Sodium [N-[2-[bis(carboxymethyl)amino]ethyl]-N-(2-hydroxyethyl)glycinato(4-)]ferrate(1-)

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:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Publication. Fairly well reported human study. Prior to GLP.

Data source

Reference

Reference Type:

publication

Title:

Metabolism of chelating agent diethylenetriamine pentaacetic acid (C14 DTPA) in man

Author:

Stevens E, Rosoff B, Weiner M, Spencer H

Year:

1962

Bibliographic source:

Proc. Soc. Exp. Biol. Med., Vol. 111, 235-238

Materials and methods

Objective of study:

other: Absorption and excretion

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Intravenous and oral dosing of radiolabelled test material was used to assess absorption, metabolism and excretion kinetics in man.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

EC Number:

200-652-8

EC Name:

N-carboxymethyliminobis(ethylenenitrilo)tetra(acetic acid)

Cas Number:

67-43-6

IUPAC Name:

N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine

Constituent 2

Reference substance name:

DTPA acid

IUPAC Name:

DTPA acid

Details on test material:

C14 labelled DTPA obtained from Geigy Chemical Corp.
dissolved in NaOH to form the sodium salt.
Specific activity not given.

Radiolabelling:

yes

Remarks:

C14 DTPA

Test animals

Species:

human

Sex:

not specified

Administration / exposure

Route of administration:

other: Intravenous and oral

Vehicle:

water

Details on exposure:

Intravenous: 10-15mg C14 DTPA with an activity of 15 to 20 micro curies
Oral: 3mg DTPA with an activity of 5-10 micro curies, or 50mg DTPA with and activity of 75-100 microcuries.

Duration and frequency of treatment / exposure:

Single treatments either orally or intravenously were administered to 7 volunteers (oral) and 4 volunteers (intravenous)

Results and discussion

Any other information on results incl. tables

Intravenous adminsitration:

The kidney was found to be the main pathway for DTPA excretion. 30 to 40% of the dose was excreted within 2 hours in the urine, 50 - 70% after 4 hours and an additional 15 to 20% in the following 4 hours. At the end of 24 hours 90 to 100% of the administered dose had been excreted via the urine. Analysis of the stool did not reaveal any radiolable indicating that the feaces is not a significant route of elimination for systemically administered DTPA.

Plasma levels of the C14 lable averaged 10% at 1 hour following the dose and rapidly decreased thereafter. No radioactivity could be detected in the plasma at 2 hours.

Oral administration:

The major portion of the DTPA appears to have been eliminated via the feaces, with between 95 and 100% recovered in the stool within 2 to 5 days. Urinary excretion was less than 3% in 4 of the patients and between 3 and 8% in the remaining 3 patients, averaging about 5%.

Blood samples did not reveal the presence of any radioactivity at any time point (1 hour to 3 days).

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
This study demonstrates that the major elimination route for systemically available DTPA is via the kidneys. Excretion via the urine is very rapid, occuring within 24 hours with a half life of approximately 2 hours. There is little to no elimination via the faeces following systemic dosing.
Following oral adminsitration the excretion of DTPA is almost exclusively via the faeces with less than 5% absorbed and subsequently excreted via the urine. The passage of the DTPA through the gut avries between individuals, however there is almost complete excretion of the chelant within 5 days of administration.