Caesium carbonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.2 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEL

Value:

24.3 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

29.9 mg/m³

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on the repeated exposure by inhalation. A conservative approach is used assuming a 50 % absorption rate via the oral route (end route) as compared to the inhalation route (starting route).

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Respiratory interspecies differences are fully covered by the factors used for route to route extrapolation.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

5

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further assessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

13.6 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

25

Dose descriptor starting point:

NOAEL

Value:

24.3 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

340.2 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

There are no relevant experimental data on repeated exposure by dermal absorption. Based on the physiochemical properties it is assumed that the test items absorption corresponds to 10 % of the oral uptake.

AF for dose response relationship:

1

Justification:

The dose response relationship is considered unremarkable, therefore no additional factor is used.

AF for differences in duration of exposure:

2

Justification:

The default extrapolation factor for exposure duration is used: subchronic (starting point) to chronic (end point).

AF for interspecies differences (allometric scaling):

1

Justification:

Metabolism of cesium carbonate as an inorganic salt can be excluded. There are no reasons to assume that this behaviour which is based on the physico-chemical properties of the substance will be different between rats and humans. Therefore, it is considered to be justified to apply substance-specific assessment factors accounting for a correction for differences in metabolic rate of 1 instead of using the respective default factor of 4.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

5

Justification:

Default factor according to ECHA guidance document.

AF for the quality of the whole database:

1

Justification:

The quality of the whole data base is considered to be sufficient and uncritical.

AF for remaining uncertainties:

1

Justification:

The approach used for DNEL derivation is conservative. No further aassessment factors are required.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

General

No experimental systemic toxicity data for cesium carbonate are available. Consequently, read-across was applied using study results obtained in subchronic toxicity studies with cesium hydroxide monohydrate and cesium chloride. Please refer to IUCLID section 13 for read-across justification. The DNEL derivation is based on the calculated NOAEL for cesium carbonate taken into account both studies.

DNEL derivation is performed under consideration of the recommendations of ECHA REACH Guidance (2010).

 

Long term exposure- systemic effect

A subchronic repeated dose toxicity test with cesium carbonate is not available. Consequently, read-across was applied using study results obtained with cesium hydroxide monohydrate (2013) and cesium chloride (2016). Considering the different dose regimens, the NOAEL observed for cesium hydroxide was chosen as a starting point. For further information please refer to IUCLID section 7.5.1.

 

Inhalation exposure

In order to derive the worker DNEL (long-term inhalation exposure), the NOAEL derived in the 90-day repeated dose oral toxicity study with the structural analogue cesium hydroxide monohydrate was used (NOAEL 25 mg/kg bw/day). The DNEL derivation is based on the calculated NOAEL for cesium carbonate of 24.3 mg/kg bw/day taken the molecular weight and Cs content of both salts into account. 

 

Correction of the dose descriptor

Oral NOAEL: 24.3 mg/kg bw/day

sRV(rat): 0.38 m³/kg bw (8 hours) [standard respiratory volume of the rat]

ABS oral (rat) / ABS inhalation (human): 0.5 [ratio of oral absorption in the rat to inhalative absorption in the human]

sRV (human) / wRV (human): 6.7 m³/10 m³ = 0.67 m³ [ratio of human standard respiratory volume to worker respiratory volume]

Differences experimental/human exposure conditions: 1.4 [ratio of 7 d exposure of the rat to 5 d exposure of the human]

The inhalatory NOAEC = 24.3 mg/kg bw/d x 1/0.38 m³ x 0.5 x 0.67 m³ x 1.4 = 29.9 mg/m³.

 

Calculation of the worker DNEL

Corrected inhalatory NOAEC for worker: 29.9 mg/m³

Assessment factor for exposure duration (subchronic to chronic): 2

Assessment factor for intraspecies differences (worker): 5

Assessment factor for other interspecies differences: 2.5

Worker DNEL (inhalation exposure) = 29.9 mg/m³ / (2 x 5 x 2.5) = 29.9 / 25 = 1.2 mg/m³

 

 

 

Dermal exposure

In order to derive the worker DNEL (long-term dermal exposure), the NOAEL assessed in the key 90- day repeated dose oral toxicity study was used. The NOAEL of the test item cesium hydroxide monohydrate was 25 mg/kg bw/day. The DNEL derivation is based on the calculated NOAEL for cesium carbonate of 24.3 mg/kg bw/ day. Considering the appropriate assessment factors, the worker DNEL (long-term dermal exposure) is calculated as follows:

 

Correction of the dose descriptor

Dose descriptor of relevant study: 243 mg/kg bw/d (NOAEL x 10; assuming 10 % dermal absorption)

Differences experimental/human exposure conditions: 1.4 [ratio of 7 d exposure of the rat to 5 d exposure of the human]

The dermal NOAEL = 243 mg/kg bw/d x 1.4 = 340.2 mg/kg bw/d

 

Calculation of worker DNEL

Corrected dermal NOAEL for worker: 340.2 mg/kg bw/d

Assessment factor for exposure duration (subchronic to chronic): 2

Allometric scaling factor (rat to human): 1

Assessment factor for intraspecies differences (worker): 5

Assessment factor for other interspecies differences: 2.5

Taking the above mentioned assessment factors into account, the following worker DNEL is:

Worker DNEL (dermal exposure) = 340.2 mg/kg bw/day / (2 x 1 x 5 x 2.5) = 340.2 / 25 = 13.6 mg/kg bw/d

 

Acute/ short term exposure- systemic effect

Inhalation: There is no indication for acute systemic toxicity of cesium carbonate. The substance is not classified for inhalation toxicity. Also no peak exposure is expected and inhalation exposure is expected to be negligible. Therefore no DNEL is required.

Dermal: No acute dermal study was available with cesium carbonate. An LD50 value of > 2000 mg/kg bw was obtained in an animal study (EU method B.2, OECD 402) with cesium nitrate. The results were adapted by a read-across approach to cesium carbonate which was therefore not classified for acute systemic toxicity after dermal application. Therefore no DNEL was derived.

 

Acute and long term exposure- local effect

Respiratory irritation: The test item is classified for eye damage according Regulation (EC) No 1272/2008 (CLP). This implies that a potential damage to mucosal tissue may occur by inhalative exposure. Therefore, low hazard was applied for precautionary reasons because of its alkalinity in aqueous solutions. No threshold data could be derived from the respective studies/data. Thus, qualitative approach was applied to hazard and risk assessment with relevant RMM (ECHA CSA R.8, 2012).

Skin: The test item was not classified as skin irritating based on an in vitro skin corrosion study according to OECD 431 and an in vivo study with a 50 % solution according to OECD 404.

Eye irritation: Based on an eye corrosion/irritation study according to OECD 437 cesium carbonate is classified for serious eye damage according to Regulation (EC) No 1272/2008 (CLP/GHS). The mechanism of effect is direct pH reactivity because only alkaline cesium salts show irritating and corrosive potential. No DNEL was derived but a qualitative approach was applied to exposure and risk assessment with relevant RMM (ECHA CSR R.8, 2010).

 

References

- ECHA (2010). Guidance on information requirements and chemical safety assessment. Chapter R.8: Characterisation of dose [concentration]-response for human health. Version 2. ECHA-2010 -G-19–N.

- ECETOC (2010). Technical Report 110.Guidance on assessment factors to derive a DNEL.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population

General population is not intended to be exposed to cesium carbonate via inhalation, dermal or oral route. Therefore, no DNEL is derived for general population.