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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study published as a comprehensive article published in peer-reviewed journall "Toxicology".

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1977

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Two equivalent groups of 10 and 8 rats were respectively dosed for 7 days with 2.73 g/kg/day of C14 labelled L(+) monosodium tartrate and DL-monosodiu tartrate. Animals were sacrificed at different intervals before and after completion of dosing and blood, liver, bone and kidney samples were taken and weighed and analysed. Animals were also sacrificed throughout the 8 day observation period after 7 days of dosing and immediately frozen to -70 °C and subjected to whole-body autoradiography of microtome slices. Radioaxtivity in whole blkood, plasma, kidneys, liver and bone was determined after processing of samples using a scintillation counter. Kidney extracts were analysed by paper chromatography and GC-MS ti identify the form in which tartaric acid is found. Finally tissue samples of kidney were fixed in formaline-saline and processed in paraffin wax for histological examination.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
99% radiochemically pure 14C monosodium tartrate.
Radiolabelling:
yes

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Male rats. 160 - 180 g at study initiation.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
Animals received a single daily dose of 2.73 mg/kg of 99% pure 14C radiolabelled monosodium L(+) tartrate for a period of 7 consecutive days. The substance was dissolved in water for oral administration by gavage.
Duration and frequency of treatment / exposure:
Single daily oral dose, 7 consecutive days.
Doses / concentrations
Remarks:
Doses / Concentrations:
2.73 mg/kg
No. of animals per sex per dose:
Only one dose. 10 male animals per dose (for analytical tests and histology).
Another 8 males subjected to same dosing regime for whole-body autoradiography studies.
Control animals:
not specified
Details on study design:
Two equivalent groups of 10 and 8 rats were respectively dosed for 7 days with 2.73 g/kg/day of C14 labelled L(+) monosodium tartrate and DL-monosodiu tartrate. Animals were sacrificed at different intervals before and after completion of dosing and blood, liver, bone and kidney samples were taken and weighed and analysed. Animals were also sacrificed throughout the 8 day observation period after 7 days of dosing and immediately frozen to -70 °C and subjected to whole-body autoradiography of microtome slices. Radioaxtivity in whole blkood, plasma, kidneys, liver and bone was determined after processing of samples using a scintillation counter. Kidney extracts were analysed by paper chromatography and GC-MS ti identify the form in which tartaric acid is found. Finally tissue samples of kidney were fixed in formaline-saline and processed in paraffin wax for histological examination.

Results and discussion

Main ADME resultsopen allclose all
Type:
absorption
Results:
Peak whole blood and plasma concentrations: 1 h after last dosage
Type:
metabolism
Results:
Biphasic decline in plasma conc. with halflives of 3 and 53 h fo monosodim (L+) tartrate
Type:
distribution
Results:
3 h after lasrt dosage labelled material detected in gastrointestinal tract, liver, kidney and bone tissue
Type:
distribution
Results:
24 h later only detectable radioactivity is in bone tissue, where it remains detectable for at least 192 h

Toxicokinetic / pharmacokinetic studies

Details on absorption:
See table above
Details on distribution in tissues:
Labelled tartrate rapidly is distributed into liver, kidney, bones and gastrointestinal tract. Labelled material disappears from all tissues after 24 h except for bone tissue, where tartrate seems to remain associated to calsium in bones for at least 192 h. Approximately 0.4% of the administered dose is distributed to bone.
Details on excretion:
Not studied, although publication refers to other studies which indicate that absorbed tartaric acid is mostly excreted unchanged in urine.

Metabolite characterisation studies

Metabolites identified:
no

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results
The sodium salt of L(+) tartrate, which is considered suitable for read-across to Potassium Sodium Tartrate is partially absorbed through the gut after oral administration and rapidly distributed and partially metabolised in blood, liver, the kidneys and bone. Tartaric acid is mostly excreted as such via urine, although it is though to be metabolised and completely oxidised in the kidneys and liver. L-tartrate salts of sodium and potassium can thereby be considered to be rapidly adsorbed, distributed, elliminated and excreted from the body, with no ability to accumulate other than for a brief period of time (up to 8 days) in bone tissue presumably as calcium tartrate.
Executive summary:

The sodium salt of L(+) tartrate, which is considered suitable for read-across to Potassium Sodium Tartrate is partially absorbed through the gut after oral administration and rapidly distributed and partially metabolised in blood, liver, the kidneys and bone. Tartaric acid is mostly excreted as such via urine, although it is though to be metabolised and completely oxidosed in the kidneys and liver. L-tartrate salts of sodium and potassium can thereby be considered to be rapidly adsorbed, distributed, elliminated and excreted from the body, with no ability to accumulate other than for a brief period of time (up to 8 days) in bone tissue presumably as calcium tartrate.