Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25.3 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
7.5
Dose descriptor starting point:
NOAEC
Value:
283 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
189.6 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
3
Justification:
Using a reduced factor of 3 (instead of 5) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.14 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
6
Dose descriptor:
NOAEC
Value:
1.21 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
1
Justification:
Humans are not considered more sensitive compared to rats and mice and an assessment factor of 1 is considered appropriate. Further explanations are given below in Additional information - Workers.
AF for intraspecies differences:
3
Justification:
Using a reduced factor of 3 (instead of 5) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25.3 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
7.5
Dose descriptor starting point:
NOAEC
Value:
283 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
3
Justification:
Using a reduced factor of 3 (instead of 5) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
140 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
42 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Conversion into dermal NOAEL assuming 100% oral absorption and 0.6% dermal absorption

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
Not applicable
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Detailed presentation of worker DNEL derivation

Acute – inhalation, systemic and local effects

Approach according to REACH guidance

Based on the available acute inhalation toxicity study in rats (TNO, 1999b).

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 283 mg/m3

As the acute inhalation toxicity studies (American Biogenics Corporation, 1985a,b) have some limitations regarding the derivation of an acute DNEL, i.e. the lack of a NOAEC from these studies which can be used as starting point, the sensory irritation study (TNO, 1999b) is used for the derivation of the acute DNEL. Abnormalities at necropsy consisted primarily of discoloured areas on the lungs to a varying extent at 592 and 604 mg/m3after 20 and 30 minutes exposure, respectively. Based on these findings, a NOAEC of 283 mg/m3was derived.

Step 2) Modification of starting point

-

 

 

 

 

 

 

 

 

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)’. As the NOAEC concerns 20/30 minutes single exposure no further modification of the starting point is performed.

 

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

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

3

Using a reduced factor of 3 (instead of 5) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.

Exposure duration

1

 

Dose response

1

 

Quality of database

1

 

Step 4) Calculate DNEL

283 x (6.7/10) / (2.5 x 3 x 1 x 1 x 1) = 25.3 mg/m3

 

Long-term – inhalation, local effects

Approach according to REACH guidance

Based on 90 days inhalation toxicity study in rats (TNO, 2004b)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 1.21 mg/m3

Presence of macrophages in the lungs was reported for 1.21 and 3.08 mg/m3(not at 0.32 mg/m3). The presence of these macrophages are considered a physiological response to the exposure and therefore not considered adverse as such. The increased lung weights (females) and increased numbers of neutrophils in blood (females) observed at the concentration of 3 mg/m3are considered adverse. No tissue reaction was present at any of the concentrations tested.

Step 2) Modification of starting point

-

 

 

 

 

 

6.7/10

According to the REACH guidance, time scaling is not appropriate when the toxic effect is mainly driven by the exposure concentration.

Correction for activity driven differences of respiratory volumes in workers compared to workers in rest (6.7 m3/10 m3).

Step 3) Assessment factors

 

 

Interspecies

1

In view of the exaggerated lung reaction of rats to dust inhalation, compared to the reaction of higher mammals (Snipes, 1989, 1996; Nikula et al, 1997, 2001), it is assumed that rats are more sensitive for the effects of aluminium potassium fluoride after inhalation exposure. In rats, significant macrophage activity is accompanied with inflammatory mediator release and inflammatory responses as neutrophils mobilisation (note that in the aluminium potassium fluoride study a tissue reaction was absent). Moreover, considering that retention of particles in higher mammals happens preferentially in the interstitium and considering that aluminium potassium fluoride is moderately (but slowly) soluble it may be assumed that long term retention of aluminium potassium fluoride particles in the interstitium will not occur. Aluminium potassium fluoride will dissociate, dilute and subsequently be transported in the fluids of the organism (Snipes, 1989, 1996; Nikula et al, 1997, 2001).

In conclusion, humans are not considered more sensitive compared to rats and mice and an assessment factor of 1 is considered appropriate.

Intraspecies

3

Using a reduced factor of 3 (instead of 5) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.

Exposure duration

2

Extrapolation from sub-chronic to chronic exposure

Dose response

1

 

Quality of database

1

 

Step 4) Calculate DNEL

(1.21 x 6.7/10) / (1 x 3 x 2 x 1 x 1) = 0.14 mg/m3

- Nikula KJ,KJ, Griffith WC, Mauderly JL (1997).Lung tissue responses and sites of particle retention differ between rats and cynomolgus monkeys exposed chronically to diesel exhaust and coal dust.Fundam Appl Toxicol.;37(1):37-53.

- Nikula KJ, Vallyathan V, Green FH, Hahn FF (2001).Influence of exposure concentration or dose on the distribution of particulate material in rat and human lungs.Environ Health Perspect.;109(4):311-8.

- Snipes MB (1989).Long-term retention and clearance of particles inhaled by mammalian species.Crit Rev Toxicol.;20(3):175-211.

- Snipes MB (1996). Current information on lung overload in nonrodent mammals: Contrast with rats. Inhal. Toxicol. 8:91-109.

Long-term – dermal, systemic effects

Approach according to REACH guidance

No dermal repeated dose toxicity studies are available for aluminium potassium fluoride. In the inhalation repeated dose toxicity studies no systemic effects were observed. Therefore a dermal long-term DNEL cannot be quantified using the inhalation route as starting point.

For the structural analogue of aluminium potassium fluoride, cryolite, effects on postnatal growth evidenced by significantly decreased pup body weights during lactation as well as pathologic gross findings in several organs of the pups resulted from dose levels without any significant parental toxicityin the two-generation study (oral route) (Pharmaco LSR, Inc., 1994). Because these effects occurred without any significant sign for parental toxicity it is considered to be indicative for a specific toxic potential of cryolite adverse to postnatal development. The respective NOAEL for these effects in this study was 42 mg cryolite/kg bw/day. This level will be used for derivation of the dermal DNEL of aluminium potassium fluoride.

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 42 mg/kg bw/day

Read-across using the two-generation study of the structural analogue cryolite: developmental toxic effects were observed at the dose level of 128 mg/kg bw/day and higher.

Step 2) Modification of starting point

100 / 0.6

 

 

Conversion into dermal NAEL (in mg/kg bw/day) assuming 100% oral absorption and 0.6% dermal absorption.

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Default assessment factor for allometric scaling and remaining uncertainties as taken from the REACH guidance.

Intraspecies

5

Default assessment factor taken from REACH.

Exposure duration

1

Not applicable

Dose response

1

 

Quality of database

1

 

Uncertainty factor (read-across)

1

Toxicokinetics

No additional factor is needed as in Step 2) substance-specific absorption figures are used.

 

Toxicodynamics

The main difference between cryolite and aluminium potassium fluoride in terms of constituting elements is the alkali metal cation, namely sodiumvs.potassium. Both these elements are essential constituents and two of the most abundant ions in all humans, as well as in all animal species. As systemic toxicity of both cryolite and aluminium potassium fluoride is primarily governed by accumulation of the fluoride formed upon hydrolysis of fluoroaluminate moieties, the same type of effects can be expected for the compounds. Based on the above, no differences in toxicodynamics are expected and therefore no additional factor is needed.

Step 4) Calculate DNEL

(42 x 100 / 0.6) / 4 x 2.5 x 5 x 1 x 1 x 1 x 1 = 140 mg/kg bw/day

 

No data are available concerning local effects after repeated dermal contact with aluminium potassium fluoride. The acute skin tests did not show local irritating or sensitising properties. From epidemiological data no observations on skin reactions from workers have been reported. In summary local effects by prolonged skin contact are not expected.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.9 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):
15
Dose descriptor starting point:
NOAEC
Value:
283 mg/m³
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:

As the NOAEC concerns 20/30 minutes single exposure no further modification of the starting point is performed.

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
6
Justification:
Using a reduced factor of 6 (instead of 10) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.03 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12
Dose descriptor:
NOAEC
Value:
1.21 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
1
Justification:
Humans are not considered more sensitive compared to rats and mice and an assessment factor of 1 is considered appropriate. Further explanations are given below in Additional information - General population
AF for intraspecies differences:
6
Justification:
Using a reduced factor of 6 (instead of 10) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
18.9 mg/m³
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor starting point:
NOAEC
Value:
283 mg/m³
AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEC
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling is not necessary for the inhalation route
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
6
Justification:
Using a reduced factor of 6 (instead of 10) is justified because the critical effect is a local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution, metabolism and elimination play no/a minor role.
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties identified

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
42 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
7 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Conversion into dermal NOAEL assuming 100% oral absorption and 0.6% dermal absorption

AF for dose response relationship:
1
Justification:
Not required, starting point is NOAEL
AF for differences in duration of exposure:
1
Justification:
Not applicable
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling (rat to human)
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
10
Justification:
Default factor for general population
AF for the quality of the whole database:
1
Justification:
Database of good quality
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties 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:
medium hazard (no threshold derived)

Additional information - General Population

Detailed presentation of general population DNEL derivation

Acute – inhalation, systemic and local effects

Approach according to REACH guidance

Based on the available acute inhalation toxicity study in rats (TNO, 1999b)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 283 mg/m3

As the acute inhalation toxicity studies (American Biogenics Corporation, 1985a,b) have some limitations regarding the derivation of an acute DNEL, i.e. the lack of a NOAEC from these studies which can be used as starting point, the sensory irritation study (TNO, 1999b) is used for the derivation of the acute DNEL. Abnormalities at necropsy consisted primarily of discoloured areas on the lungs to a varying extent at 592 and 604 mg/m3after 20 and 30 minutes exposure, respectively. Based on these findings, a NOAEC of 283 mg/m3was derived.

Step 2) Modification of starting point

-

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)’. As the NOAEC concerns 20/30 minutes single exposure no further modification of the starting point is performed.

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

6

Using a reduced factor is justified because the critical effect is a direct local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution and elimination play no/a minor role.

Exposure duration

1

 

Dose response

1

 

Quality of database

1

 

Step 4) Calculate DNEL

283 / (2.5 x 6 x 1 x 1 x 1) = 18.9 mg/m3

Long-term – inhalation, local effects

Approach according to REACH guidance

Based on 90 days inhalation toxicity study in rats (TNO, 2004b)

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 1.21 mg/m3

Presence of macrophages in the lungs was reported for 1.21 and 3.08 mg/m3(not at 0.32 mg/m3). The presence of these macrophages are considered a physiological response to the exposure and therefore not considered adverse as such. The increased lung weights (females) and increased numbers of neutrophils in blood (females) observed at the concentration of 3 mg/m3are considered adverse. No tissue reaction was present at any of the concentrations tested.

Step 2) Modification of starting point

6/24

Correction of exposure duration in study (6 hrs/day) to default population exposure (24 hrs/day).

Step 3) Assessment factors

 

 

Interspecies

1

In view of the exaggerated lung reaction of rats to dust inhalation, compared to the reaction of higher mammals (Snipes, 1989, 1996; Nikula et al, 1997, 2001), it is assumed that rats are more sensitive for the effects of aluminium potassium fluoride after inhalation exposure. In rats, significant macrophage activity is accompanied with inflammatory mediator release and inflammatory responses as neutrophils mobilisation (note that in the aluminium potassium fluoride study a tissue reaction was absent). Moreover, considering that retention of particles in higher mammals happens preferentially in the interstitium and considering that aluminium potassium fluoride is moderately (but slowly) soluble it may be assumed that long term retention of aluminium potassium fluoride particles in the interstitium will not occur. Aluminium potassium fluoride will dissociate, dilute and subsequently be transported in the fluids of the organism (Snipes, 1989, 1996; Nikula et al, 1997, 2001).

In conclusion, humans are not considered more sensitive compared to rats and mice and an assessment factor of 1 is considered appropriate.

Intraspecies

6

Using a reduced factor is justified because the critical effect is a direct local effect that is hardly if at all, mainly determined by toxicodynamics and kinetics. Absorption, distribution and elimination play no/a minor role.

Exposure duration

2

Extrapolation from sub-chronic to chronic exposure

Dose response

1

 

Quality of database

1

 

Step 4) Calculate DNEL

(1.21 x 6/24) / (1 x 6 x 2 x 1 x 1) = 0.03 mg/m3

- Nikula KJ,KJ, Griffith WC, Mauderly JL (1997).Lung tissue responses and sites of particle retention differ between rats and cynomolgus monkeys exposed chronically to diesel exhaust and coal dust.Fundam Appl Toxicol.;37(1):37-53.

- Nikula KJ, Vallyathan V, Green FH, Hahn FF (2001).Influence of exposure concentration or dose on the distribution of particulate material in rat and human lungs.Environ Health Perspect.;109(4):311-8.

- Snipes MB (1989).Long-term retention and clearance of particles inhaled by mammalian species.Crit Rev Toxicol.;20(3):175-211.

- Snipes MB (1996). Current information on lung overload in nonrodent mammals: Contrast with rats. Inhal. Toxicol. 8:91-109.

Long-term – dermal, systemic effects

Approach according to REACH guidance

No dermal repeated dose toxicity studies are available for aluminium potassium fluoride. In the inhalation repeated dose toxicity studies no systemic effects were observed. Therefore a dermal long-term DNEL cannot be quantified using the inhalation route as starting point.

For the structural analogue of aluminium potassium fluoride, cryolite,effects on postnatal growth evidenced by significantly decreased pup body weights during lactation as well as pathologic gross findings in several organs of the pups resulted from dose levels without any significant parental toxicity in the two-generation study (oral route) (Pharmaco LSR, Inc., 1994). Because these effects occurred without any significant sign for parental toxicity it is considered to be indicative for a specific toxic potential of cryolite adverse to postnatal development. The respective NOAEL for these effects in this study was 42 mg cryolite/kg bw/day. This level will be used for derivation of the dermal DNEL of aluminium potassium fluoride

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 42 mg/kg bw/day

Read-across using the two-generation study of the structural analogue cryolite: developmental toxic effects were observed at the dose level of 128 mg/kg bw/day and higher.

Step 2) Modification of starting point

100 / 0.6

 

 

Conversion into dermal NAEL (in mg/kg bw/day) assuming 100% oral absorption and 0.6% dermal absorption.

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Default assessment factor for allometric scaling and remaining uncertainties as taken from the REACH guidance.

Intraspecies

10

Default assessment factor taken from REACH.

Exposure duration

1

Not applicable

Dose response

1

 

Quality of database

1

 

Uncertainty factor (read-across)

1

Toxicokinetics

No additional factor is needed as in Step 2) substance-specific absorption figures are used.

 

Toxicodynamics

The main difference between cryolite and aluminium potassium fluoride in terms of constituting elements is the alkali metal cation, namely sodiumvs.potassium. Both these elements are essential constituents and two of the most abundant ions in all humans, as well as in all animal species. As systemic toxicity of both cryolite and aluminium potassium fluoride is primarily governed by accumulation of the fluoride formed upon hydrolysis of fluoroaluminate moieties, the same type of effects can be expected for the compounds. Based on the above, no differences in toxicodynamics are expected and therefore no additional factor is needed.

Step 4) Calculate DNEL

(42 x 100 / 0.6) / 4 x 2.5 x 5 x 1 x 1 x 1 x 1 = 70 mg/kg bw/day

 

No data are available concerning local effects after repeated dermal contact with aluminium potassium fluoride. The acute skin tests did not show local irritating or sensitising properties. From epidemiological data no observations on skin reactions from workers have been reported. In summary local effects by prolonged skin contact are not expected.