Caesium hydroxide

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.31 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

15

Modified dose descriptor starting point:

NOAEC

Value:

19.67 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:

3

Justification:

Intraspecies differences of workers are considered to be fully covered by the selected factor according to ECETOC Technical Report No. 110.

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:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1 mg/m³

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.72 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance and ECETOC Technical Report No. 110

Overall assessment factor (AF):

60

Modified dose descriptor starting point:

NOAEL

Value:

223.1 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):

4

Justification:

The default allometric scaling factor for the differences between rats and humans is used.

AF for other interspecies differences:

2.5

Justification:

Default factor according to ECHA guidance document.

AF for intraspecies differences:

3

Justification:

An intraspecies difference factor of 3 for workers is considered to be sufficient (ECETOC Technical Report No. 110).

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:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

General

The DNEL derivation is based on the calculated NOAEL for cesium hydroxide anhydrous. DNEL derivation for the test item is performed under consideration of the recommendations of ECHA REACH Guidance (2010) and ECETOC (2010). In view of the data used for evaluation, the "quality of whole database factors" and "dose-response factors" are considered to amount each to a value of 1.

 

Long term exposure- systemic effect

Inhalation exposure

In order to derive the worker DNEL (long-term inhalation 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 hydroxide anhydrous of 22.31 mg/kg bw/day.

 

Correction of the dose descriptor

Oral NOAEL: 22.31 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]

The oral NOAEL= 22.31 mg/kg bw/ day is converted in an inhalation NOAEC= 19.67 mg/ m3.

 

Calculation of the worker DNEL

Corrected inhalatory NOAEC for worker: 19.67 mg/ m3

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

Assessment factor for intraspecies differences (worker): 3 

Assessment factor for other interspecies differences: 2.5

Worker DNEL (inhalation exposure) = 19.67 mg/m3/ (1 x 2 x 1 x 3 x 2.5 x 1 x 1) = 19.67 / 15 = 1.31 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 hydroxide anhydrous of 22.31 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: 223.31 mg/kg bw/day (NOAEL x 10; assuming 10 % dermal absorption)

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

Allometric scaling factor (rat to human): 4

Assessment factor for other interspecies differences: 2.5

Assessment factor for intraspecies differences (worker): 3 

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

Worker DNEL (dermal exposure) = 223.1 mg/kg bw/day / (1 x 2 x 4 x 2.5 x 3 x 1 x 1) = 223.1 / 60 = 3.72 mg/kg bw/day

 

Acute/ short term exposure- systemic effect

Inhalation: There is no indication for acute systemic toxicity after inhalative exposure to cesium hydroxide monohydrate and therewith for cesium hydroxide anhydrous. Both substances are not classified for inhalation toxicity. Also no peak exposure is expected. Therefore no DNEL was derived.

Dermal: No acute dermal study was available with cesium hydroxide monohydrate or cesium hydroxide anhydrous. LD50 and LD0 values of > 2000 mg/kg bw and 2000 mg/kg bw, respectively were obtained in an animal study (EU method B.2, OECD 402) with cesium nitrate and cesium iodide. The results were adapted by a read-across approach to cesium hydroxide. The results were adapted by a read-across approach to cesium hydroxide anhydrous 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: There is no indication for acute local toxicity after inhalation exposure to cesium hydroxide monohydrate and therewith also cesium hydroxide anhydrous. They are classified as corrosive to skin and eye (R35) according to Directive 67/548/EEC (DSD) and as corrosive cat. 1A (H314) according to the Regulation (EC) No 1272/2008 (CLP).They may therefore also react with the mucosa of the respiratory tract, due to a strong basic character (based on the OH- content of the salt). According to the VCI expert statement (Jan 2010) a conservative approach for corrosive substances is applied using a threshold value of 1 mg/m3.

 

Skin irritation: cesium hydroxide monohydrate and therewith also cesium hydroxide anhydrous are classified as corrosive to the skin (R35) according to Directive 67/548/EEC (DSD) and as skin corrosive cat. 1A (H314) according to the Regulation (EC) No 1272/2008 (CLP).No acute and long term local DNEL was derived but a qualitative approach was applied to exposure and risk assessment with relevant RMM (ECHA CSR R.8, 2010).

 

Eye irritation: cesium hydroxide monohydrate and therewith also cesium hydroxide anhydrous are corrosive to the skin and consequently severely damaging to the eye due to a strong basic character (based on the OH- content of the salt). They are classified as corrosive to the eye (R35) according to Directive 67/548/EEC (DSD) and as eye damaging (H314) according to the Regulation (EC) No 1272/2008 (CLP). No acute and long term local 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.

according to Annex VI of Regulation EC 1272/2008 (CLP).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General population is not intended to be exposed to cesium hydroxide monohydrate and therewith cesium hydroxide anhydrous via inhalation, dermal or oral route. Therefore, no DNEL (long-term, inhalation, dermal, oral exposure) is derived for general population.