Ruthenium, dichloro[1,3-dihydro-4,5-dimethyl-1,3-bis(2,4,6-trimethylphenyl)-2H-imidazol-2-ylidene](2-thienylmethylene)(tricyclohexylphosphine)-, (SP-5-41)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-06-30 to 2016-09-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

adopted 17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

[1,3-bis(2,4,6-trimethylphenyl)-4,5-dimethylimidazol-2-ylidene](2-thienylmethylidene)(tricyclohexylphosphine)ruthenium(II)dichloride

Cas Number:

1190427-50-9

Molecular formula:

C46H65Cl2N2PRuS

IUPAC Name:

[1,3-bis(2,4,6-trimethylphenyl)-4,5-dimethylimidazol-2-ylidene](2-thienylmethylidene)(tricyclohexylphosphine)ruthenium(II)dichloride

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Wistar

Remarks:

WISTAR rats Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: animals no. 1 – 3: 11 - 12 weeks old; animals no. 4 – 6: 8 - 9 weeks old
- Weight at study initiation: animals no. 1 – 3: 171 – 187 g; animals no. 4 – 6: 152 – 161 g
- Fasting period before study: 16 to 19 hours

- Housing: group housing in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet (e.g. ad libitum): ad libitum, Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): ad libitum, tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: Step 1, animals no. 1 - 3: 07 June - 05 July 2016; Step 2, animals no. 4 - 6: 05 - 12 July 2016

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): 12 hours light, 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.2 g/ml
- Amount of vehicle (if gavage): 10 ml/kg.
- Justification for choice of vehicle: preparation with corn oil yielded a well applicable suspension, corn oil has non-toxic characteristics, test substance is insoluble in water
- Lot/batch no. (if required): Sigma-Aldrich, lot no. MKBV2080V


MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg body weight.

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: toxicity was not expected

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3 per step, 2 steps performed

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animal were examined once daily, on the day of dosing, examination was carried out several times (at least once during the first 30 minutes and special attention was given during the first 4 hours post-dose), animals were weighed on day 1 (prior to the administration), day 8 and day15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

not observed

Clinical signs:

other: no specific findings during the whole observation period

Gross pathology:

no specific gross pathological changes were recorded for any animal

Any other information on results incl. tables

Please see attached file for results.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

- A single oral application of the test item to rats at a dose of 2000 mg/kg body weight was not associated with signs of toxicity or mortality
- The median lethal dose of the test item after a single oral administration to female rats, observed over a period of 14 days is: LD50 cut-off (rat): 5000 mg/kg bw
- According to Annex I of Regulation (EC) 1272/2008, the test item has no obligatory labelling requirement for toxicity and is not classified.
- According to GHS (Globally Harmonized Classification System), the test item has no obligatory labelling requirement for toxicity and is not classified.

Executive summary:

A valid test for acute oral toxicity according to OECD Guideline and under GLP was carried out with the test substance and did not identify any signs of toxicity.