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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.93 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
12.5
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
61.67 mg/m³
Explanation for the modification of the dose descriptor starting point:

Figure R.8-3 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on results from a two-generation study in which administration of test material to male/female rats took place for > 181 days (26 weeks) and detailed investigation of reproductive organs was conducted during performance of the sub-chronic study. No assessment factor to account for difference in duration is therefore considered necessary (see Guidance on Assessment Factors to Derive a DNEL, ECETOC Technical Report No. 110; October 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required because differences in breathing between rat and human already accounted for during modification of starting point.
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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:
70 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
3 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Example B.5 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on results from a two-generation study in which administration of test material to male/female rats took place for > 181 days (26 weeks) and detailed investigation of reproductive organs was conducted during performance of the sub-chronic study. No assessment factor to account for difference in duration is therefore considered necessary (see Guidance on Assessment Factors to Derive a DNEL, ECETOC Technical Report No. 110; October 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human).
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
5
Justification:
Default assessment factor for workers.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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

The substance is not acutely toxic via the oral or dermal routes (LD50 > 2000 mg/kg), has a low vapour pressure at ambient temperature, exposure by the inhalation route is unlikely due to particle size, and no evidence of skin corrosion/irritation or skin sensitisation has been reported. It is therefore considered that risk management measures applied in the industrial and professional setting to guard against effects of the substance on fertility will prevent substantial exposure of humans. Nevertheless, long-term systemic DNELs have been derived for the respiratory and dermal routes as a precaution.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.87 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
21.74 mg/m³
Explanation for the modification of the dose descriptor starting point:

Figure R.8-3 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on results from a two-generation study in which administration of test material to male/female rats took place for > 181 days (26 weeks) and detailed investigation of reproductive organs was conducted during performance of the sub-chronic study. No assessment factor to account for difference in duration is therefore considered necessary (see Guidance on Assessment Factors to Derive a DNEL, ECETOC Technical Report No. 110; October 2010).
AF for interspecies differences (allometric scaling):
1
Justification:
Allometric scaling not required because differences in breathing between rat and human already accounted for during modification of starting point
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
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:
25 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
2 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Example B.5 of ECHA Guidance on information requirements and chemical safety assessment Chapter R.8: Characterisation of dose [concentration]-response for human health (Version 2.1; November 2012).

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on results from a two-generation study in which administration of test material to male/female rats took place for > 181 days (26 weeks) and detailed investigation of reproductive organs was conducted during performance of the sub-chronic study. No assessment factor to account for difference in duration is therefore considered necessary (see Guidance on Assessment Factors to Derive a DNEL, ECETOC Technical Report No. 110; October 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human).
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
5
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
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:
0.5 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
50 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation not required.

AF for dose response relationship:
1
Justification:
Default assessment factor applied because starting point for DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
1
Justification:
The DNEL is based on results from a two-generation study in which administration of test material to male/female rats took place for > 181 days (26 weeks) and detailed investigation of reproductive organs was conducted during performance of the sub-chronic study. No assessment factor to account for difference in duration is therefore considered necessary (see Guidance on Assessment Factors to Derive a DNEL, ECETOC Technical Report No. 110; October 2010).
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling to correct for differences in metabolic rate (rat to human).
AF for other interspecies differences:
2.5
Justification:
Default correction for other interspecies differences to allow for variation in toxicokinetics and toxicodynamics.
AF for intraspecies differences:
10
Justification:
Default assessment factor for general population.
AF for the quality of the whole database:
1
Justification:
The starting point NOAEL was obtained from a GLP guideline study.
AF for remaining uncertainties:
1
Justification:
No other assessment factor is considered necessary.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Explanation for the modification of the dose descriptor starting point:

Investigation of acute toxicity of the substance via the oral route reported no mortalities, signs of systemic toxicity or abnormalities at necropsy that would lead to classification. It can therefore be concluded that the substance causes no systemic effects under acute exposure conditions and that derivation of a DNEL is unnecessary because the long-term oral DNEL is protective for consumers with respect to effects on fertility.

Justification:
General population

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

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 (NOAEL of 50 mg/kg bw in a two generation reproduction 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.