Registration Dossier
Registration Dossier
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EC number: 203-743-0 | CAS number: 110-17-8
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- Not stated
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Peer-reviewed study with sufficient detail to enable confident assessment of the method and interpretation of the results
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 948
Materials and methods
- Objective of study:
- distribution
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Distribution of endogenous fumaric acid in several tissues of the rat was determined using column partition chromatography for analysing organic acids in biological samples.
Fumaric acid levels in brain, kidney,liver, gastrocnemius muscle and blood from 12 rats - pooled samples collected after 18 hours fasting. - GLP compliance:
- no
- Remarks:
- Study conducted prior to establishment of GLP
Test material
- Reference substance name:
- Fumaric acid
- EC Number:
- 203-743-0
- EC Name:
- Fumaric acid
- Cas Number:
- 110-17-8
- Molecular formula:
- C4H4O4
- IUPAC Name:
- but-2-enedioic acid
- Details on test material:
- Fumaric acid.
Levels of fumarate were assessed in various tissues.
Constituent 1
- Radiolabelling:
- no
Test animals
- Species:
- rat
- Strain:
- not specified
- Sex:
- not specified
- Details on test animals or test system and environmental conditions:
- Adult rats were maintained on a stock diet and fasted for 18 hours prior to sampling.
Administration / exposure
- Route of administration:
- other: Endogenous levels in rats maintained on stock diet were assessed. The rats were not treated with fumaric acid
- Vehicle:
- other: not applicable
- Details on exposure:
- Rats were fasted for 18 hrs. Endogenous levels of fumaric acid were assessed in tissues from rats maintained on stock diet.
- Duration and frequency of treatment / exposure:
- Not applicable
Doses / concentrations
- Remarks:
- Doses / Concentrations:
Not applicable
- No. of animals per sex per dose / concentration:
- 12 animals
- Control animals:
- no
- Positive control reference chemical:
- Not applicable
- Details on study design:
- Brain, kidney, liver, gastrocnemius muscle and blood was pooled from all rats to determine endogenous fumarate concentrations. The column partition method was used elute various organic acids, including fumaric acid, and the concentration of fumaric acid in each fraction was determined.
- Details on dosing and sampling:
- Not applicable
- Statistics:
- Not applicable
Results and discussion
- Preliminary studies:
- Not applicable
Main ADME results
- Type:
- distribution
- Results:
- Recovery studies demonstrate partition chromatography techniques are applicable to animal tissues. Significant fumarate concentrations found in various rat tissues, particularly brain, give analytical support to citric acid cycle metabolism.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Not applicable
- Details on distribution in tissues:
- Average concentration of fumaric acid (mg/100g wet tissue) in brain, kidney, liver, gastrocnemic muscle and blood was 15.0, 9.5, 7.8, 2.3, and <0.3, respectively.
The results give analytical support to the importance of fumaric acid in citric acid cycle metabolic processes.
- Details on excretion:
- No details
Metabolite characterisation studies
- Metabolites identified:
- not measured
- Details on metabolites:
- No details
Any other information on results incl. tables
Observed distribution of fumarate in pooled tissues of 12 rats fasted for 18 hrs
| Tissue | No. of determinations | Average fumaric acid measured (ug) |
Standard deviation | Average concentration of fumaric acid (mg/100 g wet tissue) |
| Brain | 2 | 830 | Range of measured values, 40 ug | 15.0 |
| Kidney | 4 | 404 | + 65 | 9.5 |
| Liver | 4 | 172 | + 5.7 | 7.8 |
| Gastrocnemis muscle | 4 | 127 | + 7.8 | 2.3 |
| Blood | 3 | 16 | <0.3 |
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): other: Endogenous fumaric acid is distributed to various tissues in the body, with brain representing the highest concentration
A quantitative measure of fumaric acid in the tissues of the rats support the position that fumaric acid is an important metabolic intermediate in the citric acid cycle. - Executive summary:
A quantitative measure of fumaric acid in the tissues of the rats support the position that fumaric acid is an important metabolic intermediate in the citric acid cycle.
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