trans-cyclohexane-1,2-dinitrilotetraacetic acid

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Partitioning of Renal Zinc between Metallothionein and Ethylenediaminetetraacetic Acid (EDTA) after Treatment of Rats with Ca(Na)2EDTA

Author:

Miller, C.R. et al

Year:

1986

Bibliographic source:

Toxicology and Applied Pharmacology 84, 584-592 (1986)

Materials and methods

Objective of study:

excretion

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Rats were injected with a single dose of [14C]EDTA. The concentration of EDTA in urine and kidney homogenates was determined at several time points.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium calcium edetate

EC Number:

200-529-9

EC Name:

Sodium calcium edetate

Cas Number:

62-33-9

Molecular formula:

C10H12CaN2O8.2Na

IUPAC Name:

calcium disodium 2,2',2'',2'''-(ethane-1,2-diyldinitrilo)tetraacetate

Specific details on test material used for the study:

Specific activity (if radiolabelling): 5 µCi/100 mg

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

other: Charles River

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Weight at study initiation: 200 - 300 g
- Individual metabolism cages: yes
- Diet: NIH-31 rat food ad libitum
- Water: tap water ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

not specified

Duration and frequency of treatment / exposure:

single treatment

Doses / concentrations

Dose / conc.:

400 mg/kg bw (total dose)

No. of animals per sex per dose / concentration:

18

Control animals:

other: yes, 0.9% saline treated animals

Details on study design:

18 rats were each injected with a single dose of [14C]EDTA and placed in plastic metabolic cages for urine collection. Six were killed at 16, 22, or 28 hr after the injection. One control rat was killed at each time point. Kidneys were removed, weighed and homogenized. Radioactivity in the urine and kidney homogenates was measured by scintillation counting in order to calculate EDTA concentrations.

Details on dosing and sampling:

PHARMACOKINETIC STUDY
- Body fluids sampled: Urine
- Tissues sampled: Kidneys
- Time and frequency of sampling: urine: 16, 22, 28 h
- Method type for identification: Liquid scintillation counting

Statistics:

Student's t-test, ANOVA and Dunnett's test

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

- During the 22 h period, the renal EDTA concentration was about 80 µg/g kidney homogenate. This equals to 0.1-0.2% of the EDTA injected.

Details on excretion:

- By 22 hr, 80% + / - 3% of the injected dose had been collected in the urine. This amount stayed approximately the same until 28 h after application.

Metabolite characterisation studies

Metabolites identified:

not measured

Applicant's summary and conclusion

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results