Dipraseodymium dizirconium heptaoxide

Endpoint summary

Description of key information

There is no experimental study available on the acute oral toxicity of the substance dipraseodymium dizirconium heptaoxide. However, based on a weight of evidence approach including experimental results obtained for the constituents, i.e. praseodymium(III,IV) oxide and zirconium dioxide, it can be concluded that the substance has a LD50 > 2000 mg/kg bw and does not need to be classified for acute oral toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2 March 1994 - 4 May 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

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: approximately 6 weeks
- Weight at study initiation: 165 ± 7g for the males, 159 ± 6 g for the females
- Fasting period before study: 18 hours before treatment; food was replaced approximately 4 hours after treatment.
- Housing: The animals were housed in groups of 4 to 7 animals of the same sex in polycarbonate cages (48 x 27 x 20 cm) during the acclimatisation period and groups of 5 animals of the same sex during the study. Each cage contained graded, dust-free sawdust.
- Food consumption (e.g. ad libitum): ad libitum; AO4 C pelleted diet (U.A.R., 91360 Villemoisson-sur-Orge, France)
- Water consumption (e.g. ad libitum): ad libitum filtered water contained in bottles
- Acclimation period: 5 days during which they were observed daily
- Source: Iffa Crédo, 69210 L'Arbresle, France

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 50 ± 20 % relative humidity
- Air changes (per hr): 13 cycles/hour of non-recycled and filtered air
- Photoperiod (hrs dark / hrs light): 12hr/12hr

In-life dates: From 02 to 16 March 1994

Route of administration:

oral: gavage

Vehicle:

other: aqueous solution of methylcellulose at 0.5 %

Details on oral exposure:

VEHICLE
The vehicle used was an aqueous solution of methylcellulose at 0.5 % (batch No. 73H0365 Prolabo, 75526 Paris, France).
Water for injections (batch No. 7860 Biosédra, 92240 Malakoff, France).

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION
On the day of the treatment, the test material was ground using a mortar and pestle, then was suspended in the vehicle.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

DETAILS ON STUDY DESIGN
- Duration of observation period following administration: 14 days
- Frequency of observations: The animals were observed frequently after administration of the test material and at least once a day for clinical signs and at least twice a day for mortality.
- Frequency of weighing: Animals were weighed just before administration of the test material and then on days 5, 8 and 15. The body weight of the animals treated with the test material was compared to laboratory historical control data for animals dosed by the oral route.
- Necropsy of survivors performed: yes (day 15)
- Other examinations performed: macroscopic examination at necropsy (digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities)

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occured during the observation period.

Clinical signs:

other: No clinical signs were observed during the study.

Gross pathology:

The macroscopic examination of the main organs of the animals sacrificed at the end of the study revealed no apparent abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the experimental conditions of this study, the oral LD50 of the test material was > 2000 mg/kg in rats. No signs of toxicity were observed at this dose and the test material requires no classification in accordance with EU criteria.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2008-01-16 to 2008-04-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

However, 6 animals were dosed at once rather than dosing in steps with 3 animals per step.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Certificate provided by Groupe Interministeriel Des Produits Chimiques

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle, France)
- Age at study initiation: 8 weeks old
- Weight at study initiation: between 188 g and 207 g
- Fasting period before study: 1 day
- Housing: Three healthy female rats were kept in solid-bottomed clear polycarbonate cages with a stainless steel mesh lid.
- Diet: foodstuff provided ad libitum; food was removed at D-1 and then redistributed 4 hours after the test item administration.
- Water: tap-water from public distribution system provided ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22 degree C
- Humidity (%): 39 and 55%
- Air changes (per hr): not applicable
- Photoperiod (hrs dark / hrs light): 12 hours daily

IN-LIFE DATES: From: 2008-02-05 To: 2008-02-20

Route of administration:

oral: gavage

Vehicle:

other: distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight

DOSAGE PREPARATION (if unusual): The animals of the treated group received an effective dose of 2000 mg/kg body weight of the test item, diluted in distilled water and administered by gavage under a volume of 10 mL/kg body weight using a suitable syringe graduated fitted with an oesophageal metal canula.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 female rats

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were weighed on D0 (just before administering the test item), then on D2, D7, and D14.
Weight changes were calculated and recorded.
- Necropsy of survivors performed: yes; Only those organs likely to be modified in cases of acute toxicity were examined. Those presenting macroscopic anomalies can be removed and preserved in view of microscopic examinations.
- Other examinations performed: Systematic examinations were carried out to identify any behavioural or toxic effects on the major physiological functions 14 days after administration of the test item.
Observations and a mortality report were then carried out every day for 14 days.

Statistics:

no data

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality occurred during the study.

Clinical signs:

other: No clinical signs related to the administration of the test substance were observed.

Gross pathology:

The macroscopic examination of the animals at the end of the study did not reveal treatment-related changes.

Other findings:

no data

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of CC10 Zirconium Oxide is higher than 5000 mg/kg body weight by oral route in the rat.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

weight of evidence

Justification for type of information:

Read across from studies performed with praseodymium(III,IV) oxide and zirconium dioxide. The read across justification document is attached in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: The substance dipraseodymium dizirconium heptaoxide is expected to have a LD50 value of > 2000 mg/kg bw and therefore does not need to be classified for acute oral toxicity.

Remarks:

This conclusion is based on data obtained with the oxides of the substance, i.e. praseodymium(III,IV) oxide and zirconium dioxide. For praseodymium(III,IV) oxide a LD50 value of > 2000 mg/kg bw was obtained whereas the key LD50 value for zirconium dioxide was > 5000 mg/kg bw. Therefore it can be concluded that the LD50 for the substance would be at least > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

1. Information on praseodymium(III,IV) oxide

For praseodymium(III, IV) oxide, the guideline study performed by Clouzeau (1994; Klimisch 1) resulted in an oral LD50 value > 2000 mg/kg bw in rats. No signs of toxicity were observed at this dose and hence, praseodymium(III,IV) oxide requires no classification in accordance with the CLP criteria.

2. Information on zirconium dioxide

For zirconium dioxide, the LD50 of CC10 Zirconium Oxide was found to be > 5000 mg/kg bw by oral route in rats in a guideline study (Phycher Bio Développement, 2008; Klimisch 1). No signs of toxicity were observed. Consequently, zirconium dioxide does not need to be classified for acute oral toxicity in accordance with the CLP criteria.

3. Conclusion on the substance dipraseodymium dizirconium heptaoxide

Since both constituents of the substance, i.e. praseodymium(III,IV) oxide and zirconium dioxide, did not cause any mortality or other adverse effects in rats at doses of 2000 or 5000 mg/kg bw, respectively, the LD50 of the substance can be expected to be at least > 2000 mg/kg bw and therefore the substance does not need to be classified for acute oral toxicity.

Justification for classification or non-classification

Based on experimental data available for its constituents praseodymium(III,IV) oxide and zirconium dioxide, the substance dipraseodymium dizirconium heptaoxide can be concluded not to be classified for acute oral toxicity.

Based on the results obtained in acute oral toxicity studies with the constituents of the substance (see above) as well as in vivo studies using dermal application of these constituents (in vivo skin irritation and skin sensitisation studies, see IUCLID Sections 7.3 and 7.4), it can be concluded that it is highly unlikely that the substance would need a classification for acute dermal toxicity.

No studies are available on the acute inhalation toxicity of the reaction mass. There are studies available on its constituents, however, these needed not to be included in this dossier, although these would lead to the conclusion that there is no need for classification of the substance for acute inhalation toxicity.