Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 March 1982 – 24 March 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted according to OECD guidelines, and to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
see below:
Principles of method if other than guideline:
In one group of animals the eye remained unwashed and in the other group the eye was washed 30 seconds after instillation of the test material. The guideline states that “the eyes of the test animals should not be washed for at least 24 hours following instillation of the test substance, except for solids, and in case of immediate corrosive or irritating effects. At 24 hours a washout may be used if considered appropriate.” It goes on to say, in the case of solids, that “if the solid test substance has not been removed from the eye of the test animal by physiological mechanisms at the first observation time point of 1 hour after treatment, the eye may be rinsed with saline or distilled water.”
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): ruthenium (IV) oxide-water (1/n)
- Substance type: black powder
- Physical state: solid
- Purity: no data
- Lot/batch No.: 061151

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire
- Weight at study initiation: 2.02-2.51 kg
- Housing: individually in suspended metal cages
- Diet: ad libitum rabbit diet supplied by J Waring Ltd, Shardlow, Derbyshire
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Air changes (per hr): minimum of 20 air changes/hr
- Photoperiod (hrs dark / hrs light): lighting cycle - 12 hours on / 12 hours off with no daylight

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: Yes, untreated eye
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
“Unwashed group” - Eye not rinsed, therefore possibly up to 7 days
“Washed group” - 30 seconds
Observation period (in vivo):
1, 24, 48 and 72 hrs after application and, if irritation persisted, an additional reading was made at day 7 to assess reversibility or irreversibility.
Number of animals or in vitro replicates:
3/group; sex not specified
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, in one of the groups
- Time after start of exposure: 30 seconds

SCORING SYSTEM: Assessment of damage/irritation in both the washed and unwashed groups was made 1, 24, 48 and 72 hr following instillation of the test material, according to Draize (1965) scores. The test material was then assigned a Group Total Score for Eye Irritation.

TOOL USED TO ASSESS SCORE: standard ophthalmoscope (Keeler). The degree of irritation was further investigated at 24 hr under ultra-violet illumination (Mineralight UVSL-58) preceded by the instillation into the eye of fluorescein B.P.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
other: Group Total Score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 21
Max. score:
195
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
cornea opacity score
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
0
Max. score:
60
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 1
Max. score:
30
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: One rabbit showed slight iridial congestion at the 1 hr observation period, which had disappeared within 24 hrs.
Irritation parameter:
conjunctivae score
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 9
Max. score:
45
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: Minimal to slight conjunctival redness was seen in all three animals at the 1 hr observation time and had completely disappeared by the 72 hr observation time.
Irritation parameter:
chemosis score
Basis:
other: Total score, unwashed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 11
Max. score:
60
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: Conjunctival chemosis was evident in all of the treated animals after 1 hr, but had completely disappeared by 72 hrs.
Irritation parameter:
overall irritation score
Basis:
other: Group Total Score, washed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 15
Max. score:
195
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
cornea opacity score
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 0
Max. score:
60
Reversibility:
other: Not applicable
Irritation parameter:
iris score
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 1
Max. score:
30
Reversibility:
fully reversible within: 24 hrs
Remarks on result:
other: Slight iridial congestion was evident in one rabbit after 1 hr but had completely disappeared by the 24 hr observation time.
Irritation parameter:
conjunctivae score
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 6
Max. score:
45
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: At the 1 hr observation period, minimal to slight conjunctival redness occurred in all of the treated animals. Complete recovery was seen after 72 hrs.
Irritation parameter:
chemosis score
Basis:
other: Total score, washed group
Time point:
other: 1, 24, 48 and 72 hrs
Score:
ca. 8
Max. score:
60
Reversibility:
fully reversible within: 72 hrs
Remarks on result:
other: Conjunctival chemosis was seen in all of the rabbits at the 1 hr observation time and had completely disappeared after 72 hrs.
Irritant / corrosive response data:
In the unwashed group, minimal to slight ocular irritation was seen in 2 of the 3 animals. Minimal (grade 1) to slight (grade 2) conjunctival redness and chemosis was seen in all of the animals at the 1 hr reading and one rabbit also showed slight iridial congestion. All evidence of iridial congestion had disappeared at 24 hrs but minimal chemosis and slight redness persisted in the conjunctiva of one rabbit and minimal redness and minimal chemosis in the remaining two animals. Irritation continued to subside and all lesions had disappeared within 72 hrs.

In the washed group, minimal to slight ocular irritation was noted in all of the treated rabbits. All animals showed minimal to slight conjunctival redness and chemosis at the 1 hr reading, with slight iridial congestion also being seen in one. All iridial congestion had disappeared at the 24 hr reading, but minimal redness and chemosis was still evident in 2 animals. All lesions had disappeared within 72 hrs.
Other effects:
Not reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline eye irritation study, to GLP, ruthenium (IV) oxide hydrate (0.1 g, powdered) produced a group total score of 21 (out of 195) following instillation onto the conjunctival sac of three rabbits and, in a further three rabbits, a group total score of 15 (out of 195) when the test material was washed from the eye 30 seconds following instillation. Although slight irritation was seen, under the EU CLP regulations the test material would not be classified as an eye irritant.
Executive summary:

In an OECD Test Guideline 405 study, ruthenium (IV) oxide hydrate (0.1 g, powdered) was instilled into the conjunctival sac of the right eye of groups of three New Zealand white rabbits and both lids were briefly closed for about 1 second. The left eye remained untreated and acted as the control. In one of the groups, the treated eye was irrigated with 100 ml sterile distilled water, 30 seconds following instillation. Assessment of damage / irritation to the cornea, iris and conjunctiva of the treated eye, using the Draize scale, was made 1, 24, 48 and 72 hr following treatment. If irritation was persistent at 72 hr, an additional reading was made at day 7 in order to assess the reversibility of the effects.

 

These scores were combined to give a Group Total Score for Eye Irritation of 21 (out of 195) for the unwashed eye and 15 (out of 195) for the washed eye. In the unwashed group, observed at 24 hours after instillation, no cornea or iris irritation was reported, although slight (grade 1) to minimal (grade 2) conjunctival redness and chemosis was seen in all three animals. No irritation was seen at 72 hours in any animal (washed or unwashed groups).

 

Based on the results of this study, ruthenium (IV) oxide hydrate should not be classified for eye irritation according to EU CLP criteria (EC 1272/2008).