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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles For read-across justification refer to section 13.

Data source

Reference
Reference Type:
publication
Title:
Depletion of Essential Elements by Calcium Disodium EDTA Treatment in the Dog
Author:
Ibim SEM et al.
Year:
1992
Bibliographic source:
Toxicology 73; 229-237

Materials and methods

Objective of study:
other: Effects of CaNa2EDTA on the metabolism of Zn, Cu, Mn
Principles of method if other than guideline:
The effect of calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) on the metabolism of Zn, Cu and Mn was investigated in mongrel female dogs. Dogs received either CaNa2EDTA subcutaneously or 0.9% NaCl (controls). Urine was collected every 6 h. Tissue samples were obtained from liver, kidney, duodenum, muscle, hair, skin and bone post exsanguination.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Calcium disodium ethylenediaminetetraacetate (CaNa2EDTA)
- Preparation: disodium EDTA was mixed with equimolar quantities of CaCO3, in water and heated with constant stirring until excess CO2 was expelled and the final solution was adjusted to pH 7.4 with NaOH.
Radiolabelling:
no

Test animals

Species:
dog
Strain:
other: Mongrel
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Canine Control Center
- Diet: Purina Dog Chow (concentration of Zn, Cu or Mn was 1.25; 0.16; or 0.98 mg/g dry weight, respectively)
- Water: ad libitum
- Acclimation period: 3-4 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 25°C

Administration / exposure

Route of administration:
subcutaneous
Vehicle:
water
Duration and frequency of treatment / exposure:
54 h
Doses / concentrations
Remarks:
Doses / Concentrations:
280 mg/kg/6 h (original data: 0.75 mmol/kg/6 h)
No. of animals per sex per dose:
5
Control animals:
other: 0.9% sterile NaCl
Details on dosing and sampling:
- Body fluids sampled: urine; every 6 h
- Tissues sampled: liver, kidney, upper duodenum (upper small intestine), muscle (thigh), bone (femur), hair and skin.



Statistics:
Analysis of variance (ANOVA) and Duncan’s new multiple range test were used to test for differences between groups. Differences between means were tested by two-way unpaired Student’s t-test.

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on excretion:
- CaNa2EDTA to dogs caused a significant increase in urine flow when compared to controls

URINARY EXCRETION OF ZN
- significant increase in the excretion of Zn when compared to control (cumulative excretion within 54 h: 24.92 + /- 0.346 mg compared to 1.58 + /- 0.24 mg in the control)
- Maximal excretion of Zn occurred between 6 and 12 h of treatment (17% of total Zn)

URINARY EXCRETION OF CU
CaNa2EDTA treatment resulted in a significant increase in the excretion of Cu when compared to control (cumulative excretion within 54 h: 0.922 + /- 0.24 mg compared to 0.12 + /- 0.03 mg in the control)

URINARY EXCRETION OF MN
CaNa2EDTA treatment resulted in a significant increase in the excretion of Mn when compared to control (cumulative excretion within 54 h: 0.582 + /- 0.166 mg compared to 0.042 + /- 0.01 mg in the control)

Metabolite characterisation studies

Metabolites identified:
no

Any other information on results incl. tables

TISSUE LEVELS OF Zn, Cu AND Mn

- statistically significant decrease in the tissue levels of Zn (small intestine, hair and skin) and Mn (hair) when compared to controls

- statistically significant increase in the concentration of Cu in the kidney when compared to controls

Applicant's summary and conclusion