Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.75 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):
140
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:
no justification for route to route extrapolation required
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1.4
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Modified dose descriptor starting point:
LOAEC

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:
95 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
9 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
1% dermal absorption applied to NOAEL
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
95 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):
100
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
9 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
1% dermal absorption applied to NOAEL
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
Worker
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
correlation with long-term exposure. No dermal toxicity observed.

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

Sodium bromide is not irritating to skin and eyes, not sensitizing to skin and has a dermal LD50>2000 mg/kg bw with no systemic or local toxicity observed. It is considered unlikely that exposure of workers via the dermal route will be unsafe. Nevertheless, in order to avoid any potential exposure, workers are instructed to wear protective gloves, body covering clothes and boots.

Exposure by the inhalation route is unlikely due to the particle size.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.66 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):
200
Modified dose descriptor starting point:
NOAEC
Value:
332 mg/m³
Explanation for the modification of the dose descriptor starting point:
no justification for route to route extrapolation required
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
general public
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
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:
95 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
9 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
1% dermal absorption applied to NOAEL
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
no difference between workers and the general population with regard to dermal absorption.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
95 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):
100
DNEL extrapolated from long term DNEL
Modified dose descriptor starting point:
NOAEL
Value:
9 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
1% dermal absorption applied to NOAEL
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
no difference between workers and the general population with regard to dermal absorption.
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
correlation with long-term exposure. No dermal toxicity observed.

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:
0.475 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
95 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General public
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
42 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
Justification:
General population
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

DNEL for general population was calculated for oral, dermal and inhalation routes of exposure based on experimental data with sodium bromide and by read-across to the analogous substances ammonium and potassium bromide (NOAEL of 95 mg/kg bw in a 90-day repeat dose oral study). The ion of concern is the bromide ion.

In consideration of the human volunteer data giving an NOAEL value for bromide effects in humans and the typical average daily bromide intake from food, Member State BPD Competent Authorities agreed that limiting derivation of hazard endpoints from animal studies was incorrect. Hazard endpoint setting should consider all relevant available data and be consistent with the level at which it has been shown in the appropriate model, in this case humans, that there are no observed adverse effects.

Therefore, the oral long-term systemic DNEL value is set in line with the Acceptable Daily Intake (ADI) value of 0.4 mg bromide/kg bw/day set by the European Medicines Agency based on the NOAEL derived from human studies and the measured human intake of bromide from background sources such as food and water. In view of the low dermal absorption of bromide ions, the dermal DNELs should not be greater than the oral DNEL.

Sodium bromide was determined experimentally as a non-sensitizer for skin and was not irritant in either skin or eye tests.