Tris[oxalate(2-)]dicerium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 September 2012 - 25 October 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted to GLP in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tris[oxalate(2-)]dicerium

EC Number:

205-362-5

EC Name:

Tris[oxalate(2-)]dicerium

Cas Number:

139-42-4

Molecular formula:

C6Ce2O12

IUPAC Name:

4,4'',5,5''-tetraoxo-1',4'-dihydro-1λ³,1''λ³,3λ³,3''λ³-dispiro[1λ³,3λ³-dioxa-2-ceracyclopentane-2,5'-1λ³-oxa-3λ³-oxa-2-ceracyclopenta[4,5-d]1λ³-oxa-3λ³-oxa-2-ceracyclopentane-2',2''-[1λ³,3λ³]dioxa-[2]ceracyclopentane]-2',2',2',2,2,2-hexakis(ylium)-1',4',1,1'',3,3''-hexaide

Test material form:

solid: crystalline

Details on test material:

Description: White crystalline solid
Storage conditions: Room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: RccHan:WIST
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: The bodyweight variation did not exceed ± 20 % of the bodyweight of the initially dosed animal.
- Fasting period before study: The animals were fasted overnight immediately before dosing and for approximately three to four hours after dosing.
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum access to mains drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): lighting was controlled by a time switch to give twelve hours continuous light (0600 to 1800) and twelve hours darkness.

IN-LIFE DATES: From: 25 September 2012 To: 25 October 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: Dimethyl sulphoxide was used as the test material did not dissolve or suspend in distilled water or arachis oil BP.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 female animals were dosed.

Control animals:

no

Details on study design:

SIGHTING STUDY
In the absence of data regarding the toxicity of the test material, 300 mg/kg was chosen as the starting dose.
A single female animal was treated at a dose level of 300 mg/kg (concentration 30 mg/mL, dose volume 10 mL/kg). No toxicity was observed.
In the absence of toxicity at a dose level of 300 mg/kg, an additional female animal was treated at 2000 mg/kg.

MAIN STUDY
No toxicity was observed in the animal treated at 2000 mg/kg, therefore a further four animals were treated, bringing the number treated at this dose level to 5.
All animals were dosed once by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose level to confirm the survival of the previously dosed animals.

- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Clinical observations were made 0.5, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily. Individual bodyweights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes. At the end of the observation period, the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:

In the single animal dosed at 300 mg/kg, no mortality was observed and no signs of systemic toxicity were present. The animal showed expected bodyweight gain throughout the observation period. No abnormalities were detected at necropsy.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period

Gross pathology:

No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight and as such the test material is not classified in accordance with EU criteria.

Executive summary:

The acute oral toxicity of the test material was assessed in the Wistar strain rat in accordance with the standardised guidelines OECD 420 and EU Method B.1 bis.

In the absence of toxicological information, a single fasted female was dosed at 300 mg/kg bw. In the absence of toxicity, a further sighting test was conducted by administering a dose of 2000 mg/kg to one fasted female. Following this, a further group of four fasted females was given a single oral dose of the test material as a suspension in dimethyl sulphoxide at a dose level of 2000 mg/kg bodyweight.

No mortality or signs of systemic toxicity were seen throughout the study. All animals showed expected gains in bodyweight and no abnormalities were noted at necropsy.

Therefore, under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bodyweight.