Zirconium tetranitrate

Endpoint summary

Description of key information

Oral LD50 = 4100 mg ZrO(CH3OO)2/kg bw, mortality was observed (Cochran, 1950)
Inhalation concentration of Zr >2≤ 3 mg/L, no mortality was observed (Mogilevskaya, 1968)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

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: Non-GLP non-guideline animal experimental study, limitations in design and/or reporting but nevertheless adequate for assessment

Principles of method if other than guideline:

In this acute oral toxicity study 24 adult Sprague Dawley rats (both sexes) were used. The animals received single 50% aqueous zirconyl acetate solutions orally by stomach tube. All animals were observed for ten days, but initial groups receiving a given compound were kept for thirty days to ascertain whether any significant mortality occurred after the tenth day. The LD50 values were obtained from ten day mortality data by using the log-probability method.

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adult rats
- Weight at study initiation: 200-300 gram
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
animals were maintained in air-conditioned rooms

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50% aqueous solution

Doses:

No details given.

No. of animals per sex per dose:

24 rats (no details on the number of males and females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: all animals were observed for 10 days, but initial groups receiving a given compound were kept for 30 days to ascertain whether any significant mortality occurred after the 10th day. It was found that 10-day observation periods were sufficient since animals either succumbed or recovered during this period.
- Other examinations performed: physiology and gross pathology

Statistics:

The LD50 values were obtained from ten day mortality data by using the log-probability method.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

4 100 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No sex differences were noted in the degree to which rats were susceptible to the substance investigated. LD50 values were therefore derived from the combined data on both sexes.

Mortality:

The time of death varied from a few hours to a few days following the administration of the compound. Few deaths however occurred later than five days after administration of zirconium salts.

Clinical signs:

other: Progressive depression and decrease in activity until death occurred.

Gross pathology:

No characteristic gross pathologic changes were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

4 100 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

General information

Water soluble zirconium salts like zirconium(tetra)nitrate, zirconium(di)acetate oxide or zirconium(tetra)acetate once in aqueous media dissociate very quickly at pH values of 4 to 9.5 forming the conjugate acid and hydrated forms of the insoluble ZrO2 (the most stable form of zirconium in water) (Daunderer, M.; Lehrbuch Klinische Toxikologie, 89. Erg. Lfg.; 11/94).

Due to the similar dissociation pattern it is concluded, that read across to other soluble zirconium salts is valid for the assessment of toxicological and ecotoxicological endpoints of zirconium(tetra)nitrate.

Tests with zirconium metal can be regarded as worst case scenario as dissociation of zirconium(tetra) nitrate will not lead to free zirconium metal in aqueous media.

Acute Oral Toxicity

In this acute oral toxicity test, 24 male and female Sprague Dawley rats were given a single oral dose of the read across substance zirconium(di)acetate oxide as a 50% aqueous solution by gavage. Animals were then observed for 10 days. Satellite groups were further kept for up to 30 days to ascertain whether any significant mortality occurred after the 10th day.

The time of death varied from a few hours to a few days following the administration of the compound. Few deaths however occurred later than five days after administration of the test substance. Animals showed progressive depression in activity until death occurred. There were no treatment related necropsy findings in any of the test animals. A LD50 of 4100 mg/kg bw was determined. The LD50 value was obtained from ten day mortality data by using the log-probability method.

This oral LD50 value is further supported by handbook data of another supporting substance stating a LD50 value of 4110 mg/kg bw for zirconium(tetra)acetate.

Acute Inhalation Toxicity

Because of the corrosive character of zirconium salts when getting in contact with humidity, the inhalation test was performed with zirconium dust in order to evaluate the actual systemic influence of the test substance.

In this acute inhalation toxicity test, white rats were exposed to doses of 2-3 mg/L zirconium dust via nose only two to three times. 5 animals per dose were tested. No mortality or clinical signs were observed. During necropsy organs did not reveal any alterations. In the lungs considerable pulmonary congestions were observed. Between dose levels of 2 to 3 mg/L no treatment related effects were observed when exposed to zirconium dust.

Conclusion

The acute oral limit test with zirconium(di)acetate oxide revealed no substance related findings during the course of the study. Furthermore no substance related mortality was observed after the tenth day of the study. Due to the similar dissociation pattern of zirconium tetranitrate compared to the read across substance and thus a similar metabolism when administered orally, it is concluded that zirconium tetranitrate is not acutely toxic. This conclusion is further underlined with the dissociation pattern of soluble zirconium salts in aqueous media. They dissociate quickly forming the conjugate acid and insoluble ZrO2 leading to a very low systemic availability and thus to a generally low toxicity.

The inhalation test with zirconium metal dust showed no systemic toxicity after inhaling 2 - 3 mg/L. But due to methodological defiencies like several administrations via nose only as well as lack of information regarding time of inhalation, exact concentration and analytical verification of the inhaled zirconium dust concentration, this test cannot be used for classification. It can only be used as supporting information showing that inhalation of 2 - 3 mg/L of the metal as such does not lead to any acute adverse effects in rats.

Justification for selection of acute toxicity – oral endpoint
Non-GLP and non-guideline animal experimental study, limitations in design and/or reporting but otherwise adequate for assessment

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available study on acute oral toxicity are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance does not need to be classified and labelled for acute oral toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EC. Considering the suitability of the available data, the test substance is not to be classified and labelled for acute inhalation toxicity.

 

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data on acute oral toxicity are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance does not need to be classified and labelled for acute oral toxicity under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation EC No 605/2014. Considering the suitability of the available data, the test substance is not to be classified and labelled for acute inhalation toxicity.