Registration Dossier

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

173 µg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

150

Modified dose descriptor starting point:

NOAEC

Value:

25.9 mg/m³

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 NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from sub-acute 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:

2

Justification:

An assessment factor of 2 is applied since the DNEL has been derived from the structural analogue potassium tetrafluoroborate

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

46 µg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Value:

27.9 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal study available. Conversion into dermal NOAEL assuming no difference in absorption between the oral and dermal route of exposure.

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:

2

Justification:

An assessment factor of 2 is applied since the DNEL has been derived from the structural analogue potassium tetrafluoroborate

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

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. However, due to corrosive properties of tetrafluoroboric acid, no data is available on the acute toxicity and sensitization of tetrafluoroboric acidand therefore no DNEL could be derived.

Long-term toxicity

No repeated dose studies on tetrafluoroboric acid were available. Furthermore, since the test substance is corrosive, testing of tetrafluoroboric acid will result in unnecessary suffering for the animal. Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. Therefore, information from the structural analogue potassium tetrafluoroborate was used to determine the possible effects of tetrafluoroboric acid after repeated exposure. The toxicity upon repeated exposure was examined in three studies in rats; two subacute oral toxicity studies and one subacute inhalation toxicity study. Based on the adverse effects observed in these studies, the no observed adverse effect level (NOAEL) for potassium tetrafluoroborate was 40 mg/kg body weight for oral exposure (i.e. the lowest dose tested in the reproduction/developmental toxicity screening study; the NOAEL in the other oral study was 320 mg/kg body weight) and 72 mg/m³for inhalation exposure.

Reproductive and developmental toxicity effects

Also no reproduction toxicity studies on tetrafluoroboric acid were available. The reproductive and developmental toxicity NOAELs obtained in the oral reproduction/developmental toxicity screening study with potassium tetrafluoroborate are at the same or higher level as the above NOAEL for repeated dose oral toxicity. Therefore, the DNEL derived for repeated dose oral toxicity will also cover reproductive and developmental toxic effects. No specific DNELs will be derived for the latter endpoints

DNEL derivation

For short-term toxicity and local effects, no DNEL could be derived since no data is available due to the corrosive properties of tetrafluoroboric acid. For long-term toxicity, DNELs have been derived from the structural analogue potassium tetrafluoroborate. Regarding systemic effects, a NOAEL of 40 mg/kg body weight for oral exposure and 72 mg/m3 for inhalation exposure have been used to derive the DNELs. The default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation, 50% for oral and 50% for dermal absorption. Since only a sub-acute oral and inhalation toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for the dermal route.

Since HBF4 is a corrosive substance, exposure of the skin to HBF4 will be quickly noticed by workers, leading to washing / rinsing of the skin and long-term dermal exposure is not very likely to occur. Therefore, the derived DNEL for systemic effects only applies to preparations in which HBF4 is present in concentrations below the corrosivity threshold, where the direct corrosive effects will not be directly noticed by workers.

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: 74 mg/m3	Based on impaired growth and reduced food intake.
Step 2) Modification of starting point	KBF₄: 125.91 g/mol HBF₄: 87.81 g/mol 0.75 0.67	Correction for molecular weight Correction for duration of exposure (6 hour to 8 hour exposure) Correction for activity driven differences of respiratory volumes in workers compared to workers in rest.
Modified dose-descriptor	74 * (87.81 / 125.91) * 0.75 * 0.67 = 25.9 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	6	Extrapolation to chronic exposure based on a sub-acute toxicity study
Dose response	1
Quality of database	2	Read-across
DNEL	Value
	25.9 / (2.5 x 5 x 6 x 1 x 2) = 25.9 / 150 = 173µg/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 reduced body weight and food consumption at the next higher dose (116.5 mg/kg bw).
Step 2) Modification of starting point	KBF₄: 125.91 g/mol HBF₄: 87.81 g/mol	Correction for molecular weight
Modified dose-descriptor	40 * (87.81 / 125.91) = 27.9 mg/kg bw
Step 3) Assessment factors
Interspecies	4 x 2.5	Default assessment factors for allometric scaling and remaining interspecies differences
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	2	Read-across
DNEL	Value
	27.9 / (4 x 2.5 x 5 x 6 x 1 x 2) = 27.9 / 600 =46 µg/kg bw/day

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

43 µg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

By inhalation

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

300

Modified dose descriptor starting point:

NOAEC

Value:

12.9 mg/m³

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 NOAEL

AF for differences in duration of exposure:

6

Justification:

Extrapolation from sub-acute 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:

2

Justification:

An assessment factor of 2 is applied since the DNEL has been derived from the structural analogue potassium tetrafluoroborate

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23 µg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1 200

Modified dose descriptor starting point:

NOAEL

Value:

27.9 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No dermal study available. Conversion into dermal NOAEL assuming no difference in absorption between the oral and dermal route of exposure.

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:

2

Justification:

An assessment factor of 2 is applied since the DNEL has been derived from the structural analogue potassium tetrafluoroborate

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

23 µg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

1 200

Modified dose descriptor starting point:

NOAEL

Value:

27.9 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:

2

Justification:

An assessment factor of 2 is applied since the DNEL has been derived from the structural analogue potassium tetrafluoroborate

Hazard assessment conclusion:

high hazard (no threshold derived)

Hazard assessment conclusion:

high hazard (no threshold derived)

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. However, due to corrosive properties of tetrafluoroboric acid, no data is available on the acute toxicity and sensitization of tetrafluoroboric acidand therefore no DNEL could be derived.

Long-term toxicity

No repeated dose studies on tetrafluoroboric acid were available. Furthermore, since the test substance is corrosive, testing of tetrafluoroboric acid will result in unnecessary suffering for the animal. Article 13 of the REACH legislation states that, in case no appropriate animal studies are available for assessment, information should be generated whenever possible by means other than vertebrate animal tests, i. e. applying alternative methods such as in vitro tests, QSARs, grouping and read-across. Therefore, information from the structural analogue potassium tetrafluoroborate was used to determine the possible effects of tetrafluoroboric acid after repeated exposure. The toxicity upon repeated exposure was examined in three studies in rats; two subacute oral toxicity studies and one subacute inhalation toxicity study. Based on the adverse effects observed in these studies, the no observed adverse effect level (NOAEL) for potassium tetrafluoroborate was 40 mg/kg body weight for oral exposure (i.e. the lowest dose tested in the reproduction/developmental toxicity screening study; the NOAEL in the other oral study was 320 mg/kg body weight) and 72 mg/m3 for inhalation exposure.

Reproductive and developmental toxicity effects

Also no reproduction toxicity studies on tetrafluoroboric acid were available. The reproductive and developmental toxicity NOAELs obtained in the oral reproduction/developmental toxicity screening study with potassium tetrafluoroborate are at the same or higher level as the above NOAEL for repeated dose oral toxicity. Therefore, the DNEL derived for repeated dose oral toxicity will also cover reproductive and developmental toxic effects. No specific DNELs will be derived for the latter endpoints

DNEL derivation

For short-term toxicity and local effects, no DNEL could be derived since no data is available due to the corrosive properties of tetrafluoroboric acid. For long-term toxicity, DNELs have been derived from the structural analogue potassium tetrafluoroborate. Regarding systemic effects, a NOAEL of40 mg/kg body weight for oral exposure and 72 mg/m3 for inhalation exposure have been used to derive the DNELs. The default absorption values from the REACH guidance (Chapter 8, R.8.4.2) are used for DNEL derivation, namely: 100% for inhalation, 50% for oral and 50% for dermal absorption. Since only a sub-acute oral and inhalation toxicity study is available a route-to-route extrapolation is needed to derive the DNELs for the dermal route.

Since HBF4 is a corrosive substance, exposure of the skin to HBF4 will be quickly noticed, leading to washing / rinsing of the skin and long-term dermal exposure is not very likely to occur. Therefore, the derived DNEL for systemic effects only applies to preparations in which HBF4 is present in concentrations below the corrosivity threshold, where the direct corrosive effects will not be directly noticed.

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: 74 mg/m3	Based on impaired growth and reduced food intake.
Step 2) Modification of starting point	KBF₄: 125.91 g/mol HBF₄: 87.81 g/mol 0.25	Correction for molecular weight Correction for duration of exposure (6 hour to 24 hour exposure)
Modified dose-descriptor	74 (87.81 / 125.91) 0.25 = 12.9 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 for general population
Exposure duration	6	Extrapolation to chronic exposure based on a sub-acute toxicity study
Dose response	1
Quality of database	2	Read-across
DNEL	Value
	12.9 / (2.5 x 10 x 6 x 1 x 2) = 12.9 / 300 =43µg/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 reduced body weight and food consumption at the next higher dose (116.5 mg/kg bw).
Step 2) Modification of starting point	KBF₄: 125.91 g/mol HBF₄: 87.81 g/mol	Correction for molecular weight
Modified dose-descriptor	40 * (87.81 / 125.91) = 27.9 mg/kg bw
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	2	Read-across
DNEL	Value
	27.9 / (4 x 2.5 x 10 x 6 x 1 x 2) = 27.9 / 1200 =23 µg/kg bw/day

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 reduced body weight and food consumption at the next higher dose (116.5 mg/kg bw).
Step 2) Modification of starting point	KBF₄: 125.91 g/mol HBF₄: 87.81 g/mol	Correction for molecular weight
Modified dose-descriptor	40 *(87.81 / 125.91)= 27.9mg/kg bw
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	2	Read-across
DNEL	Value
	27.9 / (4 x 2.5 x 10 x 6 x 1 x 2) = 27.9 / 1200 =23 µg/kg bw/day

Registration Dossier

Registration Dossier

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Diss Factsheets

Tetrafluoroboric acid

Toxicological Summary

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

Workers - Hazard for the eyes

Local effects

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

Local effects

Long term exposure

Acute/short term exposure

General Population - Hazard via oral route

Systemic effects

Long term exposure

DNEL related information

Acute/short term exposure

DNEL related information

General Population - Hazard for the eyes

Local effects

Additional information - General Population