Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
23.5 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):
75
Modified dose descriptor starting point:
NOAEC
DNEL value:
1 763 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step, followed by a correction for the difference between respiratory rates of workers under standard conditions and under light activity in the second step. NAECcorr_inh = oral NOAEL (1000) x 1/0.38 m3/kg bw x 6.7 m3/10 m3 = 1763 mg/m3. Oral absorption is very low in rats and can per default be assumed at about 0.5 % (D’Souza and Francis, 1987). Absorption of bismuth trinitrate in humans is considered to be low and approximately the same as oral absorption in rats therefore a correction factor for differences in the rates of absorption for the oral and the inhalation routes in rats and humans is not required (see Chapter 7.1 Toxicokinetics for explanation). Therefore, NAECcorr_inh = 1763 mg/m3 x 1 = 1763 mg/m3.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC (Chapter R.8: Characterisation of dose [concentration]-response for human health)
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor of 5 for workers
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database (Chapter R.8: Characterisation of dose [concentration]-response for human health)
AF for remaining uncertainties:
1
Justification:
It is considered that there is sufficient safety factors built into the extrapolations utilised to justify omission of this “uncertain” assessment factor.
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:
no hazard identified
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:
medium hazard (no threshold derived)

Additional information - workers

There is one repeated dose oral toxicity study available, which characterised the potential toxic effects of read-across substance, bismuth metal, following oral administration for 28 days. A NOAEL of 1000 mg/kg bw/day was established for bismuth metal based on the lack of toxicologically relevant effects at the highest dose tested and was selected as starting point for DNEL derivation. No dermal DNELs were derived as dermal absorption of bismuth is expected to be negligible and bismuth trinitrate was shown to be not irritating to the skin in an in vivo test in rabbits. Local and acute inhalation DNELs were not derived because an acute inhalation study with read-across substance, dibismuth trioxide, in rats did not indicate any significant systemic or local effects up to the threshold of 5 mg/l air. The substance is considered a medium hazard for the eyes as it is classified as causing serious eye damage (category 1).

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 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:
869.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
Modification of the dose descriptors is necessary, because the routes of exposure are different between animals (oral) and humans (inhalation). For this purpose the default respiratory volume for the rat corresponding to the daily duration of human exposure is considered in the first step. NAECcorr_inh = oral NOAEL (1000) x 1/1.15 m3/kg bw = 869.6 mg/m3. Oral absorption is very low in rats and can per default be assumed at about 0.5 % (D’Souza and Francis, 1987). Absorption of bismuth trinitrate in humans is considered to be low and approximately the same as oral absorption in rats therefore a correction factor for differences in the rates of absorption for the oral and the inhalation routes in rats and humans is not required (see Chapter 7.1 Toxicokinetics for explanation). Therefore, NAECcorr_inh = 869.6 mg/m3 x 1 = 869.6 mg/m3.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC (Chapter R.8: Characterisation of dose [concentration]-response for human health)
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
No allometric scaling required for inhalation route.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
10
Justification:
Default assessment factor of 10 for general population
AF for the quality of the whole database:
1
Justification:
Default assessment factor for good/standard quality of database (Chapter R.8: Characterisation of dose [concentration]-response for human health)
AF for remaining uncertainties:
1
Justification:
It is considered that there is sufficient safety factors built into the extrapolations utilised to justify omission of this “uncertain” assessment factor.
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:
no hazard identified
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:
1.7 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):
600
Modified dose descriptor starting point:
NOAEL
DNEL value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No route to route extrapolation required. Assuming that oral absorption in rats = oral absorption in humans.
AF for dose response relationship:
1
Justification:
Default assessment factor when the starting point for the DNEL calculation is a NOAEC
AF for differences in duration of exposure:
6
Justification:
Default assessment factor for extrapolation from subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Factor for allometric scaling for rat
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:
1
Justification:
Default assessment factor for good/standard quality of database (Chapter R.8: Characterisation of dose [concentration]-response for human health)
AF for remaining uncertainties:
1
Justification:
It is considered that there is sufficient safety factors built into the extrapolations utilised to justify omission of this “uncertain” assessment factor
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

There is one repeated dose oral toxicity study available, which characterised the potential toxic effects of read-across substance, bismuth metal, following oral administration for 28 days. A NOAEL of 1000 mg/kg bw/day was established for bismuth metal based on the lack of toxicologically relevant effects at the highest dose tested and was selected as starting point for DNEL derivation for long-term systemic effects via inhalation and long-term oral systemic effects. No acute oral systemic DNEL was derived because an acute oral toxicity study with read-across substance, bismuth subsalicylate, in rats did not indicate any systemic effects up to the threshold of 2000 mg/kg bw/day. No dermal DNELs were derived as dermal absorption of bismuth is expected to be negligible and bismuth subnitrate was shown to be not irritating to the skin in an in vivo test in rabbits. Local and acute inhalation DNELs were not derived because an acute inhalation study with read-across substance, dibismuth trioxide, in rats did not indicate any significant systemic or local effects up to the threshold of 5 mg/l air; in addition, the general population is not expected to be at risk by this route of exposure. The substance is considered a medium hazard for the eyes as it is classified as causing serious eye damage (category 1).