Zirconium dichloride oxide

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

no data

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

A Klimisch 3 score is assigned because there is 1. no guideline reported, 2. no data on substance origin and purity, 3. no data on origin of animals and acclimation period for animals, 4. no data on controls, 5. no information whether or not animals were fastened the day before dosing.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Toxicité et pharmacocinétique de l'oxychlorure de zirconium chez la souris et chez le rat

Author:

Delongeas JL, Burnel D, Netter P, Grignon M, Mur JM, Royer RJ, Grignon G

Year:

1983

Bibliographic source:

J. Pharmacol (Paris) 1983, 14, 4, 437-447

Materials and methods

Principles of method if other than guideline:

Single dose administration of zirconium oxychlorure diluted in distilled water.
Dose of 1.5 g ZOC/kg for mouses, doses of 5.3 g ZOC/Kg and 3 g/kg for rats.
Series of 12 mouses are then sacrified after 30 min, 1h, 2h, 3h, 4h, 6h, 8h, 18h, 24h, 48h and 72h.
Series of 3 rats are then sacrified after 30 min, 1h, 2h, 3h30, 6h (Dose of 5.3 g/kg).
Series of 3 rats are then sacrified after 30 min, 1h, 3h, 6h, 24h, 72h (Dose of 3 g/kg).

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Zirconium dichloride oxide

EC Number:

231-717-9

EC Name:

Zirconium dichloride oxide

Cas Number:

7699-43-6

Molecular formula:

Cl2OZr

IUPAC Name:

Dichloro(oxo)zirconium

Details on test material:

Zirconium oxychlorure PROLABO

Radiolabelling:

no

Test animals

Species:

other: mouse & rat

Strain:

other: Swiss & Wistar

Sex:

not specified

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Duration and frequency of treatment / exposure:

Single administration

Doses / concentrations

Remarks:

Doses / Concentrations:
1.5 g ZOC/kg (0.425 g Zr/kg) to mouse (mouse of 25 g) - 37.5 mg ZOC / 10.6 mg Zr
5.3 g ZOC/kg (1.5 g Zr/kg) & 3 g/kg (0.85 g Zr/kg) to rat (rat of 150 g) - 795 mg ZOC / 225 mg Zr and 450 mg ZOC / 128 mg Zr

No. of animals per sex per dose / concentration:

11 series of 12 mouses (131)
5 series of 3 rats (15) for the 1.5 g Zr/kg dose
6 series of 3 rats (18) for the 0.85 g Zr/kg dose

Control animals:

no

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After administration zirconium oxychlorure passes the digestive barrier as it is found in blood.
For mice the maximal concentration in blood is after 6 h and is 2.9 mg Zr/L blood or 10.15 mg ZOC/L blood. For a mouse having approximately 2 mL of blood, 0.02 mg of ZOC were bioavailable after 6 hours so around 0.05% of the substance administered.

For the rats at the dose of 0.850 g Zr/kg, the maximal concentration in blood is after 6 hours and is 1.15 mg Zr/L blood or 4.025 mg ZOC/L blood. For a rat having approximately 7 mL of blood, 0.03 mg of ZOC were bioavailable after 6 hours so around 0.007% of the substance administered.
For the rats at the dose of 1.5 g Zr/kg the maximal dose in blood is after 3h30 and is 3.4 mg Zr/L blood or 12 mg ZOC/L blood. For a rat having approximately 7 mL of blood, 0.084 mg of ZOC were bioavailable after 6 hours so around 0.01% of the substance administered.

Details on distribution in tissues:

Bones, liver, kidneys, lungs, ovaries and CNS were analysed for zirconium. Zirconium is predominantly found in the ovaries and in the lungs. It is also found in bones and in a lower degree in the CNS.

Details on excretion:

After administration, fecal elimination is important, 88 to 97% of the administered zirconium is found in the feces after 24 hours. Less than 0.001% is found in the feces between 24h and 72h after administration of the substance.
Elimination via urinary tract is unimportant (0.001%). Nevertheless the concentration eliminated via urinary tract is more important after 72h than after 24h.

Metabolite characterisation studies

Metabolites identified:

not specified

Applicant's summary and conclusion

Conclusions:

In this study, mice and rats were administered zirconium dichloride oxide in water via oral gavage. Absorption in the blood is limited and the maxima (after 6 h) varied between 0.007 and 0.05% of the administered dose.
Because the substance is hardly absorbed in the GI tract it is predominantly excreted via the feces. From the small portion absorbed, part of it is released via the urinary tract (6% after 24h - 20% after 72h).
The small absorbed fraction is distributed and fixed in the ovaries, liver and lung, and to a lesser degree in bone and CNS.