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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Documentation insufficient for assessment For read-across justification refer to section 13.

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 in 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 conducted on female animals. Studies were made after intraperitoneal, intravenous, intramuscular, and oral administration (intubation).
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- no further data available
Radiolabelling:
yes
Remarks:
14C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 200 - 250 g

Administration / exposure

Route of administration:
other: ip, iv, im and oral (gavage)
Vehicle:
water
Duration and frequency of treatment / exposure:
single dose
Doses / concentrations
Remarks:
Doses / Concentrations:
50 mg/kg bw
(additionally one study was performed using 250 mg/kg bw for ip application)
No. of animals per sex per dose:
no data
Control animals:
no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Oral studies:
2-18% (most of the values were 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% of the dose was excreted in the urine
- 80-95% of the dose was excreted via feces within 24 h
- less than 0.1% of the dose was exhaled as CO2

PARENTERAL ADMINISTRATION
- 95 - 98% of the dose appeared in the urine within 6 h (iv: 96.09%; ip: 98.67%; im: 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 parametersopen allclose all
Toxicokinetic parameters:
half-life 1st: 32 min (half-live urine; im application)
Toxicokinetic parameters:
half-life 1st: 31 min (half-live urine; iv application)
Toxicokinetic parameters:
half-life 1st: 35 min (half-live urine; ip application)
Toxicokinetic parameters:
half-life 1st: no data (half-live urine; 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

- While the half-life determine in urine was 31 to 35 min after parenteral application, a 50% drop of activity in plasma took 35- 50 min.

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

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no bioaccumulation potential based on study results