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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 March - 31 March 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP, with minor deviations (humidity) not anticipated to affect the valididty of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
The relative humidity was outside the stated range on 2 days; this was considered to have no influence on the results of the study
Qualifier:
according to
Guideline:
other: EEC Guideline 92/32/EEC
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): hexahydroxoplatinum(IV)-acid
- Note: The CASRN in this study report corresponds to "diaquatetrahydroxyplatinum". The name dihydrogen hexahydroxyplatinate (synonym hexahydroxoplatinum(IV) acid) corresponds to CAS 51850-20-5. This discrepancy within the study report between CAS and name is inconsequential as these substances would be equivalent from a chemical/toxicological perspective.
- Substance type: Product
- Physical state: Powder
- Analytical purity: >99.9%
- Purity test date: No data
- Lot/batch No.: 8188
- Expiration date of the lot/batch: 1999
- Stability under test conditions:Stable throughout the experimental period
- Storage condition of test material: In a closed container in a refrigerator
- pH: ~6.2

Test animals / tissue source

Species:
rabbit
Strain:
other: White Russian (albino)
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: ASTA Medica AG, D-33790 Halle/Westfalen
- Age at study initiation: 33-49 months
- Weight at study initiation: 2.22-2.94 kg
- Housing: Stainless steel cages with grating floor, type ASTA, size: 48.5x40x36.5 (LxBxH); 1 animal per cage
- Diet (e.g. ad libitum): Approximately 120 g/day/animal of Standard diet, ssniff K, Special diet for rabbits
- Water (e.g. ad libitum): ad libitum from municipal supply
- Acclimation period: at least one day

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 degrees centigrade "constantly"
- Humidity (%): 32-72%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
63.4-85.1 mg (representing a volume of around 0.1 ml) of the test substance was applied into the conjunctival sac of one eye; both lids were briefly closed by gentle finger pressure. Eyes were not rinsed.
Duration of treatment / exposure:
Single application; no rinse was applied during observation period of up to 4 days.
Observation period (in vivo):
3 days for 2 animals; 4 days for one animal.
Observation at 1, 24, 48 and 72 hours after a single application. One animal was observed after an additional 24 hours.
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM: Quantitative and qualitative assessment using the Draize scale (See "Any other information on materials and methods ...", below). An irritation index was calculated from these scores and used to grade irritant effects using a modified method according to Gilman et al.

TOOL USED TO ASSESS SCORE:Cliptrix pencil light; visual assessment, presumably by an experienced technician.

Eyes were examined for corrosive effects; animals were assessed for clinical symptoms that may indicate systemic toxic effects.

Results and discussion

In vivo

Results
Irritation parameter:
other: Irritation index
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours post-application
Score:
6
Max. score:
110
Reversibility:
other: Not applicable
Irritant / corrosive response data:
Some degree of conjunctival redness was seen in all animals. In two, this was slight or moderate and was fully reversible within 3 days; in the remaining animal, moderate to severe redness was reported over 3 days, but was not present by day 4.

Severe conjunctival swelling (chemosis; Draize score 3 of a maximum of 4) was seen in one animal one day following instillation of the test substance; this decreased gradually and was not present by day 4. No conjunctival swelling was seen in the remaining two animals throughout the observation period.

Severe conjunctival discharge (maximum Draize score of 3) was seen in one animal immediately after the test substance was applied, but cleared within 24 hours. In another, abnormal discharge was reported over 2 days following application of the test substance (at 24 hours, this was severe, with the maximum Draize score of 3), but had cleared by day 3. One animal exhibited no abnormal discharge throughout the observation period.

Effects on the iris were seen in one animal at 1 hour (slight circumcorneal hyperemia), and in another animal at 24 and 48 hours (moderate circumcorneal hyperemia). All effects were classified as grade 1 on the Draize scale (where there is a maximum score of 2). In both cases the iris was normal at 3 days. In one animal, the iris was normal throughout the observation period.

No corneal effecs (opacity) were observed in any animal.

Any other information on results incl. tables

No systemic toxic effects were observed.

Draize scoring for ocular lesions:

Cornea

 

a. Opacity-degree of density (Area most dense taken for reading)

 

    No ulceration or opacity                                                                                   0

    Scattered or diffuse areas of opacity (other than slight

    dulling or normal lustre): details of iris clearly visible                                      1

    Easily discernible translucent area: details of iris slightly obscured                 2

    Nacreous area: no details of iris visible: size of pupil barely discernible          3

    Opaque cornea: iris not discernible through the opacity                                   4

 

 

b.  Area of cornea involved

 

One quarter (or less), but not zero                                                                    1

Greater than one quarter, but less than half                                                      2

Greater than half, but less than three quarters                                                  3

Greater than three quarters, up to whole area                                                   4

 

 

Iris

 

a. Values

 

Normal                                                                                                              0

Markedly deepened rugae, congestion, swelling, moderate

circumcorneal hyperaemia: or injection: iris reactive to light

(a sluggish reaction is considered to be an effect)                                           1

Haemorrhage, gross destruction, or no reaction to light.                                 2

Conjunctivae

 

a. Redness (Palpebral and bulbar)

 

Normal                                                                                                              0

Some blood vessels hyperaemic (injected)                                                       1

Diffuse, crimson colour, individual vessels not easily discernible                   2

Diffuse beefy red                                                                                             3

 

 

b.Chemosis

 

Normal                                                                                                              0

Some swelling above normal (includes nictating membrane)                           1

Obvious swelling with partial eversion of lids                                                 2

Swelling with lids about half closed                                                                3

Swelling with lids more than half closed                                                         4

 

 

c. Discharge

 

No discharge                                                                                                    0

Any amount different from normal (does not include small amounts

observed in inner canthus of normal animals)                                                  1

Discharge with moistening of the lids and hairs just adjacent to lids              2

Discharge with moistening of the lids and hairs, on considerable area

around the eye                                                                                                  3

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an OECD Test Guideline 405 in vivo eye irritation study, conducted to GLP, hexahydroxoplatinum(IV) acid produced some transient irritation following instillation of the test material (0.1 ml) into one eye of each of 3 rabbits.
Executive summary:

In an in vivo eye irritation study carried out in accordance with OECD Test Guideline 405, and to GLP, a 0.1 ml aliquot of undiluted hexahydroxoplatinum(IV) acid was instilled into the conjunctival sac of each of three male White Russian rabbits. The other eye was untreated to serve as a control. Following instillation the eyelids were held closed by gentle finger pressure. The ocular response was assessed at 1, 24, 48 and 72 hours. One animal was observed after an additional 24 hours. Corneal opacity, effects on the iris and conjunctival redness, chemosis and discharge were scored according to the Draize numerical scale.

 

No corneal effects (opacity) were observed in any animal. Effects on the iris were seen in one animal at 1 hour (slight circumcorneal hyperemia), and in another animal at 24 and 48 hours (moderate circumcorneal hyperemia). Effects on the conjunctiva were seen in all animals. Notably, in one animal, these were moderate/severe, with maximum scores for discharge and redness reported for at least one time point within the observation period. Indeed, the maximum observed score for conjunctival chemosis (swelling) in this animal was 3 (of a maximum of 4 achievable on the Draize scale). All effects on the iris and conjunctivae were, however, fully reversible within 4 days.

 

The primary irritation index calculated for all animals was 6 (out of 110). The study authors considered the substance to be non-irritant to rabbit eyes. Based on the severe irritation observed in one of the tested animals, it is prudent to classify the test item as an eye irritant (category 2), according to EU CLP criteria (EC 1272/2008).