Caesium fluoride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.46 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):

37.5

Dose descriptor starting point:

LOAEL

Value:

13.9

Modified dose descriptor starting point:

LOAEC

Value:

17.2 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:

3

Justification:

The assessment factor was used for extrapolation from LOAEC to NOAEC.

AF for differences in duration of exposure:

1

Justification:

No time extrapolation factor is needed since a chronic toxicity study is available.

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:

5.2 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):

37.5

Dose descriptor starting point:

LOAEL

Value:

13.9 mg/kg bw/day

Modified dose descriptor starting point:

LOAEL

Value:

139 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

The physicochemical properties of the parent substance and its respective ions, being charged, do not favour dermal absorption. The ionic nature of the inorganic salt will hinder dermal uptake. Pendic and Milivojevic (1966) conducted a dermal absorption study on the structural analogous substance cesium chloride (CsCl) in rats. In this study it was determined that only a minor fraction (approximately 3 %) of radiolabeled CsCl applied to a skin surface of several cm² was absorbed within 6 hours and became systemically available. It is therefore assumed that the test items absorption corresponds to 10 % of the oral uptake.

AF for dose response relationship:

3

Justification:

The assessment factor was used for extrapolation from LOAEL to NOAEL.

AF for differences in duration of exposure:

1

Justification:

No time extrapolation factor is needed since a chronic toxicity study is available.

AF for interspecies differences (allometric scaling):

1

Justification:

Metabolism of cesium fluoride 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:

medium hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

General

No respective experimental systemic data for cesium fluoride are available. Consequently, read-across was applied using study results from cesium hydroxide monohydrate, cesium chloride and sodium fluoride to cover both ions of the target substance. Please refer to IUCLID section 13 for read-across justification. The DNEL derivation is based on the LOAEL for sodium fluoride as worst case.

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

Long term exposure- systemic effect

Inhalation exposure

A subchronic repeated dose toxicity test with cesium fluoride is not available. Consequently, read-across was applied using study results from sodium fluoride (1990).

In order to derive the worker DNEL (long-term inhalation exposure), the LOAEL assessed in the chronic repeated dose oral toxicity study with the structural analogue sodium fluoride was used (NOAEL 3.75 mg/kg bw/day). The DNEL derivation is based on the calculated LOAEL for cesium fluoride of 13.9 mg/kg bw/day. 

 

Correction of the dose descriptor

Oral NOAEL: 13.9 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 = 13.9 mg/kg bw/d x 1/0.38 m³ x 0.5 x 0.67 m³ x 1.4 = 17.2 mg/m³.

 

Calculation of the worker DNEL

Corrected inhalatory NOAEC for worker: 17.2 mg/m³

Assessment factor for exposure duration (chronic): 1

Assessment factor for intraspecies differences (worker): 5

Assessment factor for other interspecies differences: 2.5

Assessment factor for dose-response relationship: 3

Worker DNEL (inhalation exposure) = 17.2 mg/m³ / (1 x 5 x 2.5 x 3) = 17.2 / 37.5 = 0.46 mg/m³

 

 

 

Dermal exposure

In order to derive the worker DNEL (long-term dermal exposure), the LOAEL assessed in the chronic repeated dose oral toxicity study was used. The LOAEL of the test item sodium fluoride was 3.75 mg/kg bw/day. The DNEL derivation is based on the calculated LOAEL for cesium fluoride of 13.9 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: 139 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 = 139 mg/kg bw/d x 1.4 = 195 mg/kg bw/d

 

Calculation of worker DNEL

Corrected dermal NOAEL for worker: 195 mg/kg bw/d

Assessment factor for exposure duration (chronic): 1

Allometric scaling factor (rat to human): 1

Assessment factor for intraspecies differences (worker): 5

Assessment factor for other interspecies differences: 2.5

Assessment factor for dose-response relationship: 3

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

Worker DNEL (dermal exposure) = 195 mg/kg bw/day / (1 x 1 x 2.5 x 5 x 3) = 195 / 37.5 = 5.2 mg/kg bw/d

 

Acute/ short term exposure- systemic effect

Inhalation: There is no indication for acute systemic toxicity of cesium fluoride. 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 fluoride. 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 fluoride 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. 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 in vitro skin irritation study according to OECD 439 concluded not irritant for cesium fluoride. However it was classified as skin irritating based on an in vivo skin corrosion study with the source substance sodium fluoride for precautionary reasons. Thus, qualitative approach was applied to hazard and risk assessment with relevant RMM (ECHA CSA R.8, 2012).

Eye irritation: Based on in vivo eye irritation studies with aqueous sodium fluoride solution, cesium fluoride is classified for serious eye damage according to Regulation (EC) No 1272/2008 (CLP/GHS). The mechanism of effect is direct pH reactivity because sodium fluoride exhibits an alkaline pH of around 10. Although cesium fluoride shows a neutral pH in aqueous solution a qualitative approach (medium hazard) 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