Tetraammonium decachloro-μ-oxodiruthenate(4-)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

23 March 2012 - 03 August 2012

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:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

The relative humidity was occasionally out of the target range during the study and the acclimatisation period, and the draft report was issued later than indicated in the study plan.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Tetraammonium decachloro-μ- oxodiruthenate

IUPAC Name:

Tetraammonium decachloro-μ- oxodiruthenate

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-)

Constituent 3

Reference substance name:

Tetraammonium decachloro-μ-oxodiruthenate (IV)

IUPAC Name:

Tetraammonium decachloro-μ-oxodiruthenate (IV)

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
- Substance type: Technical product
- Physical state: solid (brown powder)
- Analytical purity: >95%
- Composition of test material, percentage of components: 28.73% ruthenium
-Impurities: Ammonium chloride (0.7%), water (4.0%) and 'metallic impurities' (0.3%).
- Purity test date: 20 July 2015
- Lot/batch No.: 10111
- Expiration date of the lot/batch: 31 July 2012
- Storage condition of test material: Room temperature
- pH: 2.54

The purity analysis was performed in 2015 (after the experimental period, and after the expiration date of the test article). The analytical purity of the substance seems to have in that time decreased from 99% to 95%. This has had no influence on the results of this study, and the compound is still valid with regards to its chemical specifications.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: S&K-LAP Kft., 2173 Kartal, Császár road 135, Hungary
- Age at study initiation: approximately 11 weeks
- Weight at study initiation: 2727 g
- Housing: AAALAC approved metal wire rabbit cages of an open wire structure, placed together to allow some social interaction with rabbit(s) in adjoining cages.
- Diet (e.g. ad libitum): Purina and UNI diet (Lot number: 0030 03 12 and 0060 04 12) for rabbits, produced by AGRIBRANDS Europe Hungary PLC, H-5300 Karcag, Madarasi road, Hungary, ad libitum
- Water (e.g. ad libitum): municipal tap water, as for human consumption, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3°C
- Humidity (%): 24 – 67 % (relative humidity)
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

The test item was instilled into the conjunctival sac of the left eye. The eyelids were held closed for several seconds to prevent the loss of the test item. Rinsing with physiological saline was performed at 24 and 48 hours, and after 1 and 2 weeks.

Observation period (in vivo):

The eyes were examined at 1, 24, 48, 72 hours, 1, 2 and 3 weeks after treatment.

Number of animals or in vitro replicates:

1 male

Details on study design:

Rinsing with physiological saline was performed at 24 and 48 hours, and after 1 and 2 weeks.
Individual reactions of the animal were recorded at each observation time. The nature, severity and duration of all lesions observed were described.
Any clinical signs of toxicity or signs of ill- health during the study were recorded.
At the end of the observation period, the animal was sacrificed by intramuscular injections of CP-Ketamin 10% and CP-Xylazin 2% followed by iv. Euthasol® 40% anaesthesia.

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD guideline no. 405 shown (see below in "Any other information on materials and methods including tables").

TOOL USED TO ASSESS SCORE: apparently visual assessment, presumably by an experienced technician.

Results were presented and interpreted according to Regulation (EC) No 1272/2008, as follows:

Irreversible effects on the eye/serious damage to eyes (Category 1): Substances that have the potential to seriously damage the eyes are classified in Category 1 (irreversible effects on the eye). These observations include animals with grade 4 cornea lesions and other severe reactions (e.g., destruction of cornea) observed at any time during the test, as well as persistent corneal opacity, discoloration of the cornea by a dye substance, adhesion, pannus, and interference with the function of the iris or other effects that impair sight.

Category for irreversible eye effects: If, when applied to the eye of an animal, a substance produces:
— at least in one animal effects on the cornea, iris or conjunctiva that are not expected to reverse or have not fully reversed within an observation period of normally 21 days;
and/or
— at least in 2 of 3 tested animals, a positive response of: corneal opacity ≥ 3 and/or iritis > 1.5 when calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material.

Reversible effects on the eye/irritating to eyes (Category 2): Substances that have the potential to induce reversible eye irritation are classified in Category 2 (irritating to eyes).

Category for reversible eye effects: If, when applied to the eye of an animal, a substance produces (at least in 2 of 3 tested animals) a positive response of:
- corneal opacity ≥ 1 and/or
- iritis ≥ 1, and/or
- conjunctival redness ≥ 2 and/or
- conjunctival oedema (chemosis) ≥ 2

... when calculated as the mean scores following grading at 24, 48 and 72 hours after installation of the test material, and which fully reverses within an observation period of 21 days.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

other: Initial pain reaction

Time point:

other: 0 hr

Score:

2

Remarks on result:

other: Based on this response, 2 additional animals were not treated

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 3 weeks

Results 3

Irritation parameter:

other: Conjunctival discharge

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: Maximum-scoring discharge continued until the end of the observation period of 3 weeks

Results 4

Irritation parameter:

other: Conjunctival redness

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 3 weeks

Remarks on result:

other: The conjunctivae were discoloured black by the test item; redness of 3.00 was assumed for the reading 24 hours after exposure

Results 5

Irritation parameter:

cornea opacity score

Remarks:

opacity

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

not fully reversible within: 3 weeks

Results 6

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72 hours

Score:

0

Max. score:

2

Remarks on result:

other: No effects on the iris were reported

Irritant / corrosive response data:

One hour after the application: Conjunctival discharge (score 3), chemosis (score 2) and corneal opacity (score 2, area 4) were observed. The conjunctivae and the cornea were discoloured black by the test item, therefore observation of the redness of the iris and the conjunctivae was not possible.

At 24 hours after treatment: Conjunctival discharge (score 3), chemosis (score 2) and corneal opacity (score 1, area 4) were observed. The conjunctivae and the cornea remained discoloured black by the test item therefore observation of the redness of the iris and the conjunctivae was not possible.

At 48 and 72 hours after treatment: Conjunctival redness (score 3), discharge
(score 3), chemosis (score 2) and corneal opacity (score 1, area 4) were observed. The conjunctivae and the cornea remained discoloured black by the test item.

At 1 week after treatment: Conjunctival redness (score 2), discharge (score 3), chemosis (score 2) and corneal opacity (score 1, area 4) were observed. Test item residue was observed on the conjunctivae and on the nictitating membrane.

At 2 weeks after treatment: Conjunctival redness (score 2), discharge (score 3) and chemosis (score 2) were observed and corneal opacity (score 1, area 1) was seen in the animal. Test item residue was observed on the conjunctivae and on the nictitating membrane.

At 3 weeks after treatment: Conjunctival redness (score 2), discharge (score 3) and chemosis (score 1) were observed and corneal opacity (score 1, area 1) was seen in the animal. Test item residue was observed on the conjunctivae and on the nictitating membrane.

Other effects:

The conjunctivae and the cornea were discoloured black by the test item; this colouration remained for 72 hours and, at the end of the 3-week observation period, test item residue remained on the conjunctivae and on the nictating membrane.

Any other information on results incl. tables

No mortality was observed during the study.

The body weight and body weight change were considered to be normal with no indication of treatment related effect.

There were no clinical signs observed that could be related to treatment.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

In a guideline study, to GLP, tetraammonium decachloro-μ-oxodiruthenate caused immediate significant conjunctival and corneal irritant effects when applied to the eye of a single male rabbit, which were not fully reversible within 3 weeks.

Executive summary:

In an in vivo eye irritation study carried out in accordance with OECD Test Guideline 405, and to GLP, 0.1 g of tetraammonium decachloro-μ-oxodiruthenate was instilled into the conjunctival sac of the left eye of a single male New Zealand White rabbit. Following instillation the eyelids were held closed for several seconds; rinsing with physiological saline was performed at 24 and 48 hours, and after 1 and 2 weeks. The other eye remained untreated and was used for control purposes. The eyes were examined at 1, 24, 48, 72 hours, as well as 1, 2 and 3 weeks after treatment, and scored according to the Draize system.

Immediate significant conjunctival and corneal irritant effects were observed within one hour that persisted at 72 hours and were not fully reversible within the 3-week observation period.

Based on the results of this study, the substance should be classified for serious eye damage (category 1) according to EU CLP criteria (EC 1272/2008).