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

Endpoint summary

Description of key information

In a guideline study, to GLP, no irritation potential was observed when ruthenium acetate was applied (under occlusion for 4 hr) to the clipped, intact skin of three rabbits (Allen 1995b).

In a GLP eye irritation study, according to OECD guidelines, ruthenium acetate (0.1 g) produced severe eye irritation following instillation into the eye of a single rabbit (Allen, 1995c).

No relevant respiratory tract data were identified.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09-Nov-1995 to 12-Nov-1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 404)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(occlusive)

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

(occlusive)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK

- Age at study initiation: 12-16 weeks

- Weight at study initiation: 2.38-2.48 kg

- Housing: individually in suspended metal cages

- Diet (e.g. ad libitum): Stanrab SQC rabbit diet, ad libitum

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

- Acclimation period: >=5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-18

- Humidity (%): 56-65

- Air changes (per hr): ~15

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

IN-LIFE DATES: From: 09-Nov-1995 To: 12-Nov-1995

Type of coverage:

occlusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g

- Concentration (if solution): not applicable, crystalline solid moistened with water

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.5 ml

- Concentration (if solution): not applicable, solid test material moistened with water

- Lot/batch no. (if required): not applicable

- Purity: not stated, distilled water

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 6.25 cm2

- % coverage: not stated

- Type of wrap if used: cotton gauze patch (2.5 cm x 2.5 cm) secured with Blenderm (2.5 cm x 4.0 cm) (note: this is an occlusive tape), trunk wrapped in an elasticated Tubigrip corset

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, gentle swabbing with cotton wool soaked in distilled water, followed by 74% Industrial Methylated Spirits

- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize (erythema and eschar 0-4, oedema 0-4; primary irritation index calculated as total of scores for both endpoints, for both timepoints, for all 3 rabbits (12 values) divided by 6; classification according to Draize scheme)

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 24- and 72-hour timepoints combined

Score:

0

Max. score:

8

Reversibility:

other: not applicable

Irritant / corrosive response data:

No skin reactions (erythema or oedema) were seen at any timepoint (1, 24, 48 and 72 hours after removal of patches) in any of the 3 test animals; scores of 0.0 were recorded on each occasion giving a primary irritation index of 0.0

Other effects:

Faint green/black staining at all treatments sites

Interpretation of results:

GHS criteria not met

Conclusions:

In a guideline study, to GLP, no irritation potential was observed when ruthenium acetate was applied (under occlusion for 4 hr) to the clipped, intact skin of three rabbits.

Executive summary:

In an OECD Test Guideline 404 study, conducted according to GLP, ruthenium acetate (0.5 g, moistened with 0.5 mL water) was applied (occluded) to the clipped intact skin of 3 New Zealand White rabbits. After 4 hours, the dressings were removed and the treated skin sites were washed and subsequently observed for erythema and oedema 1, 24, 48 and 72 hours.

 

No skin reactions were recorded at any time point in any animal during the 72-hr observation period. The primary dermal irritation index was therefore 0, and ruthenium acetate was classified as a non-irritant to rabbit skin under the conditions of the test.

 

No skin classification, according to EU CLP criteria (EC 1272/2008), is required on the basis of this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22-Nov-1995 to 23-Nov-1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD 405)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, UK

- Age at study initiation: 12-16 weeks

- Weight at study initiation: 2.72 kg

- Housing: singly in a suspended metal cage

- Diet (e.g. ad libitum): Stanrab SQC rabbit diet, ad libitum

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

- Acclimation period: >= 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-18

- Humidity (%): 68-69

- Air changes (per hr): ~15

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

IN-LIFE DATES: From: 22-Nov-1995 To: 23-Nov-1995

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg

- Concentration (if solution): not applicable

VEHICLE
Not applicable

Duration of treatment / exposure:

Test substance not washed from eyes, but presumably physiological mechanisms acted to remove it; eyes examined at 1 and 24 hours

Observation period (in vivo):

24 hours

Number of animals or in vitro replicates:

1

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not done

- Time after start of exposure: not applicable

SCORING SYSTEM: Draize
- cornea (degree of opacity 0-4, area of opacity 1-4, total = 5 x product of scores (max 80))
- iris (0-2, total = 5 x score (max 10))
- conjunctivae (redness 0-3, chemosis 0-4, discharge 0-3, total = 2 x sum of 3 scores (max 20))
- maximum total score 110

TOOL USED TO ASSESS SCORE: light source from a standard ophthalmoscope

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 1 hour

Score:

ca. 17

Max. score:

110

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 hour

Score:

ca. 0

Max. score:

80

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 hour

Score:

ca. 5

Max. score:

10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 hour

Score:

ca. 12

Max. score:

20

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 24 hours

Score:

ca. 63

Max. score:

110

Reversibility:

other: animal humanely killed at 24 hours

Remarks on result:

other: severe irritant

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 hours

Score:

ca. 40

Max. score:

80

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24 hours

Score:

ca. 5

Max. score:

10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24 hours

Score:

ca. 18

Max. score:

20

Irritant / corrosive response data:

At 1 hour: cornea 0 (degree of opacity 0 with dulling of the normal lustre of the corneal surface and black-coloured staining, area of opacity 4), iris 5 (1 with black-coloured staining), conjunctivae 12 (redness 2 with black-coloured staining, chemosis 2, discharge 2 with residual test material around eye), total 17;
At 24 hours: cornea 40 (degree of opacity 2 with black-coloured staining, area of opacity 4), iris 5 (1 with black-coloured staining), conjunctivae 18 (redness 2 with black-coloured staining, chemosis 4, discharge 3 with residual test material around eye)

Other effects:

Signs of pain and discomfort at 24 hours (therefore animal killed for humane reasons)

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

In a guideline eye irritation study, according to GLP, ruthenium acetate (0.1 g) produced severe eye irritation following instillation into the eye of a single rabbit.

Executive summary:

In an in vivo rabbit eye irritation study, conducted in accordance with OECD Test Guideline 405 and to GLP, ruthenium acetate (0.1 g) was instilled into one eye of a single New Zealand white rabbit. Observations of the cornea, iris and conjunctiva were made at 1 and 24 hr after application and the Draize scale was used to assess the degree of irritation.

The total eye irritation score was 17 (out of 110) at 1 hr and 63 (out of 110) at 24 hr. Due to signs of pain and discomfort the animal was killed immediately after the 24-hr time point and no further animals were tested. The 24-hr score indicated that the test substance was a severe eye irritant.

As the results were based on only one rabbit, it is not possible to give a definitive interpretation according to EU CLP criteria (EC 1272/2008). However, it is considered appropriate to classify the test material for serious eye damage (Category 1), as the severe effects observed are not expected to be reversible.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant irritation/corrosion human data were identified.

 

In an OECD Test Guideline 404 study, conducted according to GLP, ruthenium acetate (0.5 g, moistened with 0.5 mL water) was applied (occluded) to the clipped intact skin of 3 New Zealand White rabbits. After 4 hours, the dressings were removed and the treated skin sites were washed and subsequently observed for erythema and oedema 1, 24, 48 and 72 hours. No skin reactions were recorded at any time point in any animal during the 72 -hr observation period. The primary dermal irritation index was therefore 0, and ruthenium acetate was classified as a non-irritant to rabbit skin under the conditions of the test (Allen, 1995b).

 

In an in vivo rabbit eye irritation study, conducted in accordance with OECD Test Guideline 405 and to GLP, ruthenium acetate (0.1 g) was instilled into one eye of a single New Zealand white rabbit. Observations of the cornea, iris and conjunctiva were made at 1 and 24 hr after application and the Draize scale was used to assess the degree of irritation. The total eye irritation score was 17 (out of 110) at 1 hr and 63 (out of 110) at 24 hr. Due to signs of pain and discomfort the animal was killed immediately after the 24-hr time point and no further animals were tested. The 24-hr score indicated that the test substance was a severe eye irritant (Allen, 1995c).

 

No respiratory tract data were identified. A new study was not conducted as it is not a REACH Standard Information Requirement.

Justification for classification or non-classification

Based on the results of the available reliable skin and eye irritation studies (in rabbits), hexakis[mu-(acetato-O:O')]-μ3-oxo-triangulo-triruthenium acetate / ruthenium acetate need not be classified for skin irritation, but should be classified for eye damage (category 1), according to EU CLP criteria (EC 1272/2008).