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Toxicological information

Exposure related observations in humans: other data

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Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
key study
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 Ethylenediaminetetraacetic Acid in Human Beings
Author:
Foreman & Trujillo
Year:
1954
Bibliographic source:
J. Lab. and Clin. Med. 43; 566-571 (1954)

Materials and methods

Endpoint addressed:
basic toxicokinetics
dermal absorption
GLP compliance:
no

Test material

Constituent 1
Chemical structure
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
Specific details on test material used for the study:
RADIOLABELLING INFORMATION
- Specific activity (of the radialabelled form): 2.5 x 10^7 d/min

Method

Ethical approval:
not specified
Details on study design:
- 3 young healthy adult male were used in each application group
Details on exposure:
INTRAVENOUS ADMINISTRATION
- Dose preparation:
2.2 mg of 14C-CaNa2EDTA was mixed with 2 g of unlabelled CaNa2EDTA in a total of 10.5 mL water
- Application:
injections were given over a 2-3 min period
- Sample taking:
blood samples: up to 6 h regularly exact time points not stated; urine: over a 24 h period as voided until radioactivity had fallen below detection levels; in one case spinal fluid
- Additional measurements:
blood pressure and electrocardiogram tracings were made every 15 min, starting 1/2 h before the administration and continuing for 1 h after

INTRAMUSCULAR ADMINISTRATION
- Dose preparation:
2.2 mg of 14C-CaNa2EDTA was mixed with 2 g of unlabelled CaNa2EDTA and 2 mL of a 1% procaine solution, all made up to 10 mL with water
- Application:
Injections were made into the buttocks, 5 mL each side
- Sample taking:
blood samples: up to 6 h regularly exact time points not stated ; urine: over a 24 h period as voided until radioactivity had fallen below detection levels

ORAL ADMINISTRATION
- Dose preparation:
1.5 mg of 14C-labelled CaNa2EDTA was dissolved in 1/2 mL water given in a gelatin capsule
- Sample taking:
Urine and feces were collected for the study (sample takings not specified); blood was collected in the first study only

SKIN ABSORPTION
- Dose preparation:
2 mg 14C-labelled CaNa2EDTA and 1 g unlabelled CaNa2EDTA were prepared in a thin paste of Aquaphor. In one study Na salt of EDTA was used instead of Ca salt.
-Application:
The past was spread over an area of 100 cm2 on a sheet of thin latex and taped firmly to the lateral chest wall. It was kept there for 24 h
-Sample taking:
Urine samples were taken

Results and discussion

Results:
INTRAVENOUS ADMINISTRATION
- Recovery in urine: 98.1 ± 4.6 %
- 50 % was excreted within 1 h, 90 % within 7 h
- Half-life blood clearance: 1 h 5 min
-Activity in spinal fluid 1 h after injection: 1/20 of the plasma
INTRAMUSCULAR ADMINISTRATION
- Recovery in urine: 98.8 ± 1.6 %
- 50% was excreted within 2.5 h, 90% within 7 h
- Half-life blood clearance: 1.5 h
ORAL ADMINISTRATION
- TS is poorly absorbed
- no TS could be detected in the blood
- 91 ± 2 % are excreted via feaces, 4.2 ± 2 % via urine
- TS is excreted within 72 h
SKIN ABSORPTION
- The maximum activity detected in urine was 0.001 %

Any other information on results incl. tables

- The study indicates that CaNa2EDTA passes through the body unchanged and is excreted via the kidney by both glomerular filtration and tubular excretion.

- The turnover time from the blood is approximately 1 h after iv administration.

- It is poorly absorbed from the GI-tract

- It does not penetrate the skin

Applicant's summary and conclusion