Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.54 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
DNEL value:
226 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
114 mg/m³
AF for dose response relationship:
1
Justification:
A factor of 1 is applied as the starting point for DNEL derivation is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
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.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Four repeated dose toxicity studies are available. Additionally, genotoxicity, immunotoxicity (sensitisation) and reprotoxicity are available, none of which is identifying a major reason for concern.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20.5 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
DNEL value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Conversion into dermal NOAEL assuming 100% oral absorption and 0.65% dermal absorption for potassium tetrafluoroborate.
AF for dose response relationship:
1
Justification:
A factor of 1 is applied as the starting point for DNEL derivation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling in case of a study with rats
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers
AF for the quality of the whole database:
1
Justification:
Four repeated dose toxicity studies are available. Additionally, genotoxicity, immunotoxicity (sensitisation) and reprotoxicity are available, none of which is identifying a major reason for concern.
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:
no hazard identified

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 not classified for acute dermal, inhalation, and oral toxicity. The substance is also not classified as irritating to the skin and not sensitizing.

 

Long-term toxicity

The toxicity upon repeated oral exposure was examined in four studies; two oral toxicity studies and two inhalation toxicity studies. Based on the adverse effects observed in these studies, the no observed adverse effect level (NOAEL) for KBF4 was 40 mg/kg body weight for oral exposure and 226 mg/m3 for inhalation exposure. Since only a sub-acute oral and subchronic inhalation toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for the dermal route. As described in the toxicokinetic statement, 0.65 and 1.8% dermal absorption is assumed for workers and the general population, respectively.

 

Reproductive and developmental toxicity effects

The reproductive and developmental toxicity NOAELs are at the same or higher level as for repeated dose toxicity. Therefore the DNEL derived for repeated dose toxicity will also cover the reproductive and developmental toxic effects. No specific DNELs will be derived for these endpoints

 

Worker DNELs

Long-term

 

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

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 226 mg/m3

high level tested, effects in body weights and food consumption.

Step 2) Modification of starting point

0.75

 

 

0.67

 

Correction for exposure time of exposure (6 hour to 8 hour exposure)

 

Correction for activity driven differences of respiratory volumes in workers compared to rats in rest.

Modified dose-desciptor

74 * 0.75 * 0.67 = 114 mg/ 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

5

Default assessment factor for workers

Exposure duration

2

Extrapolation to chronic exposure based on a subchronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

114 / (2.5 x 5 x 2 x 1 x 1) =4.6 mg/m3

 

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

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 40 mg/kg bw/day

Based on effects on mortality, body weight and food consumption.

Step 2) Modification of starting point

100/0.65

Conversion into dermal NOAEL (in mg/kg bw/day) assuming 100% oral absorption and 0.65% dermal absorption for pure potassium tetrafluoroborate

Modified dose-desciptor

40*(100/0.650) = 6154 mg/kg bw

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Assessment factor for allometric scaling.

Intraspecies

5

Default assessment factor 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

 

6154 / (4 x 2.5 x 5 x 6 x 1 x 1) =20.5 mg/kg bw/day

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.13 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEC
DNEL value:
226 mg/m³
Modified dose descriptor starting point:
NOAEC
DNEL value:
56.5 mg/m³
AF for dose response relationship:
1
Justification:
A factor of 1 is applied as the starting point for DNEL derivation is a NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from subchronic to chronic exposure
AF for interspecies differences (allometric scaling):
1
Justification:
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.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Four repeated dose toxicity studies are available. Additionally, genotoxicity, immunotoxicity (sensitisation) and reprotoxicity are available, none of which is identifying a major reason for concern.
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:
DNEL (Derived No Effect Level)
Value:
3.7 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
DNEL value:
40 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Conversion into dermal NOAEL assuming 100% oral absorption and 1.8% dermal absorption for potassium tetrafluoroborate.
AF for dose response relationship:
1
Justification:
A factor of 1 is applied as the starting point for DNEL derivation is a NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation from sub-acute to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Assessment factor for allometric scaling in case of a study with rats
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Four repeated dose toxicity studies are available. Additionally, genotoxicity, immunotoxicity (sensitisation) and reprotoxicity are available, none of which is identifying a major reason for concern.
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:
67 µg/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
DNEL value:
40 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:
A factor of 1 is applied as the starting point for DNEL derivation is a clear NOAEL
AF for differences in duration of exposure:
6
Justification:
Extrapolation for sub-acute to chronic study
AF for interspecies differences (allometric scaling):
2.5
Justification:
Default assessment factor
AF for other interspecies differences:
4
Justification:
Assessment factor for allometric scaling in case of a study with rats
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population
AF for the quality of the whole database:
1
Justification:
Four repeated dose toxicity studies are available. Additionally, genotoxicity, immunotoxicity (sensitisation) and reprotoxicity are available, none of which is identifying a major reason for concern.
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

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 not classified for acute dermal, inhalation, and oral toxicity. The substance is also not classified as irritating to the skin and not sensitizing.

 

Long-term toxicity

The toxicity upon repeated oral exposure was examined in four studies; two oral toxicity studies and two inhalation toxicity studies. Based on the adverse effects observed in these studies, the no observed adverse effect level (NOAEL) for KBF4 was 40 mg/kg body weight for oral exposure and 226 mg/m3 for inhalation exposure. Since only a sub-acute oral and subchronic inhalation toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for the dermal route. As described in the toxicokinetic statement, 0.65 and 1.8% dermal absorption is assumed for workers and the general population, respectively.

 

Reproductive and developmental toxicity effects

The reproductive and developmental toxicity NOAELs are at the same or higher level as for repeated dose toxicity. Therefore the DNEL derived for repeated dose toxicity will also cover the reproductive and developmental toxic effects. No specific DNELs will be derived for these endpoints

General population DNELs

Long-term

 

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

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEC: 226 mg/m3

Based on impaired growth and reduced food intake.

Step 2) Modification of starting point

0.25

Correction for exposure time of exposure (6 hour to 24 hour exposure)

Modified dose-desciptor

226 * 0.25 = 56.5 mg/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

10

Default assessment factor

Exposure duration

2

Extrapolation to chronic exposure based on a subchronic toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

56.5 / (2.5 x 10 x 2 x 1 x 1) =1.13 mg/m3

 

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

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 40 mg/kg bw/day

Based on effects on mortality, body weight and food consumption.

Step 2) Modification of starting point

-

 

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Assessment factor for allometric scaling.

Intraspecies

10

Default assessment factor

Exposure duration

6

Extrapolation to chronic exposure based on a sub-acute toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

40 / (4 x 2.5 x 10 x 6 x 1 x 1) =67 µg/kg bw/day

 

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

Description

Value

Remark

Step 1) Relevant dose-descriptor

NOAEL: 40 mg/kg bw/day

Based on effects on mortality, body weight and food consumption.

Step 2) Modification of starting point

-

Conversion into dermal NOAEL (in mg/kg bw/day) assuming 100% oral absorption and 1.8% dermal absorption for pure potassium tetrafluoroborate

Modified dose-desciptor

40*(100/1.8) = 2222 mg/kg bw

Step 3) Assessment factors

 

 

Interspecies

4 x 2.5

Assessment factor for allometric scaling.

Intraspecies

10

Default assessment factor

Exposure duration

6

Extrapolation to chronic exposure based on a sub-acute toxicity study

Dose response

1

 

Quality of database

1

 

DNEL

Value

 

2222 / (4 x 2.5 x 10 x 6 x 1 x 1) =3.7 mg/kg bw/day