Dibismuth carbonate dioxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

calculation (if not (Q)SAR)

Remarks:

Migrated phrase: estimated by calculation

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A written assessment of toxicokinetic behaviour is considered appropriate for the substance. The substance displays only minor toxicological effects in any of the studies proposed, and is deemed to be be not harmful for health effects. As such, it is deemed inappropriate in terms of animal welfare to conduct a toxicokinetic assessment when no harmful effects are predicted based on known toxicology. A written assessment has therefore been prepared to address this endpoint.

Materials and methods

Principles of method if other than guideline:

A written assessment based on the toxicological profile of the substance.

Test material

Test material information

Constituent 1

Reference substance name:

Dibismuth carbonate dioxide

EC Number:

227-567-9

EC Name:

Dibismuth carbonate dioxide

Cas Number:

5892-10-4

Molecular formula:

CBi2O5

IUPAC Name:

({[(oxobismuthanyl)oxy]carbonyl}oxy)bismuthanone

Test material form:

solid

Test animals

Species:

other: not applicable

Details on test animals or test system and environmental conditions:

Not applicable

Administration / exposure

Route of administration:

other: not applicable

Details on exposure:

Not applicable

Duration and frequency of treatment / exposure:

Not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
Not applicable

No. of animals per sex per dose / concentration:

Not applicable

Positive control reference chemical:

Not applicable

Details on study design:

Not applicable

Details on dosing and sampling:

Not applicable

Results and discussion

Preliminary studies:

Not applicable

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Not applicable

Details on distribution in tissues:

Not applicable

Details on excretion:

Not applicable

Metabolite characterisation studies

Details on metabolites:

Not applicable

Applicant's summary and conclusion

Conclusions:

The bismuth portion of pharmaceutical preparations of bismuth subcarbonate is poorly absorbed from the gastrointestinal tract with an oral bioavailability generally reported to be < 1%. There are very few data on dermal absorption of bismuth, however, absorption via this route is expected to be low. Based on particle size distribution data and modelling on deposition in the respiratory tract, it is estimated that between 4.6% to 8.6% of bismuth subcarbonate may be absorbed via inhalation.
The small amount of bismuth that is absorbed is distributed to various organs with the highest concentration expected to be in the kidney. Bismuth can cross the blood-brain barrier. The results of a study in guinea pigs with radiobismuth suggests poor placental transfer of bismuth (<1%). Excretion of absorbed bismuth is via the urinary and faecal routes. The distribution half-life of bismuth is 1 to 4 hours, the plasma half-life is 5 to 11 days and the urinary excretion half-life lasts between 21 to 72 days. Unabsorbed bismuth is excreted in the faeces.

Executive summary:

A toxicokinetics assessment was conducted for bismuth subcarbonate using available data including data from the published literature.

Absorption:The bismuth portion of pharmaceutical preparations of bismuth subcarbonate is poorly absorbed from the gastrointestinal tract with an oral bioavailability generally reported to be < 1%. There are very few data on the dermal absorption of bismuth, however, absorption via this route is expected to be low.  Based on particle size distribution data and modelling on deposition in the respiratory tract, it is estimated that between 4.6% to 8.6% of bismuth subcarbonate may be absorbed via inhalation.

Distribution: The small amount of bismuth that is absorbed is distributed to various organs with the highest concentration expected to be in the kidney. The results of a study in guinea pigs with radiobismuth suggests poor placental transfer of bismuth (<1%), however, bismuth can cross the blood-brain barrier. The distribution half-life of bismuth is 1 to 4 hours and the plasma half-life is 5 to 11 days.

Elimination: Excretion of absorbed bismuth is via the urinary and faecal routes and the urinary excretion half-life lasts between 21 to 72 days. Unabsorbed bismuth is excreted in the faeces.