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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

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.

Data source

Materials and methods

Principles of method if other than guideline:
A written assessment based on the toxicological profile of the substance.

Test material

Constituent 1
Chemical structure
Reference substance name:
Bismuth citrate
EC Number:
212-390-1
EC Name:
Bismuth citrate
Cas Number:
813-93-4
Molecular formula:
C6H5O7.Bi
IUPAC Name:
bismuth(3+) 2-hydroxypropane-1,2,3-tricarboxylate
Details on test material:
Name: Bismuth citrate

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:
Interpretation of results (migrated information): other: low bioaccumulation potential based on review of study results
The bismuth portion of pharmaceutical preparations of bismuth citrate 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. Citrate is rapidly absorbed from the gastrointestinal tract with 96% to 98% absorbed within 3 hours. Based on particle size distribution data and modelling on deposition in the respiratory tract, it is estimated that between 5.0% and 9.4% of bismuth citrate 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. Citrate is a byproduct of normal oxidative pathways in the body and is normally excreted in the urine.
Executive summary:

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

Absorption:The bismuth portion of pharmaceutical preparations of bismuth citrate 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. Citrate is rapidly absorbed from the gastrointestinal tract with 96% to 98% absorbed within 3 hours.Based on particle size distribution data and modelling of deposition in the respiratory tract, it is estimated that between 5.0% and 9.4% of bismuth citrate 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. Citrate is a byproduct of normal oxidative pathways in the body and is normally excreted in the urine.