Caesium iodide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Study period:

2013-04-30

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

other: expert statement

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Expert statement according to ECHA Guidance 2008, chapter R.7c

Test material

Test material information

Constituent 1

Reference substance name:

Caesium iodide

EC Number:

232-145-2

EC Name:

Caesium iodide

Cas Number:

7789-17-5

Molecular formula:

CsI

IUPAC Name:

caesium iodide

Test material form:

solid: crystalline

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

ORAL ABSORPTION:
Upon oral intake, cesium iodide will reach the stomach and form the respective Cs+ and I- ions. Based on the reduced molecular weight the absorption of the the ion through the walls of the gastrointestinal (GI) tract is likely to occur via passive diffusion. Moreover, for the cesium ion absorption is facilitated by transport through potassium channels and activation of the sodium pump (Cecchi et al., 1987; Edwards, 1982). Another common route of absorption, namely crossing of the gut epithelial by passing through aqueous pores or through membranes by bulk transport of water, is also likely due to the good water solubility and their molecular weight below 200 g/mol of the respective ions.

With regard to toxicological data, a study in rats revealed an LD50 value above 2000 mg/kg bw (Johnson et al., 1975).
Interestingly, in a 14 day dose range finder study the related analogue substance cesium hydroxide monohydrate caused changes in haematology and clinical chemistry parameters. Furthermore, a disturbance in the body weight development was observed.
In a subacute 28 day study the analogue cesium hydroxide monohydrate caused a slight depression in the body weight development and changes in serum potassium levels for male animals. Moreover, changes in serum potassium and creatinine concentrations and reduced kidney weights were noted for the female animals.
The results obtained from a subchronic 90 day repeated dose study with analogue substance cesium hydroxide monohydrate provided further evidence for systemic absorption. Here, high concentrations caused changes in haematology parameters and adverse effects to the male’s reproductive organs.

According to literature it is generally accepted that soluble cesium compounds are rapidly absorbed through the walls of the GI tract of humans (Henrichs et al., 1989; Iinuma et al., 1965). Further, animal studies on rats and guinea pigs support these findings (Talbot et a., 1993; Stara, 1965).
It is known from literature that the oral ingestion of water soluble iodide salts typically results in almost 100 % absorption (summarised in ATSDR, 2004).

Taken together, due to its physico-chemical properties and the observed systemic toxicity at least at high concentrations of cesium compounds cesium iodide more precisely the two respective ions will be well absorbed within the GI tract and become bioavailable following oral administration. This estimation is confirmed by literature data.

DERMAL ABSORPTION:
The physico-chemical properties of the parent substance and the respective ions do not favour dermal absorption. The surface tension of an aqueous solution (1 g/L) lies above 10 mN/m. This and the ionic nature of the inorganic salt will hinder dermal uptake.
Pendic and Milivojevic (1966) conducted a dermal absorption study on the analogue substance cesium chloride in rats. In this study it was determined that only a minor fraction (approximately 3 %) of radiolabeled cesium chloride applied to a skin surface of several cm2 was absorbed within 6 hours into the systemic circulation.
Based on the available literature the dermal absorption of iodine is estimated to be 1 % (summarised in ATSDR, 2004).
Consequently, acute systemic dermal toxicity test with cesium iodide on rats did not reveal that toxicological relevant amounts were absorbed into the systemic circulation. Here, no systemic effects were observed and the LD50 was determined to be greater than 2000 mg/kg bw (limit dose).

Taken together, based on its physico-chemical properties and absence of toxicity in an acute dermal toxicity study very limited absorption into the systemic circulation is expected after dermal application. Literature data support this estimation.

RESPIRATORY ABSORPTION:
Considering the very low vapour pressure, the resulting low volatility and the fact that the chemical exist as a crystalline solid at room temperature with particle sizes well above 100 μm it is unlike that the substance will be inhaled either in vapour form or as dust particles under use conditions.

Details on distribution in tissues:

Once absorbed into the blood stream, the cesium ion is readily distributed throughout the body. The water solubility and the reduced molecular weight due to ionization favour the distribution. Within the body, the cesium cation behaves in a similar manner as the potassium cation (Rundo 1964; Rundo et al., 1963). In order to gain entrance to the interior part of body cells, both alkali metals compete with each other for the transport through potassium channels and activation of the sodium pump (Cecchi et al., 1987; Edwards 1982). Miller (1964) evaluated the distribution profile of cesium while examining two workers who were accidentally exposed to the radioactive form of this element (137Cs) via the inhalation route. This study showed that cesium was quite uniformly distributed to the whole body (head, chest, upper abdomen, lower abdomen, thighs, legs, and feet). Furthermore, it was shown that bioaccumulation to a particular body tissue is unlikely. The described uniform distribution within the whole body was also observed in several animal studies (Furchner et al., 1964; Boecker 1969a and 1969b; Stara 1965). Interestingly, a study conducted by Vandecasteele et al. (1989), with adult sheep showed that cesium was able two cross the placenta and, furthermore, was detectable in the breast milk.
Iodide is actively transported into the thyroid follicle by the sodium iodine symporter, thus, 70 – 90 % of the iodine in the body accumulates in the thyroid gland (summarised in ATSDR, 2004).

Taken together, based on the physico-chemical properties the respective ions of cesium ions are readily distributed throughout the body. This is confirmed by the presence of target organs in subacute and subchronic studies (see field "Details on absorption") and literature data. In addition, iodide is mainly actively transported into the thyroid gland.

Details on excretion:

Urinary excretion is the major route of elimination of bioavailabe cesium from the human body. This route is favoured by the relatively low molecular weight of the ions (< 300 g/mol) and the water solubility. Only a very limited fraction is excreted with the faeces. After an initial relatively fast excretion rate, remaining amounts of the element are eliminated in a rather slow manner from the human body with average half times often exceeding 12 weeks, depending on age, sex and route of administration (Henrichs et al., 1989; Richmond et al., 1962). The element is relatively uniformly eliminated without selectively accumulating in certain tissues (Boecker 1969b).
Above 97 % of the absorbed iodide is urinary excreted. Minor amounts are eliminated via breast milk, salivia, sweat, tears and exhaled air. The elimination of iodide in breast milk is well documented. The whole body elimination half-time of absorbed iodine has been estimated to be approximately 31 days (summarised in ATSDR, 2004).

Taken together, considering the physico-chemical properties and the available literature cesium iodide is mainly urinary excreted.

Metabolite characterisation studies

Details on metabolites:

Due to the physico-chemical properties and according to available literature (Miller 1964, Boecker 1969b) it is not likely that cesium ions will undergo further enzymatic biotransformation processes or will reveal an accumulation potential.
Iodide is actively transported into the thyroid follicle by the sodium iodine symporter and then oxidised to molecular iodine. Thus, 70 – 90 % of the iodine in the body accumulates in the thyroid gland, which produces iodine containing thyroid hormones (summarised in ATSDR, 2004).

Any other information on results incl. tables

References

 

Agency for Toxic Sunstances and Disease Registry (ATSDR) Toxicological Profile for Iodine. U.S. Department of Health and Human Services

 

Boecker BB. (1969a) Comparison of137Cs metabolism in the beagle dog following inhalation and intravenous injection. Health Physics 16(6):785-788.

 

Boecker BB. (1969b) The metabolism of137Cs inhaled as137CsCl by the beagle dog. Proceedings of the Society Experimental Biology and Medicine 130(3):966-971.

 

Cecchi X., Wolff D., Alvarez O., Latorre, R. (1987) Mechanisms of Cs+ blockade in a Ca2+ -activated K+ channel from smooth muscle. Biophysical Journal 52:707-716.

 

ECHA (2008) Guidance on information requirements and chemical safety assessment, Chapter R.7c.: Endpoint specific guidance.

 

Edwards C. (1982) The selectivity of ion channels in nerve and muscle. Neuroscience 7:1335-1366.

 

Furchner JE., Trafton GA., Richmond CR.(1964) Distribution of cesium137 after chronic exposure in dogs and mice. Proceedings of the Society Experimental Biology and Medicine 116:375-378.

 

Henrichs K., Paretzke HG., Voigt G,.Berg D (1989) Measurements of Cs absorption and retention in man. Health Physics 57(4):571-578.

 

Iinuma T., Nagai T., Ishihara T. (1965) Cesium turnover in man following single administration of132Cs: Whole body retention and excretion pattern. Journal of Radiation Research 6:73-81.

 

Johnson G.T., Lewis R.T., Perone V.P. (1975) Acute Toxicity studies of cesium and rubidium compounds. Toxicology and applied pharmacology 32, 239-245.

 

Miller CE. (1964) Retention and distribution of 137Cs after accidental inhalation. Health Physics 10:10651070.

 

Pendic B., Milivojevic K. (1966) Contamination interne au137Cs par voie transcutanée et effet des moyens de décontamination et de protection sur la résorption transcutanée de ce radionuclide. Health Physics 12:1829-1830.

 

Richmond CR., Furchner JE., Langham WH.(1962) Long-term retention of radiocesium by man. Health Physics 8:201-205.

 

Rundo J. (1964) A survey of the metabolism of caesium in man. British Journal of Radiology 37:108-114.

 

Rundo J., Mason JI., Newton D., Taylor BT. (1963) Biological half-life of caesium in man in acute chronic exposure. Nature 200:188-189.

 

Stara JF. (1965) Tissue distribution and excretion of cesium-137 in the guinea pig after administration by three different routes. Health Physics 11:1195-1202.

 

Talbot RJ, Newton D, Segal MG. (1993) Gastrointestinal absorption by rats of137Cs and 90Sr from U3O8 fuel particles: Implications for radiation doses to man after a nuclear accident.

Radiation Protection Dosimetry 50(1):39-43.

 

Vandecasteele CM, Van Hees M., Culot JP., Vankerkorn J. (1989) Radiocaesium metabolism in pregnant ewes and their progeny. Science of the Total Environment 85:213-223.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
In accordance with the Guidance on Information Requirements and Chemical Saftey Assessment, chapter R.7c (ECHA, 2008) the profile on basic toxicokinetics of cesium iodide was derived from physico-chemical data as well as from toxicological data of cesium iodide and structurally related cesium salts.

Due to its physico-chemical properties and the observed systemic toxicity at least at high concentrations of cesium compounds cesium iodide more precisely the two respective ions will be well absorbed within the GI tract and become bioavailable following oral administration. This estimation is confirmed by literature data.

Based on its physico-chemical properties and absence of toxicity in an acute dermal toxicity study very limited absorption into the systemic circulation is expected after dermal application. Literature data support this estimation.

Considering the very low vapour pressure, the resulting low volatility and the fact that the chemical exist as a crystalline solid at room temperature with particle sizes well above 100 μm it is unlike that the substance will be inhaled either in vapour form or as dust particles under use conditions.

Based on the physico-chemical properties the respective ions of cesium ions are readily distributed throughout the body. This is confirmed by the presence of target organs in subacute and subchronic studies and literature data. In addition, iodide is mainly actively transported into the thyroid gland.

Due to the physico-chemical properties and according to available literature it is not likely that cesium ions will undergo further enzymatic biotransformation processes or will reveal an accumulation potential.
Iodide is actively transported into the thyroid follicle by the sodium iodine symporter and then oxidised to molecular iodine. Thus, 70 – 90 % of the iodine in the body accumulates in the thyroid gland, which produces iodine containing thyroid hormones.

Considering the physico-chemical properties and the available literature cesium iodide is mainly urinary excreted.