Potassium hydrogen tartrate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented report equivalent or similar to OECD guidelines

Data source

Reference

Reference Type:

publication

Title:

Renal and bone uptake of tartaric acid in rats: comparison of L(+) and DL-forms

Author:

Down WH, Sacharin RM, Chasseaud LF, Kirkpatrick D & Franklin ER

Year:

1977

Bibliographic source:

Toxicology. 8: 333-346

Materials and methods

Objective of study:

distribution

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 417 (Toxicokinetics)

Principles of method if other than guideline:

The toxicokinetics of monosodium L(+)-tartrate was studied on CFY rats in this study, and DL-tartrate was also studied as a comparison.
1. DL-[1,4-14C] tartaric acid was obtained and then was resolved into L(+)-[14C] isomer.
2. Either form of monosodium [14C] tartrate was dissolved in water and administered to animals for 7days by oral intubation.
3. One animal in each group was sacrificed immediately before the seventh day's dose, and the remainders in each group were sacrificed at intervals during the following 12 days
4. The radioactivity of samples of blood, bone and kidney and the whole-body autoradiography was measured.
5. Samples of kidney were fixed and stained with haematoxylin and eosin for histological examination.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium hydrogen tartrate

EC Number:

208-400-9

EC Name:

Sodium hydrogen tartrate

Cas Number:

526-94-3

Molecular formula:

C4H6O6.Na

IUPAC Name:

sodium hydrogen tartrate

Details on test material:

- Name of test material (as cited in study report): Monosodium L(+)-tartrate
- Molecular formula (if other than submission substance): C4H5NaO6
- Molecular weight (if other than submission substance): 172.07
- Radiochemical purity (if radiolabelling): 99%
- Locations of the label (if radiolabelling): 1,4

Radiolabelling:

yes

Remarks:

14C labeled

Test animals

Species:

rat

Strain:

other: CFY ratsm, a strain of SD origin

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Anglia Laboratory Animals, Huntingdon, Great Britain
- Weight at study initiation: 160-180 g in the first experiment, 180-200g in the further experiment.
- Individual metabolism cages: No
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

not specified

Duration and frequency of treatment / exposure:

once per day for 7 days

Doses / concentrations

Remarks:

Doses / Concentrations:
2.73 g/kg/day in the first experiment, 2.57 g/kg/day in the further experiment. All the values here are the actual ingested

No. of animals per sex per dose / concentration:

in the first experiment, 10 M in each dose group.
in the further experiment, 8 M in each dose group, and 1 rat receiving DL-tartrate died on the fifth day of dosing

Control animals:

no

Details on study design:

- Dose selection rationale: the dose level corresponded to an intermediate dietary level used in long-term toxicity studies of monnosodium L(+)-tartaric acid.

Details on dosing and sampling:

PHARMACOKINETIC STUDY (Absorption, distribution, excretion)
- Tissues and body fluids sampled : blood, plasma, kidney, bone
- Time and frequency of sampling:one animal in each group was sacrificed immediately before the seventh day's dose, and the remainder in each group were sacrificed at intervals during the following 12 days. in the further experiment, all rats sacrificed at 6 h after the seventh day's dose.

Statistics:

not mentioned

Results and discussion

Main ADME results

Main ADME results 1

Type:

distribution

Results:

the initial decline of L(+)-tartrate plasma concentration of radioactivity was rapid

Main ADME results 2

Type:

distribution

Results:

L(+)-tartrate was not retained in the kidneys and bone after dosing

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

At 3 h after the last dose of L(+)-tartrate, the radioactivity was mainly present in the gastrointestinal tract, liver, kidneys and bone. Radioactivity in the kidney was mainly evenly distributed in the cortex. Aggregates of radioactive particles in the large intestine indicate unabsorbed tartrate. At 24 h after the last dose of L(+)-tartrate, only localization of radioactivity in bone was detected and persisted for at least 192 h after the last dose.
At 3 h after the last dose of DL-tartrate, the radioactivity was mainly present in the gastrointestinal tract, liver, kidneys and bone. Aggregates of radioactive particles were present in kidney cortex and medulla. the aggregates in kidney could be detected for at least 192 h after the last dose. Radioactivity was associated with bone throughout the time-course studied.
Concentrations of radioactivity associated with bone after the last dose of L(+)-tartrate were maximal at 1 h (787 μg/g) and declined slowly. For DL-tartrate, it was maximal at 12 h (1203 μg/g) and declined rapidly. During 96 h after the last dose, concentrations of radioactivity in the bones of rats dosed with DL-tartrate was twice those in the bones of rats dosed with L(+)-tartrate.
The retention of radioactivity in the kidneys of rats dosed with L(+)-tartrate was much less than in those of rats dosed with DL-tartrate. Furthermore, radioactivity in the kidney of rats dose L(+)-tartrate was mainly water soluble whereas that of rats dose with DL-tartrate was probably present as the more insoluble calcium salt.

Toxicokinetic parameters

Toxicokinetic parameters 1

Test no.:

#1

Toxicokinetic parameters:

half-life 1st: 3 h in plasma after the last dose

Toxicokinetic parameters 2

Test no.:

#1

Toxicokinetic parameters:

half-life 2nd: 53 h in plasma after the last dose

Metabolite characterisation studies

Metabolites identified:

no

Any other information on results incl. tables

The retention of radioactivity in the kidneys of rats dosed with L(+)-tartrate was much less than in those of rats dosed with DL-tartrate. And furthermore, L(+)-tartrate in kidneys was mainly in soluble manner, whereas DL-tartrate was present as more insoluble calcium salt.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
At 3 h after the last dose of L(+)-tartrate, the radioactivity was mainly present in the gastrointestinal tract, liver, kidneys and bone. L(+)-[14C] tartrate was not retained in the kidneys (1287±118 ppm at 6 h, n = 8) when administered to rats for 7 days at a dose level of 2.73 g/kg/day, and the initial decline of plasma concentrations of radioactivity was more rapid (t0.5 approx.3 h). For this reason, monosodium L (+)-tartrate was non-toxic at 2.73 g/kg/ day whereas monosodium DL-tartrate was toxic at this dosage.

Executive summary:

This study reported were carried out to compare the distribution of radioactivity in the bones and kidneys of rats administered relatively high repeated oral doses of monosodium L(+)-[14C]tartrate or DL-[14C]tartrate. At 3 h after the last dose of L(+)-tartrate, the radioactivity was mainly present in the gastrointestinal tract, liver, kidneys and bone.  L(+)-[14C] tartrate was not retained in the kidneys (1287±118 ppm at 6 h, n = 8) when administered to rats for 7 days at a dose level of 2.73 g/kg/day, and the initial decline of plasma concentrations of radioactivity was more rapid (t0.5approx.3 h). For this reason, monosodium L (+)-tartrate was non-toxic at 2.73 g/kg/ day whereas monosodium DL-tartrate was toxic at this dosage.