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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
9.4 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):
150
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 410 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is an ongoing 90-day repeated dose toxicity study with HEBMP-xNa, conducted according to OECD Test Guideline 408 and in compliance with GLP, which study results are not yet available for derivation of DNELs. Therefore, as an interim approach, the corrected for active acid NOAEL of 800 mg/kg bw/day from the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test for HEBMP-xNa, conducted according to OECD Test Guideline 422 and in compliance with GLP, has been used. The following correction was made to the NOAEL (oral): Correction respiratory volume rat (8 hour) 1/0.38 m³/kg bw/day, Correction for respiratory volume (worker): 6.7 m³/10 m³. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 800*(1/0.38) *(6.7 m³/10 m³) = 1410 mg/m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhaled human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
oral to inhalation; absorption higher
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:
2.7 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):
300
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is an ongoing 90-day repeated dose toxicity study with HEBMP-xNa, conducted according to OECD Test Guideline 408 and in compliance with GLP, which study results are not yet available for derivation of DNELs. Therefore, as an interim approach, the corrected for active acid NOAEL of 800 mg/kg bw/day from the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test for HEBMP-xNa, conducted according to OECD Test Guideline 422 and in compliance with GLP, has been used. No correction to the dose descriptor starting point has been applied.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default (worker)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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

There is an ongoing 90-day repeated dose toxicity study with HEBMP-xNa, conducted according to OECD Test Guideline 408 and in compliance with GLP, which study results are not yet available for derivation of DNELs. Therefore, as an interim approach, the corrected for active acid NOAEL of 800 mg/ kg bw/day from the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test for HEBMP-xNa, conducted according to OECD Test Guideline 422 and in compliance with GLP, has been used.

An oral DNEL for workers (relevant to ingestion following inhalation of dusts and aerosols) has been calculated.

The DNEL is 2.7 mg active acid/kg bw/day based on the NOAEL from a subacute study. The starting NOAEL is 800 mg active acid/kg bw/day with an assessment factor of 6 applied for duration (subacute to chronic); 2.5 for interspecies differences, and an assessment factor of 5 applied for intraspecies differences and an assessment factor of 4 applied for allometric scaling.

The calculated DNELs are valid for both the acid and salt HEBMP substances since once absorbed the HEBMP salts will dissociate to become the acid and counter-ion, while the counter-ion is not expected to exhibit or influence toxicity.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.3 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):
300
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
696 mg/m³
Explanation for the modification of the dose descriptor starting point:

There is an ongoing 90-day repeated dose toxicity study with HEBMP-xNa, conducted according to OECD Test Guideline 408 and in compliance with GLP, which study results are not yet available for derivation of DNELs. Therefore, as an interim approach, the corrected for active acid NOAEL of 800 mg/kg bw/day from the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test for HEBMP-xNa, conducted according to OECD Test Guideline 422 and in compliance with GLP, has been used. The following correction was made to the NOAEL (oral): Correction respiratory volume rat (24 hour) 1/1.15 m³/kg bw. Therefore the corrected NOAEC for repeated-dose systemic effects via the inhalation route is: 800*(1/1.15) = 696 mg/m³.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
Default (oral rat to inhaled human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (consumer)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
2
Justification:
Oral to inhalation; absorption higher
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:
1.3 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
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is an ongoing 90-day repeated dose toxicity study with HEBMP-xNa, conducted according to OECD Test Guideline 408 and in compliance with GLP, which study results are not yet available for derivation of DNELs. Therefore, as an interim approach, the corrected for active acid NOAEL of 800 mg/kg bw/day from the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test for HEBMP-xNa, conducted according to OECD Test Guideline 422 and in compliance with GLP, has been used. No correction to the dose descriptor starting point has been applied.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to dermal human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (consumer)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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:
1.3 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
Dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

There is an ongoing 90-day repeated dose toxicity study with HEBMP-xNa, conducted according to OECD Test Guideline 408 and in compliance with GLP, which study results are not yet available for derivation of DNELs. Therefore, as an interim approach, the corrected for active acid NOAEL of 800 mg/kg bw/day from the combined repeated dose toxicity study with the reproduction / developmental toxicity screening test for HEBMP-xNa, conducted according to OECD Test Guideline 422 and in compliance with GLP, has been used. No correction to the dose descriptor starting point has been applied.

AF for dose response relationship:
1
Justification:
Default
AF for differences in duration of exposure:
6
Justification:
Default (subacute to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
Default (oral rat to oral human)
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default (consumer)
AF for the quality of the whole database:
1
Justification:
Default
AF for remaining uncertainties:
1
Justification:
Default
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