Tetraammonium decachloro-μ-oxodiruthenate(4-)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 Jan - 12 Feb 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Study conducted according to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

yes

Remarks:

Minor deviation: the dose level of 5000 mg/kg bw was administered as a volume of 20 ml/kg bw (concentration 250 mg/ml) as a concentration of 500 mg/ml 'was not applicable'

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tetraammonium-decachloro-µ-oxoruthenate (IV)

IUPAC Name:

Tetraammonium-decachloro-µ-oxoruthenate (IV)

Constituent 2

Reference substance name:

Tetraammonium decachloro-μ-oxodiruthenate(4-)

EC Number:

286-924-7

EC Name:

Tetraammonium decachloro-μ-oxodiruthenate(4-)

Cas Number:

85392-65-0

Molecular formula:

Cl10ORu2.4H4N

IUPAC Name:

tetraammonium decachloro-μ-oxodiruthenate(4-)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Tetraammonium-decachloro-µ-oxodiruthenate
- Molecular formula (if other than submission substance): (NH4)4Ru2Cl10O xH2O
- Substance type: technical product
- Physical state: Brown solid, earthy powder
- Analytical purity: Ru content 30.26 % w/w
- Impurities (identity and concentrations): NH4Cl (0.7% w/w), H2O (0.1% w/w) and metallic impurities (0.3% w/w); reported on the certificate of analysis in the study report.
- Composition of test material, percentage of components: 98.0% w/w chemical composition.
- Purity test date: 16 Nov 2015
- Lot/batch No.: 71495159
- Expiration date of the lot/batch: 21 April 2016.
- Stability under test conditions: no data
- Storage condition of test material: Store in a cool, dry place in tightly closed containers at 5 - 25oC. Avoid exposure to sunlight and high humidity.

Test animals

Species:

rat

Strain:

other: CD / Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany.
- Age at study initiation: Approx. 8 weeks
- Weight at study initiation: 170-205 g
- Fasting period before study: Approx. 16 hours.
- Housing: During the 14-day observation period the animals were kept individually in MAKROLON cages (type III plus). Granulated textured wood was used as bedding material for the cages, which were chaanged and cleaned twice a week. The rooms were lit and darked for 12 hour periods.
- Diet (e.g. ad libitum): Commercial ssniff® R/M-H V1534 produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum.
- Water (e.g. ad libitum): drinking water in bottles was offered ad libitum.
- Acclimation period: At least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25 (maximum range)
- Humidity (%): 40 - 70 (maximum range)
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 55, 175 and 250 mg/mL.
- Amount of vehicle (if gavage): 1.7-1.8 mL for the dose levels 550 and 1750 mg/kg bw; 3.6-4.2 mL for the dose level 5000 mg/kg bw.
- Justification for choice of vehicle: Not specified.
- Lot/batch no. (if required): MKBQ9948V, Sigma-Aldrich
- Purity: Not specified.

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw

- Rationale for the selection of the starting dose: Available information on two other ruthenium salts indicated an oral LD50 in rats between 595 and >2000 mg/kg bw. Thus the study was started with the Main Test at 550 mg/kg bw (from the sequence 1.75, 5.5, 17.5, 55, 175, 550, 1750 and 5000 mg/kg bw).

Doses:

550,
1750 or
5000 mg/kg bw

No. of animals per sex per dose:

1 (in the 550 mg/kg bw dose group); 3 (in the 1750 mg/kg bw dose group); 3 (in the 5000 mg/kg bw dose group).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. Body weights were recoded before administration and thereafter in weekly intervals up to the end of the study and at death.
- Necropsy of survivors performed: yes
- Observations: these included the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsies: macroscopic examination of dissected animals.

Statistics:

The LD50 value and the confidence interval were calculated using the software “AOT425statpgm (Version:1.0)”
[Acute Oral Toxicity (OECD Test Guideline 425) Statistical Programme (AOT 425 StatPgm). Version: 1.0, 2001.]

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

3 110 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 750 - <= 5 000

Mortality:

All 3 animals of the 5000 mg/kg bw dose group died within 4 days after administration (2 of them died within 2 days after administration). None of the animals of the 550 and 1750 mg/kg bw dose groups died prematurely.

Clinical signs:

Reduced motility, ataxia, reduced muscle tone, dyspnoea, piloerection and vocalization observed in 1 of 3 animals in the 5000 mg/kg bw dose group.

Body weight:

All surviving animals gained the expected body weight.

Gross pathology:

No pathological findings were noted at necropsy.

Other findings:

None.

Applicant's summary and conclusion

Interpretation of results:

other: No classification required under CLP

Conclusions:

In a OECD guideline study, to GLP, the acute oral LD50 value for tetraammonium decachloro-mu-oxodiruthenate was calculated to be 3110 mg/kg bw following gavage administration in female rats.

Executive summary:

The acute oral toxicity of tetraammonium decachloro-mu-oxodiruthenate was assessed in female rats, in a study carried out in accordance with OECD Test Guideline 425 and to GLP. Animals were treated by gavage with the test material (in corn oil) at doses of 550 (1 animal), 1750 (3 animals) or 5000 (3 animals) mg/kg body weight. Macroscopic examination was conducted on surviving animals.

There were no deaths, clinical signs, or effects on growth during the 14-day observation period for animals in the 550 and 1750 mg/kg bw dose groups. In the high dose group (5000 mg/kg bw) however, all 3 animals died within 4 days of administration of the test material and clinical signs of toxicity were apparent in one animal. There were no notable external or internal macroscopic findings upon necropsy in any of the treated animals.

The acute oral median lethal dose (LD50) of tetraammonium decachloro-mu-oxodiruthenate was calculated to be 3110 mg/kg bw using the Acute Oral Toxicity (OECD Test Guideline 425) Statistical Programme (AOT 425 Stat Pgm) software.

Based on the results of this study, the substance does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).