Registration Dossier

Administrative data

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
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 409.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction for respiratory rate and volume (rat to human worker): (6.7m3/d/10m3/d) *(1/0.38 m3/kg) (default). Therefore the corrected NOAEC for repeated dose systemic effects via the inhalation route is: 800*(6.7/10*1/0.38) = 800*1.76 = 1409.7 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
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:
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
DNEL extrapolated from long term DNEL

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
Modified dose descriptor starting point:
NOAEL
DNEL value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

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 DNEL for dermal route 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. 800 mg/kg/bw : 300 (Overall assessment factor)= 2.7 mg/kg/bw.
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:
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
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

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

For inhalation route the DNEL calculated is 9.4 mg/m3. This value is obtained by ratio between NOAEC for repeated dose systemic effects via the inhalation route (1409.7 mg/m3)and total assessment factor of 150.

The DNEL for dermal route 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. 800 mg/kg/bw : 300 (Overall assessment factor)= 2.7 mg/kg/bw.

According to the CLP Regulation (EC n.1272/2008) HEBMP-H is classified H315 (Skin corr./irr. cat.2) and H318 (Eye damage/irr. cat.1) so low hazard and medium hazard are assigned respectively to dermal and eye short term effects.

The calculated DNELs are valid for both the acid and salt HEBMP-H substances since once absorbed the HEBMP-H 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
Modified dose descriptor starting point:
NOAEC
DNEL value:
696 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction for respiratory rate and volume (rat to human consumer): (1/1.15 m3/kg) (default). Therefore the corrected NOAEC for repeated dose systemic effects via the inhalation route is: 800*(1/1.15) = 800*0.9 = 695.65 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
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:
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
DNEL extrapolated from long term DNEL

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
Modified dose descriptor starting point:
NOAEL
DNEL value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
DNEL general population dermal route = 800 mg/kg/bw (NOAEL): 600 (Overal assessment factor) = 1.3 mg/kg/bw
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:
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:
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
DNEL extrapolated from long term DNEL

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
Modified dose descriptor starting point:
NOAEL
DNEL value:
800 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No modification
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:
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:
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
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population