Caesium iodide

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-02-01 to 2012-02-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

, adopted 2012

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Version / remarks:

, adopted 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

, adopted 2003

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Caesium nitrate

EC Number:

232-146-8

EC Name:

Caesium nitrate

Cas Number:

7789-18-6

Molecular formula:

Cs.HNO3

IUPAC Name:

cesium nitrate

Test material form:

solid: crystalline

In vivo test system

Test animals

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: TOXI-COOP ZRT. H-1103, Budapest, Cserkesz u. 90.
- Age at study initiation: young adult mice, 9-10 weeks (at start of the experiment)
- Weight at study initiation: 16.8 - 21.5 g
- Housing: grouped caging (5 animals/cage)in type II. polypropylene/polycarbonate cages
- Diet: Animals received ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany, ad libitum
- Water: tap water for human supply, ad libitum
- Acclimation period: 7 days (pre-test) and 21 days (main study)

ENVIRONMENTAL CONDITIONS
- Temperature: :22 ± 3 °C
- Humidity: 30 – 70 %
- Photoperiod: 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Results and discussion

Positive control results:

The positive control group animals were treated with 25 % (w/v) Hexyl cinnamic aldehyde (HCA) solution concurrent to the test item treated groups. No confounding effects of irritation or systemic toxicity were observed in the positive control group. Significant lymphoproliferative response (SI 3) was noted for HCA with stimulation index value of 11.82. The result of the positive control item demonstrated the appropriate performance of the test in accordance with the Guidelines and confirmed sensitivity and validity of the assay.

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The Stimulation index values per treatment group were as follows: negative control: 1.0 SI positive control: 11.82 SI Test item: 25 %: 0.91 SI 10 %: 0.72 SI 5 %: 0.97 SI 2.5 %: 1.05 SI

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: The mean DPM values per treatment group were as follows: negative control: 818.4.0 DPM positive control: 18398.6 DPM Test item: 25 %: 743.0 DPM 10 %: 588.0 DPM 5 %: 795.0 DPM 2.5 %: 858.6 DPM

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

A skin sensitisation test according to GLP with cesium iodide is not available. Consequently, read-across was applied using results from a test with cesium nitrate. Cesium nitrate tested at 25 %, 10 %, 5% and 2.5 % as a solution in 1 % Pluronic was shown to have no sensitisation potential. Based on these results cesium iodide is considered to have no sensitisation potential also.

Executive summary:

A skin sensitisation test according to GLP with cesium iodide is not available. Consequently, read-across was applied using results from a test with cesium nitrate.

The aim of this study was to determine the skin sensitisation potential of cesium nitrate in the Local Lymph Node Assay (LLNA) according to the OECD Guideline 429 and EU Method B.42. The individual approach was used in this test whereby the lymph nodes of each animal were evaluated individually (in comparison to a pooled test group approach). The maximum attainable test item concentration, resulting in a homogenous formulation in an appropriate vehicle, was examined.

A preliminary solubility test was performed to select a suitable vehicle. The maximum attainable test concentration based on solubility was 25 % (w/v) in aqueous 1 % Pluronic. No higher test concentration was available in this test.

Based on results of a preliminary irritation/toxicity test 25 % was selected as the highest test concentration in the main test.

In the main test, 35 female CBA/Ca mice were allocated to seven groups of five animals each:

-four groups received cesium nitrate at 25 %, 10 %, 5 % or 2.5 %,

-the negative control group received the vehicle (1 % Pluronic) only,

-the positive control group received 25 % alpha-Hexylcinnamaldehyde

-the negative control group for the positive control group received Acetone: Olive oil 4:1 mixture (v/v/) (AOO) only.

Each substance was applied on the external surface of each ear (25 µL/ear) of the animals for three consecutive days (Day 1, 2 and 3).

There was no treatment on Days 4, 5 and 6. On Day 6, the cell proliferation in the local lymph nodes was measured by determining incorporation of tritiated methyl thymidine (3HTdR) and the obtained values were used to calculate stimulation indices (SI). No mortality was observed during the test. No local effects at the application sites (ears) were observed in any treatment group. Larger lymph nodes than the control were observed in the positive control group only. No statistically significant lymphoproliferation was observed in any group treated with the test item. The obtained SI values for the test item were 0.91, 0.72, 0.97 and 1.05 at concentrations of 25 %, 10 %, 5 % and 2.5 %, respectively. No dose-related response was observed. The positive control item induced the appropriate stimulation (SI = 11.82), thus confirming the validity of the assay. Since the mean SI value was below 3 at the maximum attainable test concentration of 25 % and at concentrations of 10 %, 5 % and 2.5 % and no dose-related response was observed, the test item was considered to be a non-sensitiser in the LLNA. Based on these results cesium iodide is considered to have no sensitisation potential also.