Registration Dossier

Toxicological information

Exposure related observations in humans: other data

Administrative data

Endpoint:
exposure-related observations in humans: other data
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles

Data source

Reference
Reference Type:
publication
Title:
The Metabolism of 14C Labeled Ethylenediaminetetraacetic Acid in Human Beings
Author:
Foreman, H. et al
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

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): CaNa2EDTA
- 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 CaNa2EDTAin 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