Aluminate(1-), tetrafluoro-, cesium (1:1), (T-4)-

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.35 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):

75

Modified dose descriptor starting point:

NOAEC

Value:

26.4 mg/m³

Explanation for the modification of the dose descriptor starting point:

8 h exposure time, extrapolation from 50% bioavailability oral to 100% bioavailability inhalation, no inhalation study available.

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

not for concentrations

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

for worker

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

135 mg/m³

Most sensitive endpoint:

acute toxicity

Route of original study:

By inhalation

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

12.5

Modified dose descriptor starting point:

NOAEC

Value:

1 688 mg/m³

AF for dose response relationship:

1

AF for interspecies differences (allometric scaling):

1

AF for other interspecies differences:

2.5

AF for intraspecies differences:

5

AF for the quality of the whole database:

1

AF for remaining uncertainties:

1

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

6.25 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):

300

Modified dose descriptor starting point:

NOAEL

Value:

1 875 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

8 h exposure time, no dermal study available

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

rat to human

AF for other interspecies differences:

2.5

Justification:

default factor for remaining differences

AF for intraspecies differences:

5

Justification:

for worker

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not 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

According to the REACH Guidance on information requirements and chemical safety assessment, a leading DN(M)EL needs to be derived for every relevant human population and every relevant route, duration and frequency of exposure, if feasible.

 

Short-term toxicity

According to the REACH guideline (R8, Appendix R 8-8), a DNEL for acute toxicity should be derived if an acute toxicity hazard (leading to C&L) has been identified and there is a potential risk for high peak exposures. The substance is classified for acute inhalation toxicity. For short term exposure to cesium tetrafluoroaluminate, a DNEL has been derived based on the results of an acute inhalation study according to the REACH guidance.

No data are available concerning local effects after repeated dermal contact with cesium tetrafluoroaluminate. Based on the read-across from cesium fluoro aluminate complex, the substance is not considered to be irritating or sensitizing to the skin, while it is considered to be corrosive for eyes. Therefore, no local dermal DNELs need to be derived.

 

Long-term toxicity

The key study for DNEL derivation was identified as a repeated dose oral study according to OECD 407 (Rijcken Pels, 1999) where a NOAEL of 30 mg/kg bw/day was derived. The DNELs for chronic systemic toxicity for the inhalation and dermal route are derived via route-to-route extrapolation based on the repeated dose oral toxicity study.

In the absence of substance specific quantitative data on absorption, 100% absorption is assumed for the inhalation and 50% for the oral route. For the dernal route, 1.6% absorption is assumed.

Worker DNELs

Long-term inhalation, systemic effects

As inhalation repeated dose toxicity studies with cesium tetrafluoroalulminate are not available, route to route extrapolation was applied to derive a DNEL for the inhalation route, based on the results of an oral 28-day repeated dose study with the read-across candidate cesium fluoro aluminate complex in rat (Rijcken Pels, 1999) where an NOAEL of 30 mg/kg bw/day was derived.

 

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 30 mg/kg bw/day	Exposure of rats at concentrations up to 30 mg/kg bw/day did not induce clinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters. Based on the findings in the stomach, kidneys and spleen in the mid and high dose animals, a dose of 30 mg/kg bw/day was considered as NOAEL.
Step 2) Modification of starting point	2      0.38 m^3/kg bw           6.7 m^3/10 m^3	The REACH Guidance on information requirements and chemical safety assessment (R.8.4.2) prescribes a default factor of 2 in case of oral to inhalation extrapolation.   Standard respiratory volume of a rat, corrected for 8 h exposure, as proposed in the REACH Guidance on information requirements and chemical safety assessment (R.8.4.2).   Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.
Modified dose-descriptor	30 x (1/0.38) x (1/2) x (6.7/10) = 26.4 mg/m^3
Step 3) Assessment factors
Interspecies	2.5	No factor for allometric scaling is needed in case of inhalation exposure.A default factor of 2.5 for remaining uncertainties is used.
Intraspecies	5	Default AF for workers
Exposure duration	6	Extrapolation to chronic exposure based on a sub-acute toxicity study
Dose response	1
Quality of database	1
DNEL	Value
	26.4 / (2.5 x 5 x 6 x 1 x 1) = 0.35 mg/m^3

Short-term – inhalation, systemic effects

Approach according to REACH guidance

Based on the available acute inhalation toxicity study with cesium tetrafluoroaluminate in rats (Van Huygevoort, 2013).

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEC: 1000 mg/m^3	No deaths occurred and no abnormalities were found at macroscopic examination. Therefore, 1000 mg/m^3is interpreted as a NOAEC.
Step 2) Modification of starting point	3√(1000^3x 16)                       6.7/10	In the REACH guidance (R.8, Appendix R. 8-8), it is mentioned: ‘If a DNEL for acute toxicity needs to be established, this should be derived only for a specified fraction of the daily exposure duration (usually 15 minutes)’. The most appropriate approach is the modified Haber’s law (C^n* t = k). For extrapolation from longer to shorter durations a default value of n=3 should be used.   Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m^3/10 m^3).
Step 3) Assessment factors
Interspecies	2.5	For inhalation studies only a factor 2.5 is used, and no correction is made for differences in body size, because extrapolation is based on toxicological equivalence of a concentration of a chemical in the air of experimental animals and humans; animals and humans breathe at a rate depending on their caloric requirements.
Intraspecies	5	Default AF for workers
Exposure duration	1
Dose response	1
Quality of database	1
Step 4) Calculate DNEL	^3√(1000^3x 16) x (6.7/10) / (2.5 x 5 x 1 x 1 x 1) = 135 mg/m^3

 

Long-term dermal, systemic effects

As dermal repeated dose toxicity studies with cesium tetrafluoroaluminate are not available, route to route extrapolation was applied to derive a DNEL for the dermal route, based on the results of an oral 28-day repeated dose study with the read-across candidate cesium fluoro aluminate complex in rat (Rijcken Pels, 1999) where an NOAEL of 30 mg/kg bw/day was derived.

 

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 30 mg/kg bw/day	Exposure of rats at concentrations up to 30 mg/kg bw/day did not induceclinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the findings in the stomach, kidneys and spleen in the mid and high dose animals, a dose of 30 mg/kg bw/day was considered as NOAEL.
Step 2) Modification of starting point	100/1.6	Conversion into dermal NAEL (in mg/kg bw/day) assuming 100% oral absorption and 1.6% dermal absorption for cesium tetrafluoroaluminate.
Modified dose-descriptor	30 x (100/1.6) = 1875 mg/kg bw/day
Step 3) Assessment factors
Interspecies	4 x 2.5	Assessment factor for allometric scaling and remaining uncertainties.
Intraspecies	5	Default AF for workers
Exposure duration	6	Extrapolation to chronic exposure based on a sub-acute toxicity study
Dose response	1
Quality of database	1
DNEL	Value
	1875 / (4 x 2.5 x 5 x 6 x 1 x 1) = 6.25 mg/kg bw/day

 

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:

DNEL (Derived No Effect Level)

Value:

0.05 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):

600

Modified dose descriptor starting point:

NOAEL

Value:

30 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no route to route extrapolation performed

AF for dose response relationship:

1

Justification:

not required, starting point is NOAEL

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

extrapolation rat to human

AF for other interspecies differences:

2.5

Justification:

remaining differences

AF for intraspecies differences:

10

Justification:

general population

AF for the quality of the whole database:

1

Justification:

not required

AF for remaining uncertainties:

1

Justification:

not required

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

General population DNELs

As there is no consumer use for cesium tetrafluoroaluminate, no inhalation and dermal DNELs for the general population were calculated. However, the deposition of cesium fluoroaluminate in the environment may contribute to the total cesium and fluoride intake of the general public, therefore, a long-term oral DNEL for the general population was calculated. No route-to-route extrapolation had to be performed since the DNEL has been derived from a NOAEL observed in an oral 28-day repeated dose study with the read-across candidate cesium fluoro aluminate complex in rat (Rijcken Pels, 1999).

Long-term – oral, systemic effects (based on sub-acute oral toxicity study with rats)

Description	Value	Remark
Step 1) Relevant dose-descriptor	NOAEL: 30 mg/kg bw/day	Exposure of rats at concentrations up to 30 mg/kg bw/day did not induceclinical abnormalities, differences in food consumption and body weight, and changes in haematology or clinical chemistry parameters.Based on the findings in the stomach, kidneys and spleen in the mid and high dose animals, a dose of 30 mg/kg bw/day was considered as NOAEL.
Step 2) Modification of starting point	-
Step 3) Assessment factors
Interspecies	4 x 2.5	Default assessment factors for allometric scaling and remaining interspecies differences.
Intraspecies	10	Default assessment factor for general population
Exposure duration	6	Extrapolation to chronic exposure based on a sub-acute toxicity study.
Dose response	1
Quality of database	1
DNEL	Value
	30 / (4 x 2.5 x 10 x 6 x 1 x 1) = 30 / 600 = 0.05 mg/kg bw/day