Disodium dihydrogen ethylenediaminetetraacetate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

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:

The Metabolism of 14C Labeled Ethylenediamine Tetraacetic Acid in the Rat

Author:

Foreman, H. et al.

Year:

1953

Bibliographic source:

J. Biol. Chem. 203, 1045-1053 (1953)

Materials and methods

Objective of study:

absorption

excretion

metabolism

toxicokinetics

Principles of method if other than guideline:

Metabolism studies were conducted on the rat. First distribution and balance studies were carried out with male animals. The animals were housed individually in metabolism cages for the separate collection of expired CO2, urine and feces. In a second series of experiments detailed studies on blood and urine were made on female animals. Studies were made after intraperitoneal, intravenous, intramuscular, and oral administration (intubation).

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

Test material form:

solid

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 250 g

Administration / exposure

Route of administration:

other: i.p., i.v., i.m. and oral

Vehicle:

water

Duration and frequency of treatment / exposure:

single dose

Doses / concentrations

Dose / conc.:

50 mg/kg bw (total dose)

Remarks:

(additionally one study was performed using 250 mg/kg bw for i.p. application)

No. of animals per sex per dose / concentration:

no data

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Oral studies: 2-18 % (most of the value in the range of 2-4 %)

Details on distribution in tissues:

No organ retained more than 0.5 % of the dose.

Details on excretion:

ORAL
- 2-18 % are excreted in the urine
- 80-95 % are excreted via feces within 24 h
- less than 0.1 % of the dose is exhaled as CO2

PARENTERAL ADMINISTRATION
- 95 - 98 % dose appeared in the urine within 6 h (i.v.: 96.09 %; i.p.: 98.67 %; i.m.: 95.35 %)
- less than 0.1 % of the dose was exhaled as CO2
- the dose size 250 mg/kg bw vs 50 mg/kg bw had no effect on the excretion kinetics
(see table 1)

Toxicokinetic parameters

Toxicokinetic parameters 1

Toxicokinetic parameters:

half-life 1st: 32 min (i.m. application)

Toxicokinetic parameters 2

Toxicokinetic parameters:

half-life 1st: 31 min (i.v. application)

Toxicokinetic parameters 3

Toxicokinetic parameters:

half-life 1st: 35 min (i.p. application)

Toxicokinetic parameters 4

Toxicokinetic parameters:

half-life 1st: no data (oral)

Metabolite characterisation studies

Details on metabolites:

Chromatography provided evidence that EDTA is not metabolized but passes the body unchanged.

Any other information on results incl. tables

Table 1: Distribution of 14C activity following administration of Ca C14-EDTA to rats

	time after ip administration			oral administration
Tissue sample	1.5 h	6 h	24 h	24 h
Urine	85.2	95.7	94.6	10.3
Feces	0.5	2.0	3.6	88.3
Expired CO2		0.05	0.08
Skin	2.3	0.8	0.3	0.16
Kidney	1.4	0.3	0.3	0.04
GI tract	0.2	0.2	0.7	0.45
Liver	0.5	0.2	0.05	0.18
Skeleton		0.3	0.1	0.08
Muscle		0.1	0.3	0.36
Blood	1.7	0.1	0.01	0.04
Remains	8.1	0.03	0.01	0.03