Rubidium nitrate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 read-across to other cesium nitrate.

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-reference

Cross-reference 1

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.

Cross-reference 2

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint conclusion:

no adverse effect observed (not sensitising)

Cross-reference 3

Reason / purpose for cross-reference:

read-across source

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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 read-across to other cesium nitrate.

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:

other: Landsteiner and Jacobs (1935) Studies on the sensitization of animals with simple chemical compounds. J. Exp. Med. 61, 643-657

Deviations:

not specified

Principles of method if other than guideline:

similar to that described by Landsteiner and Jacobs (1935) Studies on the sensitization of animals with simple chemical compounds. J. Exp. Med. 61, 643-657

A 0.1 ml vol of a 0.1% solution of the test compound was injected intracutaneously to separate skin sites of the animals three times weekly, for a total of nine treatments. Following a 2-wk period in which no further injections were made, a challenge dose of 0.1 ml of test compound was administered to both test and control animals in the same manner. Skin reactions were examined and recorded at 24,48, and 72 hr following the challenge dose.

GLP compliance:

no

Type of study:

other: SKIN SENSITIZATION BY INTRAPERITONEAL INJECTIONS

Justification for non-LLNA method:

The current endpoint has been fulfill with current available data. The current available data was made using a non-LLNA method. In addition and due to the available data rubisdium salts are not considered as a skin sensitizer. Therefore, no other test will be conducted for this endpoint.

Specific details on test material used for the study:

high purity material "99%"

Species:

guinea pig

Strain:

other: albino

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 300 - 400 g

Route:

intradermal

Vehicle:

water

Concentration / amount:

0.1 mL vol of 0.1% solutionof the test compound

Day(s)/duration:

2 weeks

Route:

other: not specified

Concentration / amount:

0.1 ml of the test compound

Day(s)/duration:

after 2 weeks after first injection and then, skin examined at 24, 48 and 72 hours.

Adequacy of challenge:

not specified

No. of animals per dose:

control: 5 males
test group: 10 males

Details on study design:

RANGE FINDING TESTS: no data

MAIN STUDY
Fifteen young adult male albino guinea pigs weighing between 300 and 400 grams were used. Five animals served as a control group and 10 animals were assigned to the test group. The backs of the animals were clipped free of hair and the clipping repeated at various intervals during the study. The test materials, 0.1 ml (0.1 %), were injected intradermally to separate skin sites of the animals three times weekly for a total of nine treatments. The five control animals were treated in a manner identical to the test group but using the solvent, distilled water, as a control material. Twenty-four hours following each injection the reaction was measured for size. The animals in both the test and control groups were rested for a two-week period following the ninth injection. At the end of the two-week rest period a challenge dose of 0.1 ml was administered
to both the test and control animals in the same manner as before. Test sites were examined and reactions recorded at 24, 48 and 72 hours.

Positive control substance(s):

no

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 mLof test compound

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1 mL of the test compound

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

1 mL of the test compound

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

If the response to the challenge injection is greater in terms of intensity or local inflammatory response than to tbe sensitizing doses, or the numher of animals responding is substantially greater, then the material is considered to be a skin sensitizer.

There was no evidence of erythema, swelling or dicolorartion of the test sites after each of the nine sensitizing cutaneous injections or after the challenge dose. These results indicate that rubidium hydroxide did not induce cutaneous sensitisation in guinea pigs in any of the 10 test animals. On this basis the results of these guinea pig study indicate that rubidium hydroxide is a non-sensitizer.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Rubidium hydroxide did not induce cutaneous sensitisation in guinea pigs.

Executive summary:

In a dermal sensitisation study with rubidium iodide (0.1 %) in water, young adult male albino guinea pigs (in total 15 animals) were tested using the method of Landsteiner and Jacobs (1935). The test compound was administered intradermally three times a week, for a total of nine treatments. Following a two-week period with no further injections a challenge of 0.1% was administered the same way. There was no evidence of erythema, swelling or dicolorartion of the test sites after each of the nine sensitizing cutaneous injections or after the challenge dose. The results of these guinea pig study indicate that rubidium hydroxide is a non-sensitizer.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Acute Toxicity studies of cesium and rubidium compounds

Author:

Johnson, G.T.; Lewis, R.T. and Perone, V.P.

Year:

1975

Bibliographic source:

Toxicology and applied pharmacology 32, 239-245 (1975)

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1972

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: Landsteiner and Jacobs (1935) Studies on the sensitization of animals with simple chemical compounds. J. Exp. Med. 61, 643-657

Deviations:

not specified

Principles of method if other than guideline:

similar to that described by Landsteiner and Jacobs (1935) Studies on the sensitization of animals with simple chemical compounds. J. Exp. Med. 61, 643-657

A 0.1 ml vol of a 0.1% solution of the test compound was injected intracutaneously to separate skin sites of the animals three times weekly, for a total of nine treatments. Following a 2-wk period in which no further injections were made, a challenge dose of 0.1 ml of test compound was administered to both test and control animals in the same manner. Skin reactions were examined and recorded at 24,48, and 72 hr following the challenge dose.

GLP compliance:

no

Type of study:

other: SKIN SENSITIZATION BY INTRAPERITONEAL INJECTIONS

Justification for non-LLNA method:

The current endpoint has been fulfill with current available data. The current available data was made using a non-LLNA method. In addition and due to the available data rubisdium salts are not considered as a skin sensitizer. Therefore, no other test will be conducted for this endpoint.

Test material

Test material information

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 "99%"

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: albino

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Weight at study initiation: 300 - 400 g

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal

Vehicle:

water

Concentration / amount:

0.1 mL vol of 0.1% solutionof the test compound

Day(s)/duration:

2 weeks

Challenge

Route:

other: not specified

Concentration / amount:

0.1 ml of the test compound

Day(s)/duration:

after 2 weeks after first injection and then, skin examined at 24, 48 and 72 hours.

Adequacy of challenge:

not specified

No. of animals per dose:

control: 5 males
test group: 10 males

Details on study design:

RANGE FINDING TESTS: no data

MAIN STUDY
Fifteen young adult male albino guinea pigs weighing between 300 and 400 grams were used. Five animals served as a control group and 10 animals were assigned to the test group. The backs of the animals were clipped free of hair and the clipping repeated at various intervals during the study. The test materials, 0.1 ml (0.1 %), were injected intradermally to separate skin sites of the animals three times weekly for a total of nine treatments. The five control animals were treated in a manner identical to the test group but using the solvent, distilled water, as a control material. Twenty-four hours following each injection the reaction was measured for size. The animals in both the test and control groups were rested for a two-week period following the ninth injection. At the end of the two-week rest period a challenge dose of 0.1 ml was administered
to both the test and control animals in the same manner as before. Test sites were examined and reactions recorded at 24, 48 and 72 hours.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

0.1 mLof test compound

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

0.1 mL of the test compound

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Results 3

Key result

Reading:

1st reading

Hours after challenge:

72

Group:

test chemical

Dose level:

1 mL of the test compound

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

If the response to the challenge injection is greater in terms of intensity or local inflammatory response than to tbe sensitizing doses, or the numher of animals responding is substantially greater, then the material is considered to be a skin sensitizer.

There was no evidence of erythema, swelling or dicolorartion of the test sites after each of the nine sensitizing cutaneous injections or after the challenge dose. These results indicate that rubidium iodide did not induce cutaneous sensitisation in guinea pigs in any of the 10 test animals. On this basis the results of these guinea pig study indicate that rubidium iodide is a non-sensitizer.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Rubidium iodide did not induce cutaneous sensitisation in guinea pigs.

Executive summary:

In a dermal sensitisation study with rubidium iodide (0.1 %) in water, young adult male albino guinea pigs (in total 15 animals) were tested using the method of Landsteiner and Jacobs (1935). The test compound was administered intradermally three times a week, for a total of nine treatments. Following a two-week period with no further injections a challenge of 0.1% was administered the same way. There was no evidence of erythema, swelling or dicolorartion of the test sites after each of the nine sensitizing cutaneous injections or after the challenge dose. The results of these guinea pig study indicate thatrubidium iodide is a non-sensitizer.