity or severe irritancy of the test item cesium iodide. The test compound was applied in its powdered form via a single dose of 0.03 g onto the cornea of isolated chicken eyes.

During the testing no ocular corrosion or severe irritation potential of the test item was observable. Thus, according to the guideline OECD 438, cesium iodide cannot be classified as an ocular corrosive or severe eye irritant. Furthermore, the results suggest that the test item was slightly irritating. However, to obtain a definitive classification in relation to the irritation potential, a further in vivo rabbit study is required.

Eye irritation in vivo

In conclusion, test item cesium iodide applied to the rabbits' eye mucosa, caused slight to severe conjunctival and slight corneal irritant effects, fully reversible within 1 week.

According to the Commission Directive 2001/59/EC criteria for classification and labelling requirements for dangerous substances and preparations, the test item does not have to be classified and has no obligatory labelling requirement for eye irritation.

According to Regulation (EC) No. 1272/2008, the test item has not been classified into any category.

In addition, published in vivo data with cesium iodide support this conclusion.


Justification for selection of skin irritation / corrosion endpoint:
Most reliable study.

Justification for selection of eye irritation endpoint:
GLP and guideline compliant study.

Justification for classification or non-classification

Based on skin irritation and eye irritation data available for cesium iodide no classification and labelling is required according to Regulation No (EC) 1272/2008 (CLP) criteria.