Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
70.5 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):
25
Modified dose descriptor starting point:
NOAEC
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. However, because oral absorption is very low in rats and can per default be assumed at about 0.5 %, and absorption in human following the inhalation route is calculated to be in a similar range (0.5 and 0.6 %, respectively) for bismuth metal and dibismuth trioxide (see EBRC report 2010, Derivation of oral, dermal and inhalation absorption factors for bismuth metal and bismuth compounds; IUCLID section 7.1), no further correction is considered.
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:
2
Justification:
AF for subchronic (90 day study) to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No factor for allometric scaling applied according to ECHA guidance R.8 Table R.8-4.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor
AF for intraspecies differences:
5
Justification:
Default assessment factor 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:
no hazard identified

Additional information - workers

There is a 90 day repeated dose oral toxicity study (OECD 408) available, which characterised the potential toxic effects of read-across substance, bismuth subnitrate. A NOAEL of 1000 mg/kg bw/day was established for bismuth subnitrate in this study based on the lack of toxicologically relevant effects at the highest dose tested. There is also a prenatal developmental toxicity study (OECD 414) available for the read-across substance, bismuth subnitrate. In this study, the NOEL for maternal toxicity was considered to be 1000 mg/kg bw/day. No treatment-related changes were detected in the offspring parameters measured therefore the NOEL for developmental toxicity was also considered to be 1000 mg/kg bw/day. The NOAEL from the 90 day study is selected as the starting point for DNEL derivation for long-term systemic effects via inhalation because this is the study with the longest duration.

No dermal DNELs were derived as dermal absorption of bismuth is expected to be negligible and dibismuth trioxide was shown to be not irritating to the skin in an in vitro test. Local and acute inhalation DNELs were not derived because an acute inhalation study with dibismuth trioxide in rats did not indicate any significant systemic or local effects up to the threshold of 5 mg/L air.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17.4 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):
50
Modified dose descriptor starting point:
NOAEC
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. However, because oral absorption is very low in rats and can per default be assumed at about 0.5 %, and absorption in human following the inhalation route is calculated to be in a similar range (0.5 and 0.6 %, respectively) for bismuth metal and dibismuth trioxide (see EBRC report 2010, Derivation of oral, dermal and inhalation absorption factors for bismuth metal and bismuth compounds; IUCLID section 7.1), no further correction is considered.
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:
2
Justification:
AF for subchronic (90 day study) to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
No factor for allometric scaling applied according to ECHA guidance R.8 Table R.8-4.
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

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:
5 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:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not required
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:
2
Justification:
AF for subchronic (90 day study) to chronic.
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling factor for the 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:
no hazard identified

Additional information - General Population

There is a 90 day repeated dose oral toxicity study (OECD 408) available, which characterised the potential toxic effects of read-across substance, bismuth subnitrate. A NOAEL of 1000 mg/kg bw/day was established for bismuth subnitrate in this study based on the lack of toxicologically relevant effects at the highest dose tested. There is also a prenatal developmental toxicity study (OECD 414) available for the read-across substance, bismuth subnitrate. In this study, the NOEL for maternal toxicity was considered to be 1000 mg/kg bw/day. No treatment-related changes were detected in the offspring parameters measured therefore the NOEL for developmental toxicity was also considered to be 1000 mg/kg bw/day. The NOAEL from the 90 day study is selected as the starting point for DNEL derivation for long-term systemic effects via inhalation and long-term oral systemic effects because this is the study with the longest duration.

No acute oral systemic DNEL was derived because an acute oral toxicity study with read-across substance, bismuth, 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 dibismuth trioxide was shown to be not irritating to the skin in an in vitro test. Local and acute inhalation DNELs were not derived because an acute inhalation study with 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.