Hexakis[μ-(acetato-O:O')]-μ3-oxo-triangulo-triruthenium acetate

Endpoint summary

Description of key information

In a guideline study, to GLP, the acute oral LD50 of ruthenium acetate was determined to be greater than 2000 mg/kg bw (Allen, 1995a).

In a guideline study, to GLP, the acute dermal LD50 of ruthenium acetate was determined to exceed 2000 mg/kg bw , as no deaths occurred at this limit dose (Sanders, 2004).

No relevant acute inhalation toxicity data were identified.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06-Nov-1995 to 06-Dec-1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 401)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(deleted 17-Dec-2002)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

(now obsolete)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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
- Source: Charles River (UK) Ltd., Margate, Kent

- Age at study initiation: 5-8 weeks

- Weight at study initiation: Males 150-167 g, females 138-160 g

- Fasting period before study: Yes, overnight

- Housing: Solid-floor polypropylene cages with wood flakes

- Diet (e.g. ad libitum): Rat and mouse expanded diet no. 1, ad libitum

- Water (e.g. ad libitum): Mains drinking water, ad libitum

- Acclimation period: >=5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22

- Humidity (%): 46-59

- Air changes (per hr): ~15

- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 06-Nov-1995 To: 06-Dec-1995

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml

- Amount of vehicle (if gavage): 10 ml/kg bw

- Justification for choice of vehicle: none stated, but well-known vehicle


- Purity: not stated, but distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

Single dose: 2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
- Observation for deaths or overt signs of toxicity: 0.5, 1, 2 and 4 hours after dosing, then once daily for 14 days
- Body weights: days 0, 7 and 14 of the study

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs (overt signs of toxicity and behavioural and clinical observations) and body weight

Statistics:

An estimate of the acute oral medial lethal dose (LD50) was made using mortality data from the study

Preliminary study:

1 male and 1 female were dosed at 2000 mg/kg bw and observed for 5 days. As no toxicity was observed, a dose of 2000 mg/kg bw was selected for the main study.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths

Clinical signs:

other: No signs of systemic toxicity

Gross pathology:

No abnormalities

Other findings:

- Organ weights: not done

- Histopathology: not done

- Potential target organs: not done

- Other observations: not done

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, to GLP, the acute oral LD50 of ruthenium acetate in rats was >2000 mg/kg bw .

Executive summary:

Ruthenium acetate was tested for its acute oral toxicity in rats, according to OECD Test Guideline 401. Following a range-finding study in which no toxicity was observed at 2000 mg/kg bw, the main study was performed at this dose level (limit test). Sprague-Dawley rats (5/sex) were administered the test substance by gavage in water at 2000 mg/kg bw and subsequently observed for 14 days.

 

There were no deaths, no overt signs of toxicity, no effect on body weight and no abnormalities were seen at necropsy. The acute oral LD50 of ruthenium acetate in rats was >2000 mg/kg bw under the conditions of the test.

 

Based on the results of this study, the test item should not be classified for acute oral toxicity according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Overall, good-quality database which meets REACH Standard Information Requirements.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21-Jul-04 to 04-Aug-04

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

GLP compliance:

yes (incl. QA statement)

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
- Source: Charles River (UK) Ltd., Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: >=200 g, "the weight variation did not exceed +- 20% of the mean weight for each sex"
- Fasting period before study: no data
- Housing: 5/cage; solid floor polypropylene cages with woodflakes, "the animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study"
- Diet (e.g. ad libitum): Certified Rat and Mouse Diet (Code 5LF2), ad libitum
- Water (e.g. ad libitum): mains water, ad libitum
- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 20-70
- Air changes (per hr): >=15
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 14-Jul-04 To: 22-Jul-04

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Details on dermal exposure:

TEST SITE
- Area of exposure: not specified in cm2, but as 10% of total body surface area
- % coverage: 10
- Type of wrap if used: surgical gauze covered with self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with cotton wool moistened with arachis oil
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): moistened with vehicle
- Constant volume or concentration used: yes
- For solids, paste formed: no data, but described as being moistened with vehicle, rather than dissolved in it

VEHICLE
- Amount(s) applied (volume or weight with unit): sufficient to moisten the required weight of test material
- Concentration (if solution): no data, but used to moisten test material, rather than to dissolve it
- Lot/batch no. (if required): no data
- Purity: no data, but described as "arachis oil BP"

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- observervations - 0.5, 1, 2 and 4 hours after dosing, then once daily for 14 days
- body weight - days 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal reactions

Statistics:

not done

Preliminary study:

not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

no deaths

Clinical signs:

other: no signs of systemic toxicity

Gross pathology:

no abnormalities

Other findings:

- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: not examined
- Other observations:
- dermal reactions - grey-coloured staining at all treatment sites on day 1

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a guideline study, conducted to GLP, the acute dermal LD50 of ruthenium acetate in rats was found to exceed 2000 mg/kg bw .

Executive summary:

In an acute dermal toxicity test, conducted according to OECD Test Guideline 402 and to GLP, groups of 5 male and 5 female rats were dermally exposed to ruthenium acetate (moistened with arachis oil) for 24 hr (application to the shaved skin under semi-occlusion). Animals were observed at 0.5, 1, 2 and 4 hr after the start of exposure and then once daily over a 2-week period. There was no control group.

 

There were no deaths, clinical signs, gross pathological effects or indications of skin irritation in any of the animals. The acute dermal LD50 of ruthenium acetate is greater than 2000 mg/kg bw in rats.

 

Based on the results of this study, ruthenium acetate should not be classified for acute dermal toxicity according to EU CLP criteria (EU 1272/2008).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Overall, good-quality database which meets REACH Standard Information Requirements.

Additional information

No relevant human acute toxicity data were identified.

 

Ruthenium acetate was tested for its acute oral toxicity in rats, according to OECD Test Guideline 401. Following a range-finding study in which no toxicity was observed at 2000 mg/kg bw, the main study was performed at this dose level (limit test). Sprague-Dawley rats (5/sex) were administered the test substance by gavage in water at 2000 mg/kg bw and subsequently observed for 14 days. There were no deaths, no overt signs of toxicity, no effect on body weight and no abnormalities were seen at necropsy. The acute oral LD50 of ruthenium acetate in rats was >2000 mg/kg bw under the conditions of the test (Allen, 1995a).

 

In an acute dermal toxicity test, conducted according to OECD Test Guideline 402 and to GLP, groups of 5 male and 5 female rats were dermally exposed to ruthenium acetate (moistened with arachis oil) for 24 hr (application to the shaved skin under semi-occlusion). Animals were observed at 0.5, 1, 2 and 4 hr after the start of exposure and then once daily over a 2-week period. There was no control group. There were no deaths, clinical signs, gross pathological effects or indications of skin irritation in any of the animals. The acute dermal LD50 of ruthenium acetate is greater than 2000 mg/kg bw in rats (Sanders, 2004).

 

No acute inhalation toxicity data were identified, or are required.

Justification for classification or non-classification

Based on the results of the available reliable acute oral and dermal rat studies, hexakis[mu-(acetato-O:O')]-μ3-oxo-triangulo-triruthenium acetate / ruthenium acetate does not require classification for acute toxicity by the oral and dermal routes, according to EU CLP criteria (EC 1272/2008).

 

No clear evidence of specific target organ toxicity was noted. As such, classification for STOT-SE is not considered appropriate.