Iron(3+) ion dipotassium 2-({2-[bis(carboxylatomethyl)amino]ethyl} (carboxylatomethyl)amino)acetate; hydrate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was not peformed according to guideline or GLP. No data on test substance composition or purity.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Iron Absorption by Humans and Swine from Fe(lll)-EDTA. Further Studies

Author:

Candela E, Camacho MV, Martinez Torres C, Perdomo J, Mazzarri G, Acurero G, Layrisse M

Year:

1984

Bibliographic source:

J Nutr 114(12): 2204-2211.

Materials and methods

Objective of study:

other: aboroption and excretion

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium feredetate

EC Number:

239-802-2

EC Name:

Sodium feredetate

Cas Number:

15708-41-5

Molecular formula:

C10H12N2O8FeNa

IUPAC Name:

Sodium; 2-[2-(bis(carboxylatomethyl)amino)ethyl-(carboxylatomethyl)amino]acetate; iron(+3) cation

Details on test material:

Fe(III)-EDTA

No further details.

Radiolabelling:

yes

Test animals

Species:

pig

Strain:

other: Yorkshire-Hampshire

Sex:

male

Administration / exposure

Route of administration:

oral: capsule

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

single dose

Doses / concentrations

Remarks:

Doses / Concentrations:
36 mg

No. of animals per sex per dose / concentration:

16 males

Control animals:

no

Results and discussion

Preliminary studies:

Not applicable

Main ADME results

Type:

other: absorption and excretion

Results:

see table

Toxicokinetic / pharmacokinetic studies

Details on absorption:

The examination of the absorption of the 14C-labeled EDTA complex reveals that about 5% is absorbed by the mucosa from the pylorus up to 9 m of the jejunum, trans ferred very slowly from the mucosa to the plasma, and then eliminated by the kidney.

About 5% of the 55Fe is split from the EDTA complex in the lumen of the gut, absorbed mainly by the mucosa of the stomach (pylorus) and the upper jejunum, then transferred to plasma transferrin and finally incorporated into hemoglobin.

Details on excretion:

Approximately 5.4% of the administered dose is excereted in the urine. About 80% of the 14C administered is found in the soluble fraction of the feces and 20% in the precipitate.

Only a small proportion of the iron ab sorbed is excreted by the kidney. The 55Fe activity found in the soluble and insoluble fractions of stool apparently indicate that a large proportion of the iron (about 92% of the dose adminis tered) is split from EDTA, and precipitated as an insoluble compound, then eliminated via the feces.
Only a small proportion of the iron administered (about 3%) remains soluble, possibly still bound to EDTA. These data only show the distribution of soluble and insoluble iron in stool, that is, at the last stage of digestion.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
This study showed that 14C labelled NaFe(III)EDTA is poorly ( ± 5%) and slowly absorbed to the plasma and excreted by the kidney within 48 hours.
The rest of the 14C was excreted in the feces, about 80% in a soluble form and 20% in the insoluble fraction.

Executive summary:

Studies on iron absorption from Na⁵⁹Fe-EDTA in humans have shown that only a small proportion of the iron absorbed is excreted by the kidney, less than 1% of the dose administered. The pathway of Na⁵⁵Fe-[2-14C]EDTA absorption and excretion when administered orally was studied in swine. A certain proportion (about 5% ) of the⁵⁵Fe is split from the EDTA complex in the lumen of the gut, absorbed mainly from the pylorus and upper jejunum, transferred to plasma transferring and then incorporated into the circulating hemoglobin. A small proportion of the iron absorbed, less than 1% of the dose administered, is excreted by the kidney, to a degree similar to that excreted by humans. The rest of the iron is eliminated in the feces; about 3% in a soluble form possibly still bound to EDTA and the greater part, about 92%, in an insoluble form. About 5% of the¹⁴C is absorbed almost uniformly along the pyloric duodenal and jejunal mucosa, then transferred slowly to the plasma and excreted by the kidney within 48 hours. The rest of the¹⁴C was excreted in the feces, about 80% in a soluble form and 20% in the insoluble fraction.